Difference between revisions of "Allogeneic HSCT"
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− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|transplant}} | |
− | + | Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all allogeneic hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day before HSCT is day -1, the day of HSCT is day 0, and the day after HSCT is day +1. As with the rest of the HemOnc.org website, the focus here is on regimens used in the treatment of hematologic or oncologic conditions; there are roles for allogeneic HSCT outside of hematology/oncology but these use cases are considered to be out of scope. | |
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− | Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all allogeneic hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day before HSCT is day -1, the day of HSCT is day 0, and the day after HSCT is day +1. | + | <br>These links will take you to highly related pages: |
+ | *'''[[Cellular therapy conditioning regimens]]''' | ||
+ | *'''[[Graft versus host disease|Graft versus host disease (GVHD)]]''' | ||
+ | *'''[[Hepatic veno-occlusive disease|Hepatic veno-occlusive disease (VOD)]]''' | ||
+ | *We have moved [[How I Treat]] articles to a dedicated page. | ||
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=Myeloablative regimens, all lines of therapy= | =Myeloablative regimens, all lines of therapy= | ||
==BuCyTBI {{#subobject:44b691|Regimen=1}}== | ==BuCyTBI {{#subobject:44b691|Regimen=1}}== | ||
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BuCyTBI: '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide, '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | BuCyTBI: '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide, '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ab84cb|Variant=1}}=== | ===Regimen {{#subobject:ab84cb|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM197902153000702 Fefer et al. 1979] |
− | | style="background-color:#ffffbe" |Pilot, | + | | style="background-color:#ffffbe" |Pilot, fewer than 20 pts |
|- | |- | ||
|} | |} | ||
<section begin="ab84cb" /> | <section begin="ab84cb" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Busulfan (Myleran)]] 5 mg/kg IV once on day -6 | |
− | *[[Busulfan (Myleran)]] | + | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -5 & -4 |
− | *[[Cyclophosphamide (Cytoxan)]] | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy|TBI]] 920 rads on day 0 | |
− | *[[External beam radiotherapy|TBI]] | + | ====Immunotherapy==== |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="ab84cb" /> | <section end="ab84cb" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Fefer A, Cheever MA, Thomas ED, Boyd C, Ramberg R, Glucksberg H, Buckner CD, Storb R. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med. 1979 Feb 15;300(7):333-7. [https://doi.org/10.1056/NEJM197902153000702 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/366408/ PubMed] | |
− | #Fefer A, Cheever MA, Thomas ED, Boyd C, Ramberg R, Glucksberg H, Buckner CD, Storb R. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med. 1979 Feb 15;300(7):333-7. [https:// | ||
==Busulfan & Cyclophosphamide {{#subobject:83e07a|Regimen=1}}== | ==Busulfan & Cyclophosphamide {{#subobject:83e07a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide | ||
− | ===Regimen variant #1, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, 3.2 x 4/120 {{#subobject:eeaff3|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | ! style="width: | + | !style="width: 17%"|Study |
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/JCO.2016.70.7349 Kröger et al. 2017 (RICMAC)] |
− | | style="background-color:# | + | |2004-2012 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | + | |[[Allogeneic_HSCT#Busulfan_.26_Fludarabine_2|Bu/Flu RIC allo HSCT]] | |
− | + | | style="background-color:#fee08b" |Might have inferior OS | |
− | + | | | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
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|- | |- | ||
|[https://doi.org/10.1200/jco.2011.40.2362 Lee et al. 2013 (COSAH C-005)] | |[https://doi.org/10.1200/jco.2011.40.2362 Lee et al. 2013 (COSAH C-005)] | ||
Line 84: | Line 69: | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Busulfan_.26_Fludarabine|Busulfan & Fludarabine]] | |[[#Busulfan_.26_Fludarabine|Busulfan & Fludarabine]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint) |
+ | | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(15)00200-4 Rambaldi et al. 2015 (GITMO-AMLR2)] |
|2008-2012 | |2008-2012 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Busulfan_.26_Fludarabine|Busulfan & Fludarabine]] | |[[#Busulfan_.26_Fludarabine|Busulfan & Fludarabine]] | ||
+ | | | ||
| style="background-color:#fc8d59" |Seems to have inferior 1-year non-relapse mortality | | style="background-color:#fc8d59" |Seems to have inferior 1-year non-relapse mortality | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839269/ Zhang et al. 2023] | ||
+ | |2016-01 to 2020-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |[[#Cyclophosphamide_.26_TBI|TBI-Cy]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS24 (primary endpoint)<br>OS24: 76.6% vs 79.4% | ||
+ | | style="background-color:#ffffbf" |Similar NRM | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S2352-3026(22)00375-1 Xuan et al. 2023] | ||
+ | |2016-04-18 to 2019-09-30 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Busulfan.2C_Cyclophosphamide.2C_Decitabine.2C_G-CSF|Busulfan, Cyclophosphamide, Decitabine, G-CSF]] | ||
+ | | style="background-color:#d73027" |Inferior CIR24 | ||
+ | | | ||
|- | |- | ||
|} | |} | ||
<section begin="eeaff3" /> | <section begin="eeaff3" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg) | *[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg) | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg) | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg) | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
*[[Cyclosporine]] | *[[Cyclosporine]] | ||
*[[Methotrexate (MTX)]] "according to the discretion of the attending physician" | *[[Methotrexate (MTX)]] "according to the discretion of the attending physician" | ||
− | + | ====Supportive therapy==== | |
− | ==== | + | *[[Filgrastim (Neupogen)]] 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL |
− | *[[Filgrastim (Neupogen)]] 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/ | + | '''One course''' |
− | + | </div> | |
<section end="eeaff3" /> | <section end="eeaff3" /> | ||
− | ===Regimen variant #3, 16/200 {{#subobject:334af6|Variant=1}}=== | + | </div><br> |
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, 0.8 x 16/120 {{#subobject:ejug23|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1053/bbmt.2002.v8.pm11939604 Andersson et al. 2002] | ||
+ | |1996-06 to 1997-12 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | | | ||
+ | | | ||
+ | | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.23.00101 Ling et al. 2023] | ||
+ | |2015-11-20 to 2019-09-30 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Busulfan_.26_Fludarabine|BuFlu]] | ||
+ | | | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior TRM12 | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="ejug23" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Busulfan (Myleran)]] 0.8 mg/kg IV four times per per day on days -7 to -4 (total dose: 12.8 mg/kg) | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="ejug23" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 1 x 16/200 {{#subobject:334af6|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 40%; text-align:center;" | ||
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198312013092202 Santos et al. 1983] |
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
<section begin="334af6" /> | <section begin="334af6" /> | ||
− | |||
''Note: the day of allogeneic stem cell transplant is not specified in the protocol.'' | ''Note: the day of allogeneic stem cell transplant is not specified in the protocol.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Busulfan (Myleran)]] 1 mg/kg IV every 6 hours on days 1 to 4 (total dose: 16 mg/kg) | *[[Busulfan (Myleran)]] 1 mg/kg IV every 6 hours on days 1 to 4 (total dose: 16 mg/kg) | ||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days 5 to 8 (total dose: 200 mg/kg) | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days 5 to 8 (total dose: 200 mg/kg) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="334af6" /> | <section end="334af6" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
+ | #Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. [https://doi.org/10.1056/NEJM198312013092202 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/6355849/ PubMed] | ||
+ | #Andersson BS, Kashyap A, Gian V, Wingard JR, Fernandez H, Cagnoni PJ, Jones RB, Tarantolo S, Hu WW, Blume KG, Forman SJ, Champlin RE. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transplant. 2002;8(3):145-54. [https://doi.org/10.1053/bbmt.2002.v8.pm11939604 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11939604/ PubMed] | ||
+ | #'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23129746/ PubMed] [https://clinicaltrials.gov/study/NCT00774280 NCT00774280] | ||
+ | #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297/ PubMed] [https://clinicaltrials.gov/study/NCT01191957 NCT01191957] | ||
+ | # '''RICMAC:''' Kröger N, Iacobelli S, Franke GN, Platzbecker U, Uddin R, Hübel K, Scheid C, Weber T, Robin M, Stelljes M, Afanasyev B, Heim D, Deliliers GL, Onida F, Dreger P, Pini M, Guidi S, Volin L, Günther A, Bethge W, Poiré X, Kobbe G, van Os M, Brand R, de Witte T. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial). J Clin Oncol. 2017 Jul 1;35(19):2157-2164. Epub 2017 May 2. [https://doi.org/10.1200/JCO.2016.70.7349 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28463633/ PubMed] [https://clinicaltrials.gov/study/NCT01203228 NCT01203228] | ||
+ | #Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. [https://doi.org/10.1200/JCO.22.00767 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839269/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36084276/ PubMed] [https://clinicaltrials.gov/study/NCT02670252 NCT02670252] | ||
+ | #Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. [https://doi.org/10.1016/S2352-3026(22)00375-1 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36702138/ PubMed] [https://clinicaltrials.gov/study/NCT02744742 NCT02744742] | ||
+ | #Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. [https://doi.org/10.1200/jco.23.00101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37335960/ PubMed] [https://clinicaltrials.gov/study/NCT02487069 NCT02487069] | ||
− | + | ==Busulfan, Cyclophosphamide, Decitabine, G-CSF {{#subobject:4ye07a|Regimen=1}}== | |
− | # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen {{#subobject:57gch8|Variant=1}}=== | |
− | # | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S2352-3026(22)00375-1 Xuan et al. 2023] | ||
+ | |2016-04-18 to 2019-09-30 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Busulfan_.26_Cyclophosphamide|BuCy]] | ||
+ | | style="background-color:#1a9850" |Superior CIR24 (primary endpoint)<br>CIR24: 10.9% vs 24.8%<br>(HR 0.39, 95% CI 0.19-0.79) | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="57gch8" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg) | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 (total dose: 120 mg/kg) | ||
+ | *[[Decitabine (Dacogen)]] 20 mg/m<sup>2</sup> IV once per day on days -14 to -10 | ||
+ | ====Growth factor therapy==== | ||
+ | *[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg once per day on days -17 to -10 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="57gch8" /> | ||
+ | </div> | ||
+ | ===References=== | ||
+ | #Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. [https://doi.org/10.1016/S2352-3026(22)00375-1 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36702138/ PubMed] [https://clinicaltrials.gov/study/NCT02744742 NCT02744742] | ||
==Busulfan & Fludarabine {{#subobject:576283|Regimen=1}}== | ==Busulfan & Fludarabine {{#subobject:576283|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine | ||
<br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan | <br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen variant #1 {{#subobject: | + | ===Regimen variant #1 {{#subobject:d41ng5|Variant=1}}=== |
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 17%"|Study |
− | !style="width: | + | !style="width: 15%"|Dates of enrollment |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 17%"|Comparator |
− | !style="width: | + | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.23.00101 Ling et al. 2023] | ||
+ | |2015-11-20 to 2019-09-30 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | ||
+ | |[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | ||
+ | | | ||
+ | | style="background-color:#91cf60" |Seems to have superior TRMM12 (primary endpoint) | ||
|- | |- | ||
+ | |} | ||
+ | '''Diseases Studied: [[Acute myeloid leukemia]]''' | ||
+ | <section begin="d41ng5" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Busulfan (Myleran)]] 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3 | ||
+ | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -7 to -3 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="d41ng5" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:d415a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(15)00200-4 Rambaldi et al. 2015 (GITMO-AMLR2)] |
|2008-2012 | |2008-2012 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | |[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | ||
− | | style="background-color:# | + | | |
+ | | style="background-color:#91cf60" |Seems to have superior NRM12 (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | '''Diseases Studied: [[Acute myeloid leukemia]]''' | + | '''Diseases Studied: [[Acute myeloid leukemia]]'''<br> |
− | |||
'''Graft types studied''': Bone Marrow, Mobilized Peripheral Blood Stem Cells | '''Graft types studied''': Bone Marrow, Mobilized Peripheral Blood Stem Cells | ||
<section begin="d415a" /> | <section begin="d415a" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Busulfan (Myleran)]] 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3 | *[[Busulfan (Myleran)]] 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3 | ||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -3 | ||
− | + | ====GVHD prophylaxis, pre-transplant==== | |
− | ==== | + | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] by the following donor-based criteria: |
− | + | **Matched unrelated donors: 0.5 mg/kg IV once on day -3, then 2 mg/kg IV once on day -2, then 2.5 mg/kg IV once on day -1 | |
− | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] by the following criteria: | + | **Mismatched donors: total ATG dose could be increased to 7.5 mg/kg |
− | ** | + | ====Immunotherapy==== |
− | ** | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis, post-transplant==== | |
− | ====GVHD prophylaxis==== | ||
− | |||
*[[Cyclosporine]] | *[[Cyclosporine]] | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="d415a" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #3 {{#subobject:d415b|Variant=1}}=== | |
− | ===Regimen variant # | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 185: | Line 294: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ Andersson et al. 2008] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ Andersson et al. 2008] | ||
− | |1997- | + | |1997-2005 |
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
− | | style="background-color:# | + | | style="background-color:#91cf60" |Suggested improved outcomes, but shorter follow up |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209101/ Kanakry et al. 2014 (J0844)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209101/ Kanakry et al. 2014 (J0844)] | ||
Line 196: | Line 305: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4797026/ Mielcarek et al. 2016 (FHCC 2541.00)] |
|2011-2013 | |2011-2013 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
− | | style="background-color:#d3d3d3" | | + | | style="background-color:#d3d3d3" |- |
|} | |} | ||
− | + | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Acute lymphocytic leukemia]], [[Chronic myeloid leukemia]], [[Non-Hodgkin lymphoma]]'''<br> | |
− | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Acute lymphocytic leukemia]], [[Chronic | ||
− | |||
'''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells | '''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells | ||
<section begin="d415b" /> | <section begin="d415b" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Busulfan (Myleran)]] 130 mg/m<sup>2</sup> IV over 3 hours once per day on days -6 to -3 | |
− | *[[Busulfan (Myleran)]] 130 mg/m<sup>2</sup> IV over 3 hours once per day on days -6 to -3 | ||
**Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels | **Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels | ||
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days -6 to -3, '''given first''' | *[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> IV over 60 minutes once per day on days -6 to -3, '''given first''' | ||
− | + | ====GVHD prophylaxis, pre-transplant==== | |
− | ==== | + | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] by the following donor-based criteria: |
− | + | **Unrelated or mismatched donors: 0.5 mg/kg IV once on day -3, then 1.5 mg/kg IV once on day -2, then 2 mg/kg IV once on day -1 | |
− | * | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
− | ====GVHD prophylaxis==== | + | ====GVHD prophylaxis, post-transplant==== |
<nowiki>#</nowiki>1 Tacrolimus & methotrexate based (Andersson et al.) | <nowiki>#</nowiki>1 Tacrolimus & methotrexate based (Andersson et al.) | ||
− | |||
*[[Tacrolimus (Prograf)]] | *[[Tacrolimus (Prograf)]] | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
− | + | ====Supportive therapy==== | |
− | ==== | + | *All patients received [[Filgrastim (Neupogen)]] SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 x 10<sup>9</sup>/L for three days |
− | *All patients received [[Filgrastim (Neupogen)]] SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 | ||
*[[Phenytoin (Dilantin)]] prophylaxis used during and for one day after IV busulfan | *[[Phenytoin (Dilantin)]] prophylaxis used during and for one day after IV busulfan | ||
− | + | <nowiki>#</nowiki>2 Post-Transplant Cy based (Kanakry et al. and FHCC 2541.00) | |
− | <nowiki>#</nowiki>2 Post-Transplant Cy based (Kanakry et al. and | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts) | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts) | ||
− | *± [[Cyclosporine]] intravenous loading dose of CSP was given on day 5, followed by subsequent twice | + | *± [[Cyclosporine]] intravenous loading dose of CSP was given on day 5, followed by subsequent twice per day dosing adjusted to maintain whole blood trough at 120 to 360 ng/mL. In abscence of GVHD Cyclosporine was tapered from day +56 through day +126 (used in FHCC 2541.00 with PBSCT grafts) |
− | ==== | + | ====Supportive therapy==== |
*[[Mesna (Mesnex)]] given with cyclophosphamide | *[[Mesna (Mesnex)]] given with cyclophosphamide | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="d415b" /> | <section end="d415b" /> | ||
− | + | </div><br> | |
− | ===Regimen variant # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | ===Regimen variant #4 {{#subobject:d415c|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 247: | Line 354: | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | |[[#Busulfan_.26_Cyclophosphamide|Busulfan & Cyclophosphamide]] | ||
− | | style="background-color:#fc8d59" |Seems to have inferior OS | + | | style="background-color:#fc8d59" |Seems to have inferior OS (secondary endpoint) |
|- | |- | ||
|} | |} | ||
− | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Acute lymphocytic leukemia]], [[Chronic | + | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Acute lymphocytic leukemia]], [[Chronic myeloid leukemia]], [[Myelofibrosis]]'''<br> |
− | |||
'''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells | '''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells | ||
<section begin="d415c" /> | <section begin="d415c" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -7 to -4, '''given first on days overlapping with fludarabine''' (total dose: 12.8 mg/kg) | *[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -7 to -4, '''given first on days overlapping with fludarabine''' (total dose: 12.8 mg/kg) | ||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2, '''given second on days overlapping with busulfan''' | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2, '''given second on days overlapping with busulfan''' | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
*"[[Cyclosporine]] | *"[[Cyclosporine]] | ||
*[[Methotrexate (MTX)]] "according to the discretion of the attending physician" | *[[Methotrexate (MTX)]] "according to the discretion of the attending physician" | ||
− | ==== | + | ====Supportive therapy==== |
− | *[[Filgrastim (Neupogen)]] 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/ | + | *[[Filgrastim (Neupogen)]] 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL |
+ | '''One course''' | ||
+ | </div> | ||
<section end="d415c" /> | <section end="d415c" /> | ||
− | ===Regimen variant # | + | </div><br> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | ! style="width: | + | ===Regimen variant #5 {{#subobject:6eb66d|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1053/bbmt.2002.v8.pm12374451 Russell et al. 2002] |
+ | |1999-2001 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Chronic | + | '''Diseases Studied: [[Acute myeloid leukemia]], [[Myelodysplastic syndrome]], [[Chronic myeloid leukemia]], [[Chronic lymphocytic leukemia]], [[Non-Hodgkin lymphoma]], [[Hypereosinophilic syndrome]]'''<br> |
− | |||
'''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow or Mobilized Peripheral Blood Stem Cells | '''Graft types studied''': Matched Related / Unrelated Donor Bone Marrow or Mobilized Peripheral Blood Stem Cells | ||
<section begin="6eb66d" /> | <section begin="6eb66d" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Busulfan (Myleran)]] 3.2 mg/kg (ideal body weight) IV over 3 hours once per day on days -5 to -2 | *[[Busulfan (Myleran)]] 3.2 mg/kg (ideal body weight) IV over 3 hours once per day on days -5 to -2 | ||
*[[Fludarabine (Fludara)]] 50 mg/m<sup>2</sup> IV once per day on days -6 to -2 | *[[Fludarabine (Fludara)]] 50 mg/m<sup>2</sup> IV once per day on days -6 to -2 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis==== | |
*[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 0.5 mg/kg IV once on day -2, then 2 mg/kg IV once per day on days -1 & 0 (total dose of 4.5 mg/kg) | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 0.5 mg/kg IV once on day -2, then 2 mg/kg IV once per day on days -1 & 0 (total dose of 4.5 mg/kg) | ||
− | |||
− | |||
− | |||
*[[Cyclosporine]] IV or PO twice per day, with doses adjusted to maintain cyclosporine levels of 150 to 400 umol/L | *[[Cyclosporine]] IV or PO twice per day, with doses adjusted to maintain cyclosporine levels of 150 to 400 umol/L | ||
− | *[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> (route not specified) once on day 1, then 10 mg/m<sup>2</sup> (route not specified) once per day on days 3, 6, 11 | + | *[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> (route not specified) once on day 1, then 10 mg/m<sup>2</sup> (route not specified) once per day on days +3, +6, +11 |
− | ==== | + | ====Supportive therapy==== |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 5 mg started 24 hours after each dose of methotrexate and continued every 6 hours until 12 hours before the next dose of methotrexate |
*[[Phenytoin (Dilantin)]] "loading" PO/IV, dosed to maintain therapeutic levels of 40 to 80 umol/L on days -5 to -2 | *[[Phenytoin (Dilantin)]] "loading" PO/IV, dosed to maintain therapeutic levels of 40 to 80 umol/L on days -5 to -2 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="6eb66d" /> | <section end="6eb66d" /> | ||
− | + | </div> | |
===References=== | ===References=== | ||
− | + | #Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8(9):468-76. [https://doi.org/10.1053/bbmt.2002.v8.pm12374451 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12374451/ PubMed] | |
− | #Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [ | + | #de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004 Aug 1;104(3):857-64. Epub 2004 Apr 8. [https://doi.org/10.1182/blood-2004-02-0414 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15073038/ PubMed] |
− | #'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] ''' | + | #Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. [https://doi.org/10.1016/j.bbmt.2008.03.009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230823/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18489993/ PubMed] |
− | #'''J0844:''' Kanakry CG, O'Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, Mielcarek M, Champlin RE, Jones RJ, Thall PF, Andersson BS, Luznik L. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497-505. Epub 2014 Sep 29. [https://doi.org/10.1200/JCO.2013.54.0625 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209101/ link to PMC article] ''' | + | #'''COSAH C-005:''' Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. [https://doi.org/10.1200/jco.2011.40.2362 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23129746/ PubMed] [https://clinicaltrials.gov/study/NCT00774280 NCT00774280] |
− | #Mielcarek M, Furlong T, O'Donnell PV, Storer BE, McCune JS, Storb R, Carpenter PA, Flowers ME, Appelbaum FR, Martin PJ. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502-8. [ | + | #'''J0844:''' Kanakry CG, O'Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, Mielcarek M, Champlin RE, Jones RJ, Thall PF, Andersson BS, Luznik L. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497-505. Epub 2014 Sep 29. [https://doi.org/10.1200/JCO.2013.54.0625 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209101/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25267759/ PubMed] [https://clinicaltrials.gov/study/NCT00809276 NCT00809276] |
− | #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https:// | + | #'''FHCC 2541.00:''' Mielcarek M, Furlong T, O'Donnell PV, Storer BE, McCune JS, Storb R, Carpenter PA, Flowers ME, Appelbaum FR, Martin PJ. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502-8. Epub 2016 Jan 13. [https://doi.org/10.1182/blood-2015-10-672071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4797026/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26764356/ PubMed] [https://clinicaltrials.gov/study/NCT01427881 NCT01427881] |
− | # | + | #'''GITMO-AMLR2:''' Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. [https://doi.org/10.1016/S1470-2045(15)00200-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26429297/ PubMed] [https://clinicaltrials.gov/study/NCT01191957 NCT01191957] |
+ | #'''MDACC 2011-0628:''' Andersson BS, Thall PF, Ma J, Valdez BC, Bassett R Jr, Chen J, Ahmed S, Alousi A, Bashir Q, Ciurea S, Gulbis A, Cool R, Kawedia J, Hosing C, Kebriaei P, Kornblau S, Myers A, Oran B, Rezvani K, Shah N, Shpall E, Parmar S, Popat UR, Nieto Y, Champlin RE. A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation. Bone Marrow Transplant. 2022 Aug;57(8):1295-1303. Epub 2022 May 24. [https://doi.org/10.1038/s41409-022-01705-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9352570/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35610308/ PubMed] [https://clinicaltrials.gov/study/NCT01471444 NCT01471444] | ||
+ | #Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. [https://doi.org/10.1200/jco.23.00101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37335960/ PubMed] [https://clinicaltrials.gov/study/NCT02487069 NCT02487069] | ||
==Cyclophosphamide & TBI {{#subobject:a9f7e8|Regimen=1}}== | ==Cyclophosphamide & TBI {{#subobject:a9f7e8|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <br>TBI-CY: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation & '''<u>Cy</u>'''clophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:6ca28d|Variant=1}}=== | ===Regimen {{#subobject:6ca28d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 320: | Line 431: | ||
!style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | !style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/archinte.1973.03650080121024 Rudolph et al. 1973] |
|1968-1970 | |1968-1970 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 327: | Line 438: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198201143060202 Fefer et al. 1982] |
|1971-1980 | |1971-1980 | ||
− | | style="background-color:#ffffbe" |Non-randomized, | + | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V54.2.468.468 Thomas et al. 1979] |
|1976-1977 | |1976-1977 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 341: | Line 452: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198005083021901 Blume et al. 1980] |
|1976-1979 | |1976-1979 | ||
− | | style="background-color:#ffffbe" |Non-randomized, | + | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198110083051502 Johnson et al. 1981] |
|1976-1980 | |1976-1980 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 355: | Line 466: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198712243172602 Brochstein et al. 1987] |
|1979-1985 | |1979-1985 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 362: | Line 473: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198601233140403 Goldman et al. 1986] |
|1981-1984 | |1981-1984 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 369: | Line 480: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198708203170801 Kersey et al. 1987] |
|1982-1985 | |1982-1985 | ||
| style="background-color:#1a9851" |Quasi-randomized | | style="background-color:#1a9851" |Quasi-randomized | ||
Line 376: | Line 487: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199804023381405 Hansen et al. 1998] |
|1985-1994 | |1985-1994 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 387: | Line 498: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|Chemotherapy or Auto HSCT | |Chemotherapy or Auto HSCT | ||
− | | style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199501263320403 Zittoun et al. 1995] |
|1986-1993 | |1986-1993 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 399: | Line 510: | ||
|[https://doi.org/10.1200/jco.2004.10.050 Thomas et al. 2004 (LALA-94)] | |[https://doi.org/10.1200/jco.2004.10.050 Thomas et al. 2004 (LALA-94)] | ||
|1994-2002 | |1994-2002 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70349-2 Bornhäuser et al. 2012 (9005-2003)] |
|2004-2009 | |2004-2009 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 410: | Line 521: | ||
| | | | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of NRM | | style="background-color:#ffffbf" |Did not meet primary endpoint of NRM | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839269/ Zhang et al. 2023] | ||
+ | |2016-01 to 2020-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Busulfan_.26_Cyclophosphamide|BuCy]] | ||
+ | | style="background-color:#eeee01" |Non-inferior OS24 | ||
+ | | style="background-color:#ffffbf" |Similar NRM | ||
|- | |- | ||
|} | |} | ||
<section begin="6ca28d" /> | <section begin="6ca28d" /> | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ''Details in the manuscripts are limited.'' | + | ''Details in most of the manuscripts are limited.'' |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | |
− | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation]] by the following study-specific criteria: | |
− | *[[External_beam_radiotherapy|Total body irradiation]] | + | **Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total) |
+ | **Other studies: 10 to 1200 cGy total | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="6ca28d" /> | <section end="6ca28d" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Rudolph RH, Fefer A, Thomas ED, Buckner CD, Clift RA, Storb R. Isogeneic marrow grafts for hematologic malignancy in man. Arch Intern Med. 1973 Aug;132(2):279-85. [https://doi.org/10.1001/archinte.1973.03650080121024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4268940/ PubMed] | |
− | #Rudolph RH, Fefer A, Thomas ED, Buckner CD, Clift RA, Storb R. Isogeneic marrow grafts for hematologic malignancy in man. Arch Intern Med. 1973 Aug;132(2):279-85. [https:// | + | ##'''Update:''' Fefer A, Einstein AB, Thomas ED, Buckner CD, Clift RA, Glucksberg H, Neiman PE, Storb R. Bone-marrow transplantation for hematologic neoplasia in 16 patients with identical twins. N Engl J Med. 1974 Jun 20;290(25):1389-93. [https://doi.org/10.1056/NEJM197406202902501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4597885/ PubMed] |
− | ##'''Update:''' Fefer A, Einstein AB, Thomas ED, Buckner CD, Clift RA, Glucksberg H, Neiman PE, Storb R. Bone-marrow transplantation for hematologic neoplasia in 16 patients with identical twins. N Engl J Med. 1974 Jun 20;290(25):1389-93. [https:// | + | #Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. [https://doi.org/10.1182/blood.V54.2.468.468 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/378292/ PubMed] |
− | #Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. [ | + | #Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https://doi.org/10.1056/NEJM198005083021901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6245359/ PubMed] |
− | #Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. [https:// | + | #Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. [https://doi.org/10.1056/NEJM198110083051502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7024804/ PubMed] |
− | #Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. [https:// | + | #Fefer A, Cheever MA, Greenberg PD, Appelbaum FR, Boyd CN, Buckner CD, Kaplan HG, Ramberg R, Sanders JE, Storb R, Thomas ED. Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins. N Engl J Med. 1982 Jan 14;306(2):63-8. [https://doi.org/10.1056/NEJM198201143060202 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7031474/ PubMed] |
− | #Fefer A, Cheever MA, Greenberg PD, Appelbaum FR, Boyd CN, Buckner CD, Kaplan HG, Ramberg R, Sanders JE, Storb R, Thomas ED. Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins. N Engl J Med. 1982 Jan 14;306(2):63-8. [https:// | + | #Goldman JM, Apperley JF, Jones L, Marcus R, Goolden AW, Batchelor R, Hale G, Waldmann H, Reid CD, Hows J, Gordon-Smith E, Catovsky D, Galton DAG. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med. 1986 Jan 23;314(4):202-7. [https://pubmed.ncbi.nlm.nih.gov/3510388/ PubMed] |
− | #Goldman JM, Apperley JF, Jones L, Marcus R, Goolden AW, Batchelor R, Hale G, Waldmann H, Reid CD, Hows J, Gordon-Smith E, Catovsky D, Galton DAG. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med. 1986 Jan 23;314(4):202-7. [https://pubmed.ncbi.nlm.nih.gov/3510388 PubMed] | + | #Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. [https://doi.org/10.1056/NEJM198708203170801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3302708/ PubMed] |
− | #Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. [https:// | + | #Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. [https://doi.org/10.1056/NEJM198712243172602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3317056/ PubMed] |
− | #Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. [https:// | + | #'''LALA 87:''' Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, Dreyfus F, Fiere D; French Group of Therapy of Adult Acute Lymphoblastic Leukemia. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol. 1994 Dec;12(12):2580-7. [https://doi.org/10.1200/JCO.1994.12.12.2580 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7989932/ PubMed] |
− | #'''LALA 87:''' Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, Dreyfus F, Fiere D; French Group of Therapy of Adult Acute Lymphoblastic Leukemia. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol. 1994 Dec;12(12):2580-7. [https://doi.org/10.1200/JCO.1994.12.12.2580 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7989932 PubMed] | + | ##'''Update:''' Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C, Lepage E, Thomas X, Fière D. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation: a follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am. 2000 Dec;14(6):1353-66. [https://doi.org/10.1016/s0889-8588(05)70190-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11147227/ PubMed] |
− | ##'''Update:''' Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C, Lepage E, Thomas X, Fière D. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation: a follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am. 2000 Dec;14(6):1353-66. [https://doi.org/10.1016/s0889-8588(05)70190-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11147227 PubMed] | + | #Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https://doi.org/10.1056/NEJM199501263320403 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7808487/ PubMed] |
− | #Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; [[Study_Groups#EORTC|EORTC]]; Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. [https:// | + | #Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. [https://doi.org/10.1056/NEJM199804023381405 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9521984/ PubMed] |
− | #Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. [https:// | + | #'''LALA-94:''' Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, Fiere D. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86. Epub 2004 Sep 7. [https://doi.org/10.1200/jco.2004.10.050 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15353542/ PubMed] [https://clinicaltrials.gov/study/NCT00002700 NCT00002700] |
− | #'''LALA-94:''' Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, Fiere D. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86. Epub 2004 Sep 7. [https://doi.org/10.1200/jco.2004.10.050 link to original article] ''' | + | ##'''Update:''' Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J; Swiss Group for Clinical Cancer Research. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006 Dec;20(12):2155-61. Epub 2006 Oct 12. [https://doi.org/10.1038/sj.leu.2404420 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17039234/ PubMed] |
− | + | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22959335/ PubMed] [https://clinicaltrials.gov/study/NCT00150878 NCT00150878] | |
− | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https:// | + | #'''Retrospective:''' Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. [https://doi.org/10.1182/blood-2013-07-514448 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854108/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24065243/ PubMed] |
− | + | #Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. [https://doi.org/10.1200/JCO.22.00767 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839269/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36084276/ PubMed] [https://clinicaltrials.gov/study/NCT02670252 NCT02670252] | |
− | # | + | #'''SWOG S9920:''' [https://clinicaltrials.gov/study/NCT00005866 NCT00005866] |
− | |||
==Etoposide & TBI {{#subobject:b389e1|Regimen=1}}== | ==Etoposide & TBI {{#subobject:b389e1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, weight-based etoposide {{#subobject:45f841|Variant=1}}=== | ===Regimen variant #1, weight-based etoposide {{#subobject:45f841|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0140-6736(05)66998-x Balduzzi et al. 2005] |
|1995-2000 | |1995-2000 | ||
| style="background-color:#1a9851" |Quasi-randomized | | style="background-color:#1a9851" |Quasi-randomized | ||
Line 473: | Line 591: | ||
''This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CR1.'' | ''This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CR1.'' | ||
<section begin="45f841" /> | <section begin="45f841" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 60 mg/kg (maximum dose of 3600 mg) IV once on day -3 | *[[Etoposide (Vepesid)]] 60 mg/kg (maximum dose of 3600 mg) IV once on day -3 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy twice per day in 6 fractions on days -6 to -4 with lung shielding at 1000 cGy (total dose: 1200 cGy) | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="45f841" /> | <section end="45f841" /> | ||
− | + | </div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, BSA-based etoposide {{#subobject:45u7g1|Variant=1}}=== | ===Regimen variant #2, BSA-based etoposide {{#subobject:45u7g1|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078415/ Peters et al. 2020 (FORUM)] |
|2013-2018 | |2013-2018 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |1a. [[#Busulfan.2C_Fludarabine.2C_Thiotepa_999|Busulfan, Fludarabine, Thiotepa]]<br>1b. [[#Fludarabine.2C_Thiotepa.2C_Treosulfan_999|Fludarabine, Thiotepa, Treosulfan]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint) |
|- | |- | ||
|} | |} | ||
''This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CMR.'' | ''This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CMR.'' | ||
<section begin="45u7g1" /> | <section begin="45u7g1" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 1800 mg/m<sup>2</sup> (maximum dose of 3600 mg) IV once on day -3 | *[[Etoposide (Vepesid)]] 1800 mg/m<sup>2</sup> (maximum dose of 3600 mg) IV once on day -3 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy twice per day in 6 fractions on days -6 to -4 with lung shielding at 1000 cGy (total dose: 1200 cGy) | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="45u7g1" /> | <section end="45u7g1" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen variant #3, | + | ===Regimen variant #3, 1320 cGy {{#subobject:e4216b|Variant=1}}=== |
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2005-04-1623 Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)] |
− | | style="background-color:#91cf61" |Non-randomized | + | |1993-2003 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
''Note: this is the same preparative regimen used for autologous transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.'' | ''Note: this is the same preparative regimen used for autologous transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.'' | ||
<section begin="e4216b" /> | <section begin="e4216b" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 60 mg/kg IV once on day -3 | *[[Etoposide (Vepesid)]] 60 mg/kg IV once on day -3 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 220 cGy twice per day in 6 fractions on days -6 to -4 (total dose: 1320 cGy) | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="e4216b" /> | <section end="e4216b" /> | ||
− | + | </div> | |
===References=== | ===References=== | ||
− | + | #Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. [https://doi.org/10.1016/s0140-6736(05)66998-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16112299/ PubMed] | |
− | #Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. [https:// | + | #'''MRC UKALL XII/ECOG E2993:''' Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. [https://doi.org/10.1182/blood-2005-04-1623 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16105981/ PubMed] [https://clinicaltrials.gov/study/NCT00002514 NCT00002514] |
− | #'''MRC UKALL XII/ECOG E2993:''' Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. [ | + | ##'''Update:''' Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. [https://doi.org/10.1182/blood-2007-10-116582 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18048644/ PubMed] |
− | ##'''Update:''' Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. [ | + | ##'''Update:''' Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. [https://doi.org/10.1182/blood-2009-01-199380 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188540/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19244158/ PubMed] |
− | ##'''Update:''' Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. [ | + | ##'''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [https://doi.org/10.1182/blood-2013-09-529008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24277073/ PubMed] |
− | ##'''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [ | + | #'''ALL-SCT-BFM-2003:''' Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. [https://doi.org/10.1200/jco.2014.58.9747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25753432/ PubMed] [https://clinicaltrials.gov/study/NCT01423747 NCT01423747] |
− | #'''ALL-SCT-BFM-2003:''' Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. [https://doi.org/10.1200/jco.2014.58.9747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25753432 PubMed] NCT01423747 | + | #'''FORUM:''' Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Güngör T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M, von Stackelberg A, Balduzzi A, Corbacioglu S, Bader P; IBFM Study Group; IntReALL Study Group; I-BFM SCT Study Group; EBMT Paediatric Diseases Working Party. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.02529 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078415/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33332189/ PubMed] [https://clinicaltrials.gov/study/NCT01949129 NCT01949129] |
− | #'''FORUM:''' Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Güngör T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M, von Stackelberg A, Balduzzi A, Corbacioglu S, Bader P; IBFM Study Group; IntReALL Study Group; I-BFM SCT Study Group; EBMT Paediatric Diseases Working Party. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.02529 link to original article] ''' | ||
− | |||
==Fludarabine, Busulfan, Cyclophosphamide {{#subobject:84acb0|Regimen=1}}== | ==Fludarabine, Busulfan, Cyclophosphamide {{#subobject:84acb0|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide | FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide | ||
− | ===Regimen {{#subobject:bfe434|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, oral {{#subobject:bfe434|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)] |
+ | |2004-06-16 to 2009-03-24 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
Line 555: | Line 681: | ||
''This is described by the authors as a lymphoma-directed myeloablative conditioning regimen'' | ''This is described by the authors as a lymphoma-directed myeloablative conditioning regimen'' | ||
<section begin="bfe434" /> | <section begin="bfe434" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup>/day IV on days -8 to -4 | *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup>/day IV on days -8 to -4 | ||
*[[Busulfan (Myleran)]] 4 mg/kg/day PO on days -6 to -4 | *[[Busulfan (Myleran)]] 4 mg/kg/day PO on days -6 to -4 | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg/day IV on days -3 and -2 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg/day IV on days -3 and -2 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis==== | |
*[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2 mg/kg IV from day -3 to -1 (''unclear if this is a total dose or a daily dose'') | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2 mg/kg IV from day -3 to -1 (''unclear if this is a total dose or a daily dose'') | ||
**Option also to use [[Antithymocyte globulin, rabbit ATG (Grafalon)|ATG-Fresenius S]] at a higher dose of 10 mg/kg | **Option also to use [[Antithymocyte globulin, rabbit ATG (Grafalon)|ATG-Fresenius S]] at a higher dose of 10 mg/kg | ||
− | + | *[[Tacrolimus (Prograf)]] 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD | |
+ | *[[Mycophenolate mofetil (CellCept)]] 1000 mg (route not specified) twice per day from day +1 to +28 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="bfe434" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, intravenous {{#subobject:bfe434|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)] | ||
+ | |2004-06-16 to 2009-03-24 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | ''This is described by the authors as a lymphoma-directed myeloablative conditioning regimen'' | ||
+ | <section begin="bfe435" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup>/day IV on days -8 to -4 | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg/day IV on days -6 to -4 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg/day IV on days -3 and -2 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | + | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2 mg/kg IV from day -3 to -1 (''unclear if this is a total dose or a daily dose'') | |
+ | **Option also to use [[Antithymocyte globulin, rabbit ATG (Grafalon)|ATG-Fresenius S]] at a higher dose of 10 mg/kg | ||
*[[Tacrolimus (Prograf)]] 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD | *[[Tacrolimus (Prograf)]] 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD | ||
*[[Mycophenolate mofetil (CellCept)]] 1000 mg (route not specified) twice per day from day +1 to +28 | *[[Mycophenolate mofetil (CellCept)]] 1000 mg (route not specified) twice per day from day +1 to +28 | ||
− | <section end=" | + | '''One course''' |
− | + | </div> | |
+ | <section end="bfe435" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24827808/ PubMed] [https://clinicaltrials.gov/study/NCT00785330 NCT00785330] | |
− | |||
− | #'''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https:// | ||
− | |||
==Fludarabine & TBI for haploidentical transplant== | ==Fludarabine & TBI for haploidentical transplant== | ||
Flu/TBI: <u>'''Flu'''</u>darabine and '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | Flu/TBI: <u>'''Flu'''</u>darabine and '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen=== | ===Regimen=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/j.bbmt.2015.03.003 Soloman et al. 2014] | |[https://doi.org/10.1016/j.bbmt.2015.03.003 Soloman et al. 2014] | ||
+ | |2012-04 to 2014-05 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup>/day IV on days -7 to -5 (3 consecutive days) | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup>/day IV on days -7 to -5 (3 consecutive days) | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation]] 150 cGy twice per day on days -4 to -1 (total dose: 1200 cGy) | |
− | *[[External_beam_radiotherapy|Total body irradiation]] | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion | ||
*[[Mycophenolate mofetil (CellCept)]] 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present | *[[Mycophenolate mofetil (CellCept)]] 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present | ||
*[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180 | *[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180 | ||
+ | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. Epub 2015 Mar 19. [https://doi.org/10.1016/j.bbmt.2015.03.003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25797174/ PubMed] | + | #Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. Epub 2015 Mar 19. [https://doi.org/10.1016/j.bbmt.2015.03.003 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25797174/ PubMed] |
==BEAM {{#subobject:bda306|Regimen=1}}== | ==BEAM {{#subobject:bda306|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BEAM: '''<u>B</u>'''CNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | BEAM: '''<u>B</u>'''CNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen {{#subobject:a8d4a|Variant=1}}=== | + | ===Regimen variant #1 {{#subobject:a8d4a|Variant=1}}=== |
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1093/oxfordjournals.annonc.a010369 Przepiorka et al. 1999] | |[https://doi.org/10.1093/oxfordjournals.annonc.a010369 Przepiorka et al. 1999] | ||
− | | | + | |Not reported |
− | |||
− | |||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin="a8d4a" /> | <section begin="a8d4a" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6 | ||
*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV twice per day on days -5 to -2 | *[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV twice per day on days -5 to -2 | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV twice per day on days -5 to -2 | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV twice per day on days -5 to -2 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
*[[Tacrolimus (Prograf)]] | *[[Tacrolimus (Prograf)]] | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
− | ==== | + | ====Supportive therapy==== |
*"Prophylactic antibiotics" | *"Prophylactic antibiotics" | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +7 and continued until engraftment | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +7 and continued until engraftment | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="a8d4a" /> | <section end="a8d4a" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, attenuated {{#subobject:a8d4a3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3109/10428194.2013.838233 Sobol et al. 2013] | ||
+ | |2000-05 to 2012-04 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="a8d4a3" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -6 | ||
+ | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days -5 to -2 | ||
+ | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days -5 to -2 | ||
+ | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Tacrolimus (Prograf)]] | ||
+ | *[[Methotrexate (MTX)]] | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="a8d4a3" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. [https://doi.org/10.1093/oxfordjournals.annonc.a010369 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10416001/ PubMed] | |
− | #Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. [https://doi.org/10.1093/oxfordjournals.annonc.a010369 link to original article] ''' | + | #Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. [https://doi.org/10.3109/10428194.2013.838233 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23987822/ PubMed] |
− | #Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. [https:// | ||
==BFR {{#subobject:c2659b|Regimen=1}}== | ==BFR {{#subobject:c2659b|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BFR: '''<u>B</u>'''endamustine, '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab | BFR: '''<u>B</u>'''endamustine, '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:41fd04|Variant=1}}=== | ===Regimen {{#subobject:41fd04|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ Khouri et al. 2014 (MDACC 2008-0246)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ Khouri et al. 2014 (MDACC 2008-0246)] | ||
+ | |2009-04 to 2013-02 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin="41fd04" /> | <section begin="41fd04" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Bendamustine]] 130 mg/m<sup>2</sup> IV once per day on days -5 to -3 | *[[Bendamustine]] 130 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days -5 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days -5 to -3 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -13, -6, +1, +8 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -13, -6, +1, +8 | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | |||
*See article for GVHD prophylaxis information | *See article for GVHD prophylaxis information | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="41fd04" /> | <section end="41fd04" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''MDACC 2008-0246:''' Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. [https://doi.org/10.1182/blood-2014-07-587519 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25145344/ PubMed] [https://clinicaltrials.gov/study/NCT00880815 NCT00880815] | |
− | #'''MDACC 2008-0246:''' Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. [ | ||
=Reduced-intensity conditioning (RIC), all lines of therapy= | =Reduced-intensity conditioning (RIC), all lines of therapy= | ||
− | |||
==Busulfan & Fludarabine {{#subobject:3fe0f0|Regimen=1}}== | ==Busulfan & Fludarabine {{#subobject:3fe0f0|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | BuFlu: '''<u>Bu</u>'''sulfan & '''<u>Flu</u>'''darabine |
+ | <br>Flu/Bu: '''<u>Flu</u>'''darabine & '''<u>Bu</u>'''sulfan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 90/6.4 {{#subobject:a7ehw4|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00329-x de Masson et al. 2023 (CUTALLO)] | ||
+ | |2016-06-01 to 2022-03-03 | ||
+ | | style="background-color:#1a9851" |Propensity score analysis (E-esc) | ||
+ | |No transplant | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9 vs 3 mo<br>(HR 0.38, 95% CI 0.21-0.69) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | '''Diseases Studied: [[Cutaneous T-cell lymphoma]]''' | |
− | <br> | + | <section begin="a7ehw4" /> |
− | ===Regimen {{#subobject:a7e574|Variant=1}}=== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day for 3 days (days not specified) | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg/day IV for 2 days (days not specified) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Cyclosporine]] started on day -1, tapered on day +90 if no GVHD | ||
+ | *[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IV once on day +1, then 10 mg/m<sup>2</sup> IV once per day on days +3, +6, +11 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="a7ehw4" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 125/4 {{#subobject:e2d51e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1182/blood-2005-09-3869 Garban et al. 2006 (IFM99-03)] | ||
+ | |2000-04 to 2004-09 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |} | ||
+ | ''This regimen was meant for patients who had an HLA-identical sibling donor, and was evaluated in multiple myeloma patients.'' | ||
+ | <section begin="e2d51e" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup>/day (route not specified) for 5 days (days not specified) | ||
+ | *[[Busulfan (Myleran)]] 2 mg/kg PO once per day for 2 days (days not specified) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)|ATG, rabbit (Imtix)]] 2.5 mg/kg IV over 12 hours once per day on days -5 to -1 | ||
+ | *[[Cyclosporine]] 3 mg/kg/day (route not specified), starting on day -1 | ||
+ | *[[Methotrexate (MTX)]] 10 mg/m<sup>2</sup> (route not specified) once per day on days +1, +3, +6 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Cyclosporine doses adjusted to "serum levels", tapered on day +60 to off by day +100 (if no GVHD) | ||
+ | </div> | ||
+ | <section end="e2d51e" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Regimen variant #3, 150/6.4 {{#subobject:a7e574|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ Devine et al. 2015 (CALGB 100103)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ Devine et al. 2015 (CALGB 100103)] | ||
|2004-2011 | |2004-2011 | ||
− | | style="background-color:# | + | | style="background-color:#91cf61" |Phase 2 |
− | |||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S2352-3026(19)30157-7 Beelen et al. 2019 (MC-FludT.14/L)] |
|2013-2016 | |2013-2016 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Fludarabine_. | + | |[[#Fludarabine_.26_Treosulfan_888|Fludarabine & Treosulfan]] |
| style="background-color:#eeee01" |Non-inferior EFS24 | | style="background-color:#eeee01" |Non-inferior EFS24 | ||
− | |||
|- | |- | ||
|} | |} | ||
− | ''This regimen is meant for related donors; | + | ''This regimen is meant for related donors; in CALGB 100103, 8 patients received this regimen before the addition of ATG (rabbit) after 2006.'' |
<section begin="a7e574" /> | <section begin="a7e574" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days -7 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days -7 to -3 | ||
**MC-FludT.14/L gave the doses on days -6 to -2 | **MC-FludT.14/L gave the doses on days -6 to -2 | ||
*[[Busulfan (Myleran)]] 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg) | *[[Busulfan (Myleran)]] 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg) | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | + | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)|ATG (Rabbit)]] 2.5 mg/kg IV over 6 hours once per day on days -4 to -2 | |
*[[Tacrolimus (Prograf)]] with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD) | *[[Tacrolimus (Prograf)]] with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD) | ||
*[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | *[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="a7e574" /> | <section end="a7e574" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 150/360 {{#subobject:335733|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/cncr.29087 Mohty et al. 2014 (ITT 08-01)] | ||
+ | |2009-2011 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="335733" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup>/day (route not specified) on days -6 to -2 | ||
+ | *[[Busulfan (Myleran)]] 130 mg/m<sup>2</sup> IV over 3 hours once per day on days -5 to -3 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[:Category:Antithymocyte globulin|Antithymocyte globulin (ATG)]] (source not specified) 2.5 mg/kg/day IV on days -2 & -1 | ||
+ | *As per [https://pubmed.ncbi.nlm.nih.gov/12931226 Mohty et al. 2003] | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="335733" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5, 180/8 {{#subobject:e2c4bf|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 40%; text-align:center;" | ||
+ | ! style="width: 25%" |Study | ||
+ | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1182/blood.V91.3.756 Slavin et al. 1998] | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2003.12.011 Schetelig et al. 2003] | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="e2c4bf" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -10 to -5 (6 consecutive days) | ||
+ | *[[Busulfan (Myleran)]] 4 mg/kg/day PO on days -6 to -5 (2 consecutive days) | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Antithymocyte globulin, rabbit ATG (Grafalon)|ATG-Fresenius]] 10 mg/kg IV once per day on days -4 to -1 (4 consecutive days) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="e2c4bf" /> | ||
+ | </div> | ||
+ | ===References=== | ||
+ | #Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63. [https://doi.org/10.1182/blood.V91.3.756 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9446633/ PubMed] | ||
+ | #Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J, Sayer HG, Kroger N, Hensel M, Scheffold C, Held TK, Hoffken K, Ho AD, Kienast J, Neubauer A, Zander AR, Fauser AA, Ehninger G, Siegert W; Cooperative German Transplant Study Group. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. 2003 Jul 15;21(14):2747-53. [https://doi.org/10.1200/jco.2003.12.011 link to original article] '''contains reference to protocol''' [https://pubmed.ncbi.nlm.nih.gov/12860954/ PubMed] | ||
+ | #'''IFM99-03:''' Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. [https://doi.org/10.1182/blood-2005-09-3869 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16397129/ PubMed] | ||
+ | ##'''Pooled update:''' Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. [https://doi.org/10.1182/blood-2008-07-168823 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18948589/ PubMed] | ||
+ | #'''ITT 08-01:''' Mohty M, Malard F, Blaise D, Milpied N, Furst S, Tabrizi R, Guillaume T, Vigouroux S, El-Cheikh J, Delaunay J, Le Gouill S, Moreau P, Labopin M, Chevallier P. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial. Cancer. 2015 Feb 15;121(4):562-9. Epub 2014 Oct 3. Erratum in: Cancer. 2015 Mar 1;121(5):800. [https://doi.org/10.1002/cncr.29087 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25283774/ PubMed] [https://clinicaltrials.gov/study/NCT00841724 NCT00841724] | ||
+ | #'''CALGB 100103:''' Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. [https://doi.org/10.1200/jco.2015.62.7273 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658453/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527780/ PubMed] [https://clinicaltrials.gov/study/NCT00070135 NCT00070135] | ||
+ | #'''MC-FludT.14/L:''' Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stölzel F, Schetelig J, Junghanß C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Micò MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socié G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e28-e39. Epub 2019 Oct 9. [https://doi.org/10.1016/S2352-3026(19)30157-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31606445/ PubMed] [https://clinicaltrials.gov/study/NCT00822393 NCT00822393] | ||
+ | #'''CUTALLO:''' de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. [https://doi.org/10.1016/s0140-6736(23)00329-x link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37105210/ PubMed] [https://clinicaltrials.gov/study/NCT02520908 NCT02520908] | ||
+ | ==Busulfan, Fludarabine, Ibritumomab tiuxetan {{#subobject:68bee2|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:822e5a|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 40%; text-align:center;" | ||
+ | ! style="width: 25%" |Study | ||
+ | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdu503 Bouabdallah et al. 2015 (ZEVALLO)] | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <section begin="822e5a" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2 | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg/day (route not specified) on days -5 & -4 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days -21 & -14 | ||
+ | ====Radioconjugate therapy==== | ||
+ | *[[Ibritumomab tiuxetan (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2.5 mg/kg IV once on day -1 | ||
+ | *[[Cyclosporine]] (dose not specified) until day +90 and tapered off by day +180 based on chimerism and GVHD | ||
+ | *[[Methotrexate (MTX)]] by the following donor-based criteria: | ||
+ | **Unrelated donors with HLA mismatch: 15 mg/m<sup>2</sup> (route not specified) once on day +1, then 10 mg/m<sup>2</sup> (route not specified) once per day on days +3 & +6 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="822e5a" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''ZEVALLO:''' Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. [https://doi.org/10.1093/annonc/mdu503 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25361987/ PubMed] [https://clinicaltrials.gov/study/NCT00607854 NCT00607854] | |
− | # | + | ==Busulfan, Fludarabine, Thiotepa {{#subobject:97rrf0|Regimen=1}}== |
− | #''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:iyrc24|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00329-x de Masson et al. 2023 (CUTALLO)] | ||
+ | |2016-06-01 to 2022-03-03 | ||
+ | | style="background-color:#1a9851" |Propensity score analysis (E-esc) | ||
+ | |No transplant | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9 vs 3 mo<br>(HR 0.38, 95% CI 0.21-0.69) | ||
+ | |- | ||
+ | |} | ||
+ | '''Diseases Studied: [[Cutaneous T-cell lymphoma]]''' | ||
+ | <section begin="iyrc24" /> | ||
+ | ''Note: this preparative regimen was intended for haploidentical HSCT.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fludarabine (Fludara)]] 50 mg/m<sup>2</sup> IV once per day for 3 days (days not specified) | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg/day IV for 3 days (days not specified) | ||
+ | *[[Thiotepa (Tepadina)]] 5 mg/kg IV once (day not specified) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days +3 & +5 | ||
+ | *[[Cyclosporine]] started on day -1, tapered on day +90 if no GVHD | ||
+ | *[[Mycophenolate mofetil (CellCept)]] 15 mg/kg PO three times per day until day +35 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="iyrc24" /> | ||
+ | </div> | ||
+ | ===References=== | ||
+ | #'''CUTALLO:''' de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. [https://doi.org/10.1016/s0140-6736(23)00329-x link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37105210/ PubMed] [https://clinicaltrials.gov/study/NCT02520908 NCT02520908] | ||
==Clofarabine & Melphalan {{#subobject:08947a|Regimen=1}}== | ==Clofarabine & Melphalan {{#subobject:08947a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a408ed|Variant=1}}=== | ===Regimen {{#subobject:a408ed|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
Line 746: | Line 1,108: | ||
|} | |} | ||
''Limited details are available in the abstract. Treatment is meant to be given during aplasia.'' | ''Limited details are available in the abstract. Treatment is meant to be given during aplasia.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Acute_myeloid_leukemia#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine]] salvage | |
− | *[[Acute_myeloid_leukemia#Clofarabine_.26_Cytarabine|Clofarabine & Cytarabine | + | </div> |
<section begin="a408ed" /> | <section begin="a408ed" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Clofarabine (Clolar)]] 4 x 30 mg/m<sup>2</sup> IV | *[[Clofarabine (Clolar)]] 4 x 30 mg/m<sup>2</sup> IV | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="a408ed" /> | <section end="a408ed" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26283567/ PubMed] | |
− | #'''BRIDGE:''' Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. [https://doi.org/10.1038/leu.2015.226 link to original article] ''' | ||
− | |||
==Cyclophosphamide, Fludarabine, Thiotepa {{#subobject:ee93e3|Regimen=1}}== | ==Cyclophosphamide, Fludarabine, Thiotepa {{#subobject:ee93e3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:81245f|Variant=1}}=== | ===Regimen {{#subobject:81245f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V99.1.75 Corradini et al. 2002] |
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
− | |||
<section begin="81245f" /> | <section begin="81245f" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Cyclophosphamide (Cytoxan)]] 30 mg/kg IV once per day on days -4 & -3 | |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -4 & -3, given 4 hours after cyclophosphamide |
− | *[[Fludarabine (Fludara)]] | + | *[[Thiotepa (Thioplex)]] by the following age-based criteria: |
− | *[[Thiotepa (Thioplex)]] | + | **Younger than 45 years old: 7.5 mg/kg IV once every 12 hours on day -6 (total dose 15 mg/kg) |
+ | **45 to 60 years old: 5 mg/kg IV once every 12 hours on day -6 (total dose 10 mg/kg) | ||
+ | **Older than 60 years old: 2.5 mg/kg IV once every 12 hours on day -6 (total dose 5 mg/kg) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="81245f" /> | <section end="81245f" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
+ | #Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002 Jan 1;99(1):75-82. [https://doi.org/10.1182/blood.V99.1.75 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11756155/ PubMed] | ||
− | + | ==Cyclophosphamide & Fludarabine (FC) {{#subobject:1a1ed9|Regimen=1}}== | |
− | |||
− | ==FC {{#subobject:1a1ed9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FC: '''<u>F</u>'''ludarabine & '''<u>C</u>'''yclophosphamide | FC: '''<u>F</u>'''ludarabine & '''<u>C</u>'''yclophosphamide | ||
− | ===Regimen variant #1, | + | <br>FluCy: '''<u>Flu</u>'''darabine & '''<u>Cy</u>'''clophosphamide |
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 150/2500 {{#subobject:886e40|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 40%; text-align:center;" | ||
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2010-03-275420 Dreger et al. 2010 (GCLLSG CLL3X)] |
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | |||
<section begin="886e40" /> | <section begin="886e40" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) | |
− | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2 | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) |
− | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days -6 to -2 | + | ====GVHD prophylaxis==== |
+ | *[[Antithymocyte globulin, rabbit ATG (Grafalon)|ATG-Fresenius]] by the following donor-based criteria: | ||
+ | **Unrelated donors: 10 mg/kg/day IV on days -4 to -1 (4 consecutive days) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="886e40" /> | <section end="886e40" /> | ||
− | ===Regimen variant #2, | + | </div><br> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | ! style="width: | + | ===Regimen variant #2, 125/120 {{#subobject:9ce8f1|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM200009143431101 Childs et al. 2000 (NIH 97-H-0196)] |
− | | style="background-color:#ffffbe" |Non-randomized, | + | |1998-02 to 1999-08 |
+ | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
<section begin="9ce8f1" /> | <section begin="9ce8f1" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days -5 to -1 | *[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days -5 to -1 | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -7 & -6 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -7 & -6 | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="9ce8f1" /> | <section end="9ce8f1" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''NIH 97-H-0196:''' Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Clave E, Epperson D, Mayo V, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. [https://doi.org/10.1056/NEJM200009143431101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10984562/ PubMed] | |
− | #Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. [https:// | + | #'''GCLLSG CLL3X:''' Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. Epub 2010 Jul 1. [https://doi.org/10.1182/blood-2010-03-275420 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20595516/ PubMed] [https://clinicaltrials.gov/study/NCT00281983 NCT00281983] |
− | + | ##'''Update:''' Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. Epub 2013 Feb 22. [https://doi.org/10.1182/blood-2012-11-469627 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23435461/ PubMed] | |
− | #'''GCLLSG CLL3X:''' Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. Epub 2010 Jul 1. [ | + | ##'''Update:''' Krämer I, Stilgenbauer S, Dietrich S, Böttcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Döhner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. Epub 2017 Jul 17. [https://doi.org/10.1182/blood-2017-04-775841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28716861/ PubMed] |
− | ##'''Update:''' Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. Epub 2013 Feb 22. [ | ||
− | ##'''Update:''' Krämer I, Stilgenbauer S, Dietrich S, Böttcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Döhner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. Epub 2017 Jul 17. [ | ||
==FBM {{#subobject:1hg71a|Regimen=1}}== | ==FBM {{#subobject:1hg71a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FBM: '''<u>F</u>'''ludarabine, '''<u>B</u>'''CNU (Carmustine), '''<u>M</u>'''elphalan | FBM: '''<u>F</u>'''ludarabine, '''<u>B</u>'''CNU (Carmustine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1 {{#subobject:4f0684|Variant=1}}=== | ===Regimen variant #1 {{#subobject:4f0684|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 845: | Line 1,225: | ||
|} | |} | ||
''Note: this variant is intended for patients younger than 55 years of age.'' | ''Note: this variant is intended for patients younger than 55 years of age.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -9 to -5 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -9 to -5 | ||
*[[Carmustine (BCNU)]] 200 mg/m<sup>2</sup> IV once per day on days -7 & -6 | *[[Carmustine (BCNU)]] 200 mg/m<sup>2</sup> IV once per day on days -7 & -6 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -4 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -4 | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:4f0684|Variant=1}}=== | ===Regimen variant #2 {{#subobject:4f0684|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 60%; text-align:center;" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 862: | Line 1,247: | ||
|} | |} | ||
''Note: this variant is intended for patients 55 years of age and older.'' | ''Note: this variant is intended for patients 55 years of age and older.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -9 to -5 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -9 to -5 | ||
*[[Carmustine (BCNU)]] 150 mg/m<sup>2</sup> IV once per day on days -7 & -6 | *[[Carmustine (BCNU)]] 150 mg/m<sup>2</sup> IV once per day on days -7 & -6 | ||
*[[Melphalan (Alkeran)]] 110 mg/m<sup>2</sup> IV once on day -4 | *[[Melphalan (Alkeran)]] 110 mg/m<sup>2</sup> IV once on day -4 | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008 Jul 15;112(2):415-25. Epub 2008 May 1. [https://doi.org/10.1182/blood-2007-08-104745 link to original article] ''' | + | #Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008 Jul 15;112(2):415-25. Epub 2008 May 1. [https://doi.org/10.1182/blood-2007-08-104745 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18451310/ PubMed] |
− | |||
==FCR {{#subobject:18605a|Regimen=1}}== | ==FCR {{#subobject:18605a|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FCR: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab | FCR: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:4f0684|Variant=1}}=== | ===Regimen {{#subobject:4f0684|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V98.13.3595 Khouri et al. 2001 (MDACC ID01-233)] |
+ | |1997-2000 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin="4f0684" /> | <section begin="4f0684" /> | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
''Details are best described in the 2008 update.'' | ''Details are best described in the 2008 update.'' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once per day on days -5 to -3 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -13, then 1000 mg/m<sup>2</sup> IV once per day on days -6, +1, +8 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -13, then 1000 mg/m<sup>2</sup> IV once per day on days -6, +1, +8 | ||
− | + | ====Immunotherapy==== | |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | + | *[[Antithymocyte globulin, horse ATG (Atgam)]] by the following donor-based criteria: | |
− | *[[Antithymocyte globulin, horse ATG (Atgam)]] by the following criteria: | ||
**Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3 | **Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3 | ||
*[[Tacrolimus (Prograf)]] adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission | *[[Tacrolimus (Prograf)]] adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission | ||
− | *[[Methotrexate (MTX)]] by the following criteria: | + | *[[Methotrexate (MTX)]] by the following donor-based criteria: |
**Related donors: 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6 | **Related donors: 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6 | ||
**Unrelated donors: 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | **Unrelated donors: 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | ||
− | + | '''One course''' | |
+ | </div> | ||
<section end="4f0684" /> | <section end="4f0684" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [https://doi.org/10.1182/blood.V98.13.3595 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11739162/ PubMed] [https://clinicaltrials.gov/study/NCT00048737 NCT00048737] | |
− | #'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [ | + | ##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [https://doi.org/10.1182/blood-2008-01-136242 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18411419/ PubMed] |
− | ##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [ | + | ##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [https://doi.org/10.1182/blood-2012-03-417808 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22586182/ PubMed] |
− | ##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [ | ||
− | |||
==Fludarabine & TBI {{#subobject:53c6af|Regimen=1}}== | ==Fludarabine & TBI {{#subobject:53c6af|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:be3609|Variant=1}}=== | ===Regimen variant #1 {{#subobject:be3609|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 928: | Line 1,308: | ||
!style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | !style="width: 17%"|[[Levels_of_Evidence#Efficacy|Non-relapse mortality]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70349-2 Bornhäuser et al. 2012 (9005-2003)] |
|2004-2009 | |2004-2009 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
Line 937: | Line 1,317: | ||
|} | |} | ||
<section begin="be3609" /> | <section begin="be3609" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -3 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy fractions x 4 doses on days -3 & -2 (800 cGy total) | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy fractions x 4 doses on days -3 & -2 ( | + | ====Immunotherapy==== |
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="be3609" /> | <section end="be3609" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}=== | ===Regimen variant #2, low-dose TBI{{#subobject:7fa6ce|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 965: | Line 1,349: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2003-02-0482 Maris et al. 2003] |
|2000-2001 | |2000-2001 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
Line 973: | Line 1,357: | ||
|[https://doi.org/10.1200/jco.2010.32.7312 Björkstrand et al. 2011 (EBMT-NMAM2000)] | |[https://doi.org/10.1200/jco.2010.32.7312 Björkstrand et al. 2011 (EBMT-NMAM2000)] | ||
|2001-2005 | |2001-2005 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 981: | Line 1,365: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Low-dose_TBI|Low-dose TBI]] | |[[#Low-dose_TBI|Low-dose TBI]] | ||
− | | style="background-color:#d9ef8b" |Might have superior | + | | style="background-color:#d9ef8b" |Might have superior OS36 (primary endpoint) |
|- | |- | ||
|} | |} | ||
''Details are best described in Maris et al. 2003.'' | ''Details are best described in Maris et al. 2003.'' | ||
<section begin="7fa6ce" /> | <section begin="7fa6ce" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -4 to -2 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -4 to -2 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy at a rate of 7 cGy/min on day 0 | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | |||
*[[Cyclosporine]] 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD) | *[[Cyclosporine]] 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD) | ||
*[[Mycophenolate mofetil (CellCept)]] 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD) | *[[Mycophenolate mofetil (CellCept)]] 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD) | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="7fa6ce" /> | <section end="7fa6ce" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D, Petersdorf E, McSweeney P, Pulsipher M, Woolfrey A, Chauncey T, Agura E, Heimfeld S, Slattery J, Hegenbart U, Anasetti C, Blume K, Storb R. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003 Sep 15;102(6):2021-30. Epub 2003 Jun 5. [https://doi.org/10.1182/blood-2003-02-0482 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12791654/ PubMed] | |
− | #Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D, Petersdorf E, McSweeney P, Pulsipher M, Woolfrey A, Chauncey T, Agura E, Heimfeld S, Slattery J, Hegenbart U, Anasetti C, Blume K, Storb R. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003 Sep 15;102(6):2021-30. Epub 2003 Jun 5. [ | + | #Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 1;23(16):3819-29. Epub 2005 Apr 4. [https://doi.org/10.1200/jco.2005.04.569 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15809448/ PubMed] |
− | + | ##'''Update:''' Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. 2008 Oct 20;26(30):4912-20. Epub 2008 Sep 15. [https://doi.org/10.1200/jco.2007.15.4757 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652085/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18794548/ PubMed] | |
− | + | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626/ PubMed] | |
− | ##'''Update:''' Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. 2008 Oct 20;26(30):4912-20. Epub 2008 Sep 15. [https://doi.org/10.1200/jco.2007.15.4757 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652085/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18794548 PubMed] | + | #'''EBMT-NMAM2000:''' Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. [https://doi.org/10.1200/jco.2010.32.7312 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21730266/ PubMed] |
− | + | ##'''Update:''' Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. [https://doi.org/10.1182/blood-2012-11-469452 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23482933/ PubMed] | |
− | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] ''' | + | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https://doi.org/10.1016/S1470-2045(12)70349-2 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22959335/ PubMed] [https://clinicaltrials.gov/study/NCT00150878 NCT00150878] |
− | #'''EBMT-NMAM2000:''' Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. [https://doi.org/10.1200/jco.2010.32.7312 link to original article] ''' | + | #'''FHCRC 1813.00:''' Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hübel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. Epub 2013 Jun 11. [https://doi.org/10.1016/j.bbmt.2013.06.002 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755028/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23769990/ PubMed] [https://clinicaltrials.gov/study/NCT00075478 NCT00075478] |
− | ##'''Update:''' Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. [ | ||
− | #'''9005-2003:''' Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. [https:// | ||
− | #'''FHCRC 1813.00:''' Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hübel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. Epub 2013 Jun 11. [https:// | ||
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==Fludarabine, Cyclophosphamide, TBI for dUCB or haploidentical transplant {{#subobject:3a1faf|Regimen=1}}== | ==Fludarabine, Cyclophosphamide, TBI for dUCB or haploidentical transplant {{#subobject:3a1faf|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
dUCB: '''<u>d</u>'''ouble '''<u>U</u>'''mbilical '''<u>C</u>'''ord '''<u>B</u>'''lood | dUCB: '''<u>d</u>'''ouble '''<u>U</u>'''mbilical '''<u>C</u>'''ord '''<u>B</u>'''lood | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, dUCB transplantation {{#subobject:f5d1b1|Variant=1}}=== | ===Regimen variant #1, dUCB transplantation {{#subobject:f5d1b1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ Brunstein et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ Brunstein et al. 2011 (BMT CTN 0604)] |
+ | |2009-01 to 2010-03 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin="f5d1b1" /> | <section begin="f5d1b1" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) | *[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) | ||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once on day -6 | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once on day -6 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy once on day -1 | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
− | ====Supportive | + | ====Supportive therapy==== |
− | |||
*[[Mesna (Mesnex)]] (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection." | *[[Mesna (Mesnex)]] (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection." | ||
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +1, continued until ANC greater than or equal to 2000/ | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +1, continued until ANC greater than or equal to 2000/μL for 3 consecutive days |
− | |||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | + | *[[Mycophenolate mofetil (CellCept)]] by the following weight-based criteria: | |
− | *[[Mycophenolate mofetil (CellCept)]] 1000 mg (route not specified) every 8 hours | + | **More than 50 kg: 1000 mg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later" |
− | ** | + | **Less than 50 kg: 15 mg/kg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later" |
*[[Cyclosporine]] (route not specified) with a goal trough of 200 to 400 ng/mL (starting date not specified) until day +100. Patients without GVHD had their dose tapered by 10% each week starting on day +101, with discontinuation of cyclosporine A around day +180 to +200. | *[[Cyclosporine]] (route not specified) with a goal trough of 200 to 400 ng/mL (starting date not specified) until day +100. Patients without GVHD had their dose tapered by 10% each week starting on day +101, with discontinuation of cyclosporine A around day +180 to +200. | ||
*[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL could be substituted for cyclosporine. | *[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL could be substituted for cyclosporine. | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="f5d1b1" /> | <section end="f5d1b1" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, Haploidentical {{#subobject:61264d|Variant=1}}=== | ===Regimen variant #2, Haploidentical {{#subobject:61264d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ Brunstein et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ Brunstein et al. 2011 (BMT CTN 0603)] |
+ | |2009-01 to 2010-03 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin="61264d" /> | <section begin="61264d" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -6 to -2 (5 consecutive days) | ||
*[[Cyclophosphamide (Cytoxan)]] 14.5 mg/kg IV once per day on days -6 and -5 (2 consecutive days) | *[[Cyclophosphamide (Cytoxan)]] 14.5 mg/kg IV once per day on days -6 and -5 (2 consecutive days) | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy once on day -1 | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
− | ====Supportive | + | ====Supportive therapy==== |
− | |||
*[[Mesna (Mesnex)]] (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection." | *[[Mesna (Mesnex)]] (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection." | ||
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +5, continued until ANC greater than or equal to 1000/ | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +5, continued until ANC greater than or equal to 1000/μL for 3 consecutive days |
− | |||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion | ||
*[[Mycophenolate mofetil (CellCept)]] 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present | *[[Mycophenolate mofetil (CellCept)]] 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present | ||
*[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180 | *[[Tacrolimus (Prograf)]] (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="61264d" /> | <section end="61264d" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''BMT CTN 0603:''' Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; BMT CTN. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. Epub 2011 Apr 28. [https://doi.org/10.1182/blood-2011-03-344853 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21527516/ PubMed] [https://clinicaltrials.gov/study/NCT00849147 NCT00849147] | |
− | #Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; BMT CTN. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. [ | + | #'''BMT CTN 0604:''' Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; BMT CTN. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. Epub 2011 Apr 28. [https://doi.org/10.1182/blood-2011-03-344853 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138683/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21527516/ PubMed] [https://clinicaltrials.gov/study/NCT00864227 NCT00864227] |
+ | #'''BMT CTN 0501:''' Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, Walters M, Horowitz MM, Kurtzberg J; Blood and Marrow Transplant Clinical Trials Network. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014 Oct 30;371(18):1685-94. [https://doi.org/10.1056/nejmoa1405584 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4257059/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25354103/ PubMed] [https://clinicaltrials.gov/study/NCT00412360 NCT00412360] | ||
+ | #'''BMT CTN 1101:''' Fuchs EJ, O'Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, Devine S, Horowitz MM, Horwitz ME, Karanes C, Leifer E, Magenau JM, McGuirk JP, Morris LE, Rezvani AR, Jones RJ, Brunstein CG. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021 Jan 21;137(3):420-428. [https://doi.org/10.1182/blood.2020007535 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7819761/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33475736/ PubMed] [https://clinicaltrials.gov/study/NCT01597778 NCT01597778] | ||
+ | ##'''QoL analysis:''' El Jurdi N, Martens MJ, Brunstein CG, O'Donnell P, Lee SJ, D'Souza A, Logan B, Hong S, Singh AK, Sandhu K, Shapiro RM, Horowitz MM, Hamilton BK. Health-Related Quality of Life in Double Umbilical Cord Blood versus Haploidentical Marrow Transplantation: A Quality of Life Analysis Report of BMT CTN 1101. Transplant Cell Ther. 2023 Jul;29(7):467.e1-467.e5. Epub 2023 Apr 22. [https://doi.org/10.1016/j.jtct.2023.04.009 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10330136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37088401/ PubMed] | ||
==Fludarabine & Melphalan {{#subobject:1e26e2|Regimen=1}}== | ==Fludarabine & Melphalan {{#subobject:1e26e2|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | Flu-Mel: '''<u>Flu</u>'''darabine & '''<u>Mel</u>'''phalan |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 90/140 {{#subobject:ojnvwc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00329-x de Masson et al. 2023 (CUTALLO)] | ||
+ | |2016-06-01 to 2022-03-03 | ||
+ | | style="background-color:#1a9851" |Propensity score analysis (E-esc) | ||
+ | |No transplant | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9 vs 3 mo<br>(HR 0.38, 95% CI 0.21-0.69) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | '''Diseases Studied: [[Cutaneous T-cell lymphoma]]''' | |
− | ===Regimen variant # | + | <section begin="ojnvwc" /> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | ! style="width: | + | ====Chemotherapy==== |
− | ! style="width: | + | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day for 3 days (days not specified) |
+ | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once (day not specified) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Allogeneic stem cells]] transfused on day 0 | ||
+ | ====GVHD prophylaxis==== | ||
+ | *[[Cyclosporine]] started on day -1, tapered on day +90 if no GVHD | ||
+ | *[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IV once on day +1, then 10 mg/m<sup>2</sup> IV once per day on days +3, +6, +11 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end="ojnvwc" /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 132/140 {{#subobject:efd75c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238917/ Anderlini et al. 2008] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238917/ Anderlini et al. 2008] | ||
+ | |2001-2005 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | '''Diseases Studied: [[Classical Hodgkin lymphoma]]''' | ||
<section begin="efd75c" /> | <section begin="efd75c" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 33 mg/m<sup>2</sup> IV once per day on days -5 to -2 | *[[Fludarabine (Fludara)]] 33 mg/m<sup>2</sup> IV once per day on days -5 to -2 | ||
*[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -3 & -2 | *[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -3 & -2 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | |||
− | * | ||
− | |||
− | |||
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | + | *[[:Category:Antithymocyte globulin|ATG]] (type not specified) by the following donor-based criteria: | |
+ | **Matched unrelated donor: 2 mg/kg IV once per day on days -4 to -2 | ||
*[[Tacrolimus (Prograf)]] IV starting on day -2, dosed to achieve serum levels 4 to 12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given). | *[[Tacrolimus (Prograf)]] IV starting on day -2, dosed to achieve serum levels 4 to 12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given). | ||
*[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients) | *[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients) | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="efd75c" /> | <section end="efd75c" /> | ||
− | ===Regimen variant # | + | </div><br> |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | ! style="width: | + | ===Regimen variant #3, 150/140 {{#subobject:3239ec|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.bbmt.2005.09.009 Alvarez et al. 2006] |
+ | |1999-06 to 2004-01 | ||
| style="background-color:#91cf61" |Prospective | | style="background-color:#91cf61" |Prospective | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269494/ Sureda et al. 2011 (HDR-ALLO)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269494/ Sureda et al. 2011 (HDR-ALLO)] | ||
+ | |Not reported | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | '''Diseases Studied: [[Classical Hodgkin lymphoma]]'''<br> | ||
+ | ''Note: Alvarez et al. 2006 began CsA on day -1 and did not give day +11 MTX.'' | ||
<section begin="3239ec" /> | <section begin="3239ec" /> | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -8 to -4 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -8 to -4 | ||
*[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -3 & -2 | *[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -3 & -2 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis==== | |
− | *Recipients of stem cells from matched unrelated donors | + | *Recipients of stem cells from matched unrelated donors received: |
**Alvarez et al. 2006: [[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2.5 mg/kg IV once per day on days -4 to -2 | **Alvarez et al. 2006: [[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 2.5 mg/kg IV once per day on days -4 to -2 | ||
**HDR-ALLO: [[:Category:Antithymocyte globulin|ATG]] (type not specified) 45 mg/kg IV once per day on days -4 to -2 | **HDR-ALLO: [[:Category:Antithymocyte globulin|ATG]] (type not specified) 45 mg/kg IV once per day on days -4 to -2 | ||
− | |||
− | |||
− | |||
*[[Cyclosporine]] starting on day -2 at 1.5 mg/kg IV twice per day | *[[Cyclosporine]] starting on day -2 at 1.5 mg/kg IV twice per day | ||
**''If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +150 (Alvarez et al. 2006) or +180 (HDR-ALLO).'' | **''If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +150 (Alvarez et al. 2006) or +180 (HDR-ALLO).'' | ||
*[[Methotrexate (MTX)]] 10 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | *[[Methotrexate (MTX)]] 10 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11 | ||
− | + | '''One course''' | |
− | + | </div> | |
− | |||
<section end="3239ec" /> | <section end="3239ec" /> | ||
− | + | </div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #4, 150/40, with alemtuzumab {{#subobject:149798|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | |||
− | |||
− | |||
− | |||
− | ===Regimen {{#subobject:149798|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | ||
− | ! style="width: | ||
− | ! style="width: | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s0140-6736(05)66659-7 Peggs et al. 2005] |
+ | |1997-10-3 to 2003-08-21 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
<section begin="149798" /> | <section begin="149798" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -7 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -7 to -3 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis==== | |
*[[Alemtuzumab (Campath)]] | *[[Alemtuzumab (Campath)]] | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="149798" /> | <section end="149798" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D, Craddock C, Pettengell R, Dogan A, Thomson KJ, Morris EC, Hale G, Waldmann H, Goldstone AH, Linch DC, Mackinnon S. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet. 2005 Jun 4-10;365(9475):1934-41. [https://doi.org/10.1016/s0140-6736(05)66659-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15936420/ PubMed] | |
− | #Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D, Craddock C, Pettengell R, Dogan A, Thomson KJ, Morris EC, Hale G, Waldmann H, Goldstone AH, Linch DC, Mackinnon S. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet. 2005 Jun 4-10;365(9475):1934-41. [https://www. | + | #Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed Hodgkin lymphoma: results of a Spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. [https://doi.org/10.1016/j.bbmt.2005.09.009 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16443515/ PubMed] |
− | + | #Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated MD Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. [https://doi.org/10.3324/haematol.11828 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238917/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18223284/ PubMed] | |
+ | #'''HDR-ALLO:''' Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N; GEL/TAMO. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma: results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. [https://doi.org/10.3324/haematol.2011.045757 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269494/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21993674/ PubMed] | ||
+ | #'''CUTALLO:''' de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. [https://doi.org/10.1016/s0140-6736(23)00329-x link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37105210/ PubMed] [https://clinicaltrials.gov/study/NCT02520908 NCT02520908] | ||
==Low-dose TBI {{#subobject:529ee7|Regimen=1}}== | ==Low-dose TBI {{#subobject:529ee7|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:174a8e|Variant=1}}=== | ===Regimen {{#subobject:174a8e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
! style="width: 25%" |Study | ! style="width: 25%" |Study | ||
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
Line 1,377: | Line 1,611: | ||
|} | |} | ||
<section begin="174a8e" /> | <section begin="174a8e" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 200 cGy at a rate of 0.07 to 0.2000 cGy/min on day 0 | |
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | ====Immunotherapy==== |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
====GVHD prophylaxis==== | ====GVHD prophylaxis==== | ||
− | |||
*One of the following (further details not specified): | *One of the following (further details not specified): | ||
**[[Cyclosporine]] | **[[Cyclosporine]] | ||
**[[Tacrolimus (Prograf)]] | **[[Tacrolimus (Prograf)]] | ||
*[[Mycophenolate mofetil (CellCept)]] | *[[Mycophenolate mofetil (CellCept)]] | ||
− | + | '''One course''' | |
− | + | </div> | |
− | |||
<section end="174a8e" /> | <section end="174a8e" /> | ||
− | + | </div> | |
===References=== | ===References=== | ||
− | + | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439626/ PubMed] | |
− | + | ==TLI {{#subobject:49eb63|Regimen=1}}== | |
− | #Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.27.1460 link to original article] ''' | + | TLI: '''<u>T</u>'''otal '''<u>L</u>'''ymphocyte '''<u>I</u>'''rradiation |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ==TLI | ||
− | |||
− | |||
− | |||
− | |||
− | TLI | ||
===Regimen {{#subobject:dad2af|Variant=1}}=== | ===Regimen {{#subobject:dad2af|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa050642 Lowsky et al. 2005] |
+ | |2001-12-28 to 2004-12-01 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721787/ Kohrt et al. 2009] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721787/ Kohrt et al. 2009 (BMT153)] |
+ | |2001-12-28 to 2007-09-06 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
− | ''Note: the schedule for TLI in | + | ''Note: the schedule for TLI in BMT153 is slightly different, although the manuscript states that the protocol from Lowsky et al. 2005 was followed. See paper for details.'' |
<section begin="dad2af" /> | <section begin="dad2af" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | |||
*[[External_beam_radiotherapy|TLI]] 800 cGy once per day on days -11 to -1 (10 fractions) | *[[External_beam_radiotherapy|TLI]] 800 cGy once per day on days -11 to -1 (10 fractions) | ||
− | + | ====GVHD prophylaxis==== | |
− | ==== | ||
− | |||
*[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 1.5 mg/kg IV once per day on days -11 to -7 | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] 1.5 mg/kg IV once per day on days -11 to -7 | ||
− | + | ====Immunotherapy==== | |
− | + | *[[Allogeneic stem cells]] transfused on day 0 | |
− | + | '''One course''' | |
+ | </div> | ||
<section end="dad2af" /> | <section end="dad2af" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. Erratum in: N Engl J Med. 2006 Feb 23;354(8):884. [https://doi.org/10.1056/NEJMoa050642 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16192477/ PubMed] | |
− | #Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. Erratum in: N Engl J Med. 2006 Feb 23;354(8):884. [https:// | + | #'''BMT153:''' Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. Epub 2009 May 7. [https://doi.org/10.1182/blood-2009-03-211441 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721787/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19423725/ PubMed] [https://clinicaltrials.gov/study/NCT00185640 NCT00185640] |
− | #Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. [ | ||
==(90)YFC {{#subobject:ed22a7|Regimen=1}}== | ==(90)YFC {{#subobject:ed22a7|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
(90)YFC: Ibritumomab tiuxetan, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide | (90)YFC: Ibritumomab tiuxetan, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:efc342|Variant=1}}=== | ===Regimen {{#subobject:efc342|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood.V98.13.3595 Khouri et al. 2001 (MDACC ID01-233)] |
− | | style="background-color:#91cf61" | | + | |1997-2000 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: this regimen is specifically addressed in the 2012 update.'' | ''Note: this regimen is specifically addressed in the 2012 update.'' | ||
<section begin="efc342" /> | <section begin="efc342" /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days -14 & -7 | *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days -14 & -7 | ||
Line 1,456: | Line 1,684: | ||
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Indium-111 5 mCi]] IV once on day -14 for dosimetry | *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Indium-111 5 mCi]] IV once on day -14 for dosimetry | ||
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV once on day -7 | *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV once on day -7 | ||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 | *[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once per day on days -5 to -3 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
− | + | ====Immunotherapy==== | |
− | ==== | + | *[[Allogeneic stem cells]] transfused on day 0 |
− | + | ====GVHD prophylaxis==== | |
− | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] by the following criteria: | + | *[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]] by the following donor-based criteria: |
**Matched unrelated or mismatched donors: 1 mg/kg IV once per day on days -2 & -1 | **Matched unrelated or mismatched donors: 1 mg/kg IV once per day on days -2 & -1 | ||
− | |||
− | |||
− | |||
*[[Tacrolimus (Prograf)]] | *[[Tacrolimus (Prograf)]] | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end="efc342" /> | <section end="efc342" /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | #'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [ | + | #'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [https://doi.org/10.1182/blood.V98.13.3595 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11739162/ PubMed] [https://clinicaltrials.gov/study/NCT00048737 NCT00048737] |
− | ##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [ | + | ##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [https://doi.org/10.1182/blood-2008-01-136242 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18411419/ PubMed] |
− | ##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14 | + | ##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [https://doi.org/10.1182/blood-2012-03-417808 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22586182/ PubMed] |
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[[Category:Allogeneic HSCT regimens]] | [[Category:Allogeneic HSCT regimens]] | ||
[[Category:Site-agnostic regimens]] | [[Category:Site-agnostic regimens]] |
Latest revision as of 17:13, 17 July 2024
Section editor | |
---|---|
Talal Hilal, MD Mayo Clinic Phoenix, AZ, USA |
Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all allogeneic hematopoietic stem cell transplant (HSCT) conditioning regimens. Unless otherwise specified, the day before HSCT is day -1, the day of HSCT is day 0, and the day after HSCT is day +1. As with the rest of the HemOnc.org website, the focus here is on regimens used in the treatment of hematologic or oncologic conditions; there are roles for allogeneic HSCT outside of hematology/oncology but these use cases are considered to be out of scope.
These links will take you to highly related pages:
- Cellular therapy conditioning regimens
- Graft versus host disease (GVHD)
- Hepatic veno-occlusive disease (VOD)
- We have moved How I Treat articles to a dedicated page.
23 regimens on this page
41 variants on this page
|
Myeloablative regimens, all lines of therapy
BuCyTBI
BuCyTBI: Busulfan, Cyclophosphamide, Total Body Irradiation
Regimen
Study | Evidence |
---|---|
Fefer et al. 1979 | Pilot, fewer than 20 pts |
Chemotherapy
- Busulfan (Myleran) 5 mg/kg IV once on day -6
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -5 & -4
Radiotherapy
- TBI 920 rads on day 0
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Fefer A, Cheever MA, Thomas ED, Boyd C, Ramberg R, Glucksberg H, Buckner CD, Storb R. Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin. N Engl J Med. 1979 Feb 15;300(7):333-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Busulfan & Cyclophosphamide
BuCy: Busulfan & Cyclophosphamide
Regimen variant #1, 3.2 x 4/120
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Kröger et al. 2017 (RICMAC) | 2004-2012 | Phase 3 (C) | Bu/Flu RIC allo HSCT | Might have inferior OS | |
Lee et al. 2013 (COSAH C-005) | 2005-2009 | Phase 3 (C) | Busulfan & Fludarabine | Seems to have superior OS (secondary endpoint) | |
Rambaldi et al. 2015 (GITMO-AMLR2) | 2008-2012 | Phase 3 (C) | Busulfan & Fludarabine | Seems to have inferior 1-year non-relapse mortality | |
Zhang et al. 2023 | 2016-01 to 2020-02 | Phase 3 (E-switch-ooc) | TBI-Cy | Non-inferior OS24 (primary endpoint) OS24: 76.6% vs 79.4% |
Similar NRM |
Xuan et al. 2023 | 2016-04-18 to 2019-09-30 | Phase 3 (C) | Busulfan, Cyclophosphamide, Decitabine, G-CSF | Inferior CIR24 |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg)
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine
- Methotrexate (MTX) "according to the discretion of the attending physician"
Supportive therapy
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL
One course
Regimen variant #2, 0.8 x 16/120
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Andersson et al. 2002 | 1996-06 to 1997-12 | Phase 2 | |||
Ling et al. 2023 | 2015-11-20 to 2019-09-30 | Phase 3 (C) | BuFlu | Seems to have inferior TRM12 |
Chemotherapy
- Busulfan (Myleran) 0.8 mg/kg IV four times per per day on days -7 to -4 (total dose: 12.8 mg/kg)
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2 (total dose: 120 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #3, 1 x 16/200
Study | Evidence |
---|---|
Santos et al. 1983 | Non-randomized |
Chemotherapy
- Busulfan (Myleran) 1 mg/kg IV every 6 hours on days 1 to 4 (total dose: 16 mg/kg)
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days 5 to 8 (total dose: 200 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on unspecified day
One course
References
- Santos GW, Tutschka PJ, Brookmeyer R, Saral R, Beschorner WE, Bias WB, Braine HG, Burns WH, Elfenbein GJ, Kaizer H, Mellits D, Sensenbrenner LL, Stuart RK, Yeager AM. Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med. 1983 Dec 1;309(22):1347-53. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Andersson BS, Kashyap A, Gian V, Wingard JR, Fernandez H, Cagnoni PJ, Jones RB, Tarantolo S, Hu WW, Blume KG, Forman SJ, Champlin RE. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study. Biol Blood Marrow Transplant. 2002;8(3):145-54. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- COSAH C-005: Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00774280
- GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957
- RICMAC: Kröger N, Iacobelli S, Franke GN, Platzbecker U, Uddin R, Hübel K, Scheid C, Weber T, Robin M, Stelljes M, Afanasyev B, Heim D, Deliliers GL, Onida F, Dreger P, Pini M, Guidi S, Volin L, Günther A, Bethge W, Poiré X, Kobbe G, van Os M, Brand R, de Witte T. Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial). J Clin Oncol. 2017 Jul 1;35(19):2157-2164. Epub 2017 May 2. link to original article PubMed NCT01203228
- Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02670252
- Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02744742
- Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02487069
Busulfan, Cyclophosphamide, Decitabine, G-CSF
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Xuan et al. 2023 | 2016-04-18 to 2019-09-30 | Phase 3 (E-esc) | BuCy | Superior CIR24 (primary endpoint) CIR24: 10.9% vs 24.8% (HR 0.39, 95% CI 0.19-0.79) |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4 (total dose: 12.8 mg/kg)
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2 (total dose: 120 mg/kg)
- Decitabine (Dacogen) 20 mg/m2 IV once per day on days -14 to -10
Growth factor therapy
- G-CSF 5 mcg/kg once per day on days -17 to -10
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. Epub 2023 Jan 23. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02744742
Busulfan & Fludarabine
BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ling et al. 2023 | 2015-11-20 to 2019-09-30 | Phase 3 (E-de-esc) | Busulfan & Cyclophosphamide | Seems to have superior TRMM12 (primary endpoint) |
Diseases Studied: Acute myeloid leukemia
Chemotherapy
- Busulfan (Myleran) 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -7 to -3
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Rambaldi et al. 2015 (GITMO-AMLR2) | 2008-2012 | Phase 3 (E-switch-ic) | Busulfan & Cyclophosphamide | Seems to have superior NRM12 (primary endpoint) |
Diseases Studied: Acute myeloid leukemia
Graft types studied: Bone Marrow, Mobilized Peripheral Blood Stem Cells
Chemotherapy
- Busulfan (Myleran) 0.8 mg/kg IV four times per day for 2 hour infusions on days -6 to -3
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -3
GVHD prophylaxis, pre-transplant
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Matched unrelated donors: 0.5 mg/kg IV once on day -3, then 2 mg/kg IV once on day -2, then 2.5 mg/kg IV once on day -1
- Mismatched donors: total ATG dose could be increased to 7.5 mg/kg
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis, post-transplant
One course
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersson et al. 2008 | 1997-2005 | Non-randomized | Suggested improved outcomes, but shorter follow up | |
Kanakry et al. 2014 (J0844) | 2009-2011 | Phase 2 | ||
Mielcarek et al. 2016 (FHCC 2541.00) | 2011-2013 | Phase 2 | - |
Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Chronic myeloid leukemia, Non-Hodgkin lymphoma
Graft types studied: Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells
Chemotherapy
- Busulfan (Myleran) 130 mg/m2 IV over 3 hours once per day on days -6 to -3
- Dosing targeted for optimal pharmacokinetics but different parameters each institution, please consult the original publication for optimal levels
- Fludarabine (Fludara) 40 mg/m2 IV over 60 minutes once per day on days -6 to -3, given first
GVHD prophylaxis, pre-transplant
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Unrelated or mismatched donors: 0.5 mg/kg IV once on day -3, then 1.5 mg/kg IV once on day -2, then 2 mg/kg IV once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis, post-transplant
#1 Tacrolimus & methotrexate based (Andersson et al.)
Supportive therapy
- All patients received Filgrastim (Neupogen) SC once per day from day +7 until achieving an absolute neutrophil count (ANC) ≥1.5 x 109/L for three days
- Phenytoin (Dilantin) prophylaxis used during and for one day after IV busulfan
#2 Post-Transplant Cy based (Kanakry et al. and FHCC 2541.00)
GVHD prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days +3 & +4 (used alone in Kanakry et al. when all patients received bone marrow grafts)
- ± Cyclosporine intravenous loading dose of CSP was given on day 5, followed by subsequent twice per day dosing adjusted to maintain whole blood trough at 120 to 360 ng/mL. In abscence of GVHD Cyclosporine was tapered from day +56 through day +126 (used in FHCC 2541.00 with PBSCT grafts)
Supportive therapy
- Mesna (Mesnex) given with cyclophosphamide
One course
Regimen variant #4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2013 (COSAH C-005) | 2005-2009 | Phase 3 (E-switch-ic) | Busulfan & Cyclophosphamide | Seems to have inferior OS (secondary endpoint) |
Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Chronic myeloid leukemia, Myelofibrosis
Graft types studied: Matched Related / Unrelated Donor Bone Marrow, Mobilized Peripheral Blood Stem Cells
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -7 to -4, given first on days overlapping with fludarabine (total dose: 12.8 mg/kg)
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2, given second on days overlapping with busulfan
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- "Cyclosporine
- Methotrexate (MTX) "according to the discretion of the attending physician"
Supportive therapy
- Filgrastim (Neupogen) 450 mcg SC once per day, starting on day +5 and continued until ANC greater than 3000/μL
One course
Regimen variant #5
Study | Dates of enrollment | Evidence |
---|---|---|
Russell et al. 2002 | 1999-2001 | Phase 2 |
Diseases Studied: Acute myeloid leukemia, Myelodysplastic syndrome, Chronic myeloid leukemia, Chronic lymphocytic leukemia, Non-Hodgkin lymphoma, Hypereosinophilic syndrome
Graft types studied: Matched Related / Unrelated Donor Bone Marrow or Mobilized Peripheral Blood Stem Cells
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg (ideal body weight) IV over 3 hours once per day on days -5 to -2
- Fludarabine (Fludara) 50 mg/m2 IV once per day on days -6 to -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 0.5 mg/kg IV once on day -2, then 2 mg/kg IV once per day on days -1 & 0 (total dose of 4.5 mg/kg)
- Cyclosporine IV or PO twice per day, with doses adjusted to maintain cyclosporine levels of 150 to 400 umol/L
- Methotrexate (MTX) 15 mg/m2 (route not specified) once on day 1, then 10 mg/m2 (route not specified) once per day on days +3, +6, +11
Supportive therapy
- Leucovorin (Folinic acid) 5 mg started 24 hours after each dose of methotrexate and continued every 6 hours until 12 hours before the next dose of methotrexate
- Phenytoin (Dilantin) "loading" PO/IV, dosed to maintain therapeutic levels of 40 to 80 umol/L on days -5 to -2
One course
References
- Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002;8(9):468-76. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004 Aug 1;104(3):857-64. Epub 2004 Apr 8. link to original article PubMed
- Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE. Once daily IV busulfan and fludarabine (IV Bu-Flu) compares favorably with IV busulfan and cyclophosphamide (IV BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant. 2008;14(6):672-84. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- COSAH C-005: Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee JH, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH. Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol. 2013 Feb 20;31(6):701-9. Epub 2012 Nov 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00774280
- J0844: Kanakry CG, O'Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, Mielcarek M, Champlin RE, Jones RJ, Thall PF, Andersson BS, Luznik L. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497-505. Epub 2014 Sep 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00809276
- FHCC 2541.00: Mielcarek M, Furlong T, O'Donnell PV, Storer BE, McCune JS, Storb R, Carpenter PA, Flowers ME, Appelbaum FR, Martin PJ. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502-8. Epub 2016 Jan 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01427881
- GITMO-AMLR2: Rambaldi A, Grassi A, Masciulli A, Boschini C, Micò MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scimè R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-36. Epub 2015 Sep 28. link to original article PubMed NCT01191957
- MDACC 2011-0628: Andersson BS, Thall PF, Ma J, Valdez BC, Bassett R Jr, Chen J, Ahmed S, Alousi A, Bashir Q, Ciurea S, Gulbis A, Cool R, Kawedia J, Hosing C, Kebriaei P, Kornblau S, Myers A, Oran B, Rezvani K, Shah N, Shpall E, Parmar S, Popat UR, Nieto Y, Champlin RE. A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation. Bone Marrow Transplant. 2022 Aug;57(8):1295-1303. Epub 2022 May 24. link to original article link to PMC article PubMed NCT01471444
- Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. Epub 2023 Jun 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02487069
Cyclophosphamide & TBI
Cy/TBI: Cyclophosphamide & Total Body Irradiation
TBI-CY: Total Body Irradiation & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Rudolph et al. 1973 | 1968-1970 | Non-randomized | |||
Fefer et al. 1982 | 1971-1980 | Non-randomized, fewer than 20 pts | |||
Thomas et al. 1979 | 1976-1977 | Non-randomized | |||
Blume et al. 1980 | 1976-1979 | Non-randomized, fewer than 20 pts | |||
Johnson et al. 1981 | 1976-1980 | Non-randomized | |||
Brochstein et al. 1987 | 1979-1985 | Non-randomized | |||
Goldman et al. 1986 | 1981-1984 | Non-randomized | |||
Kersey et al. 1987 | 1982-1985 | Quasi-randomized | Auto HSCT | Superior RFS | |
Hansen et al. 1998 | 1985-1994 | Non-randomized | |||
Sebban et al. 1994 (LALA 87) | 1986-1991 | Phase 3 (E-esc) | Chemotherapy or Auto HSCT | Did not meet co-primary endpoints of DFS/OS | |
Zittoun et al. 1995 | 1986-1993 | Phase 3 (E-esc) | Intensive chemotherapy | Superior DFS | |
Thomas et al. 2004 (LALA-94) | 1994-2002 | Non-randomized part of RCT | |||
Bornhäuser et al. 2012 (9005-2003) | 2004-2009 | Phase 3 (C) | Fludarabine & TBI | Did not meet primary endpoint of NRM | |
Zhang et al. 2023 | 2016-01 to 2020-02 | Phase 3 (C) | BuCy | Non-inferior OS24 | Similar NRM |
Details in most of the manuscripts are limited.
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation by the following study-specific criteria:
- Zhang et al. 2023: 450 cGy once per day on days -5 & -4 (900 cGy total)
- Other studies: 10 to 1200 cGy total
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Rudolph RH, Fefer A, Thomas ED, Buckner CD, Clift RA, Storb R. Isogeneic marrow grafts for hematologic malignancy in man. Arch Intern Med. 1973 Aug;132(2):279-85. link to original article PubMed
- Update: Fefer A, Einstein AB, Thomas ED, Buckner CD, Clift RA, Glucksberg H, Neiman PE, Storb R. Bone-marrow transplantation for hematologic neoplasia in 16 patients with identical twins. N Engl J Med. 1974 Jun 20;290(25):1389-93. link to original article PubMed
- Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman SJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980 May 8;302(19):1041-6. link to original article PubMed
- Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. link to original article PubMed
- Fefer A, Cheever MA, Greenberg PD, Appelbaum FR, Boyd CN, Buckner CD, Kaplan HG, Ramberg R, Sanders JE, Storb R, Thomas ED. Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins. N Engl J Med. 1982 Jan 14;306(2):63-8. link to original article PubMed
- Goldman JM, Apperley JF, Jones L, Marcus R, Goolden AW, Batchelor R, Hale G, Waldmann H, Reid CD, Hows J, Gordon-Smith E, Catovsky D, Galton DAG. Bone marrow transplantation for patients with chronic myeloid leukemia. N Engl J Med. 1986 Jan 23;314(4):202-7. PubMed
- Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. link to original article PubMed
- Brochstein JA, Kernan NA, Groshen S, Cirrincione C, Shank B, Emanuel D, Laver J, O'Reilly RJ. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med. 1987 Dec 24;317(26):1618-24. link to original article PubMed
- LALA 87: Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D, Dreyfus F, Fiere D; French Group of Therapy of Adult Acute Lymphoblastic Leukemia. Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. J Clin Oncol. 1994 Dec;12(12):2580-7. link to original article PubMed
- Update: Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C, Lepage E, Thomas X, Fière D. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation: a follow-up report of the French protocol LALA 87. Hematol Oncol Clin North Am. 2000 Dec;14(6):1353-66. link to original article PubMed
- Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML, Petti MC, Solbu G, Suciu S; EORTC; Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med. 1995 Jan 26;332(4):217-23. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA, Petersdorf EW, Radich J, Sanders JE, Storb RF, Sullivan KM, Anasetti C. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998 Apr 2;338(14):962-8. link to original article PubMed
- LALA-94: Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, Fiere D. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004 Oct 15;22(20):4075-86. Epub 2004 Sep 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002700
- Update: Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J; Swiss Group for Clinical Cancer Research. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006 Dec;20(12):2155-61. Epub 2006 Oct 12. link to original article PubMed
- 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00150878
- Retrospective: Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013 Dec 5;122(24):3863-70. Epub 2013 Sep 24. link to original article link to PMC article PubMed
- Zhang H, Fan Z, Huang F, Han L, Xu Y, Xu N, Deng L, Wang S, Lin D, Luo X, Zhang Q, Liu X, Li X, Liang X, Xie S, Qu H, Yu S, Zhou H, Shi P, Xuan L, Lin R, Liu H, Jin H, Sun J, Liu Q. Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial. J Clin Oncol. 2023 Jan 10;41(2):343-353. Epub 2022 Sep 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02670252
- SWOG S9920: NCT00005866
Etoposide & TBI
Regimen variant #1, weight-based etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Balduzzi et al. 2005 | 1995-2000 | Quasi-randomized | Chemotherapy | Seems to have superior DFS |
Peters et al. 2015 (ALL-SCT-BFM 2003) | 2003-2011 | Non-randomized |
This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CR1.
Chemotherapy
- Etoposide (Vepesid) 60 mg/kg (maximum dose of 3600 mg) IV once on day -3
Radiotherapy
- Total body irradiation (TBI) 200 cGy twice per day in 6 fractions on days -6 to -4 with lung shielding at 1000 cGy (total dose: 1200 cGy)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #2, BSA-based etoposide
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Peters et al. 2020 (FORUM) | 2013-2018 | Phase 3 (C) | 1a. Busulfan, Fludarabine, Thiotepa 1b. Fludarabine, Thiotepa, Treosulfan |
Superior OS (primary endpoint) |
This regimen was evaluated in the treatment of high-risk pediatric acute lymphoblastic leukemia in CMR.
Chemotherapy
- Etoposide (Vepesid) 1800 mg/m2 (maximum dose of 3600 mg) IV once on day -3
Radiotherapy
- Total body irradiation (TBI) 200 cGy twice per day in 6 fractions on days -6 to -4 with lung shielding at 1000 cGy (total dose: 1200 cGy)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #3, 1320 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) | 1993-2003 | Non-randomized part of phase 3 RCT |
Note: this is the same preparative regimen used for autologous transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.
Chemotherapy
- Etoposide (Vepesid) 60 mg/kg IV once on day -3
Radiotherapy
- Total body irradiation (TBI) 220 cGy twice per day in 6 fractions on days -6 to -4 (total dose: 1320 cGy)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- MRC UKALL XII/ECOG E2993: Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002514
- Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
- Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
- Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- ALL-SCT-BFM-2003: Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. link to original article PubMed NCT01423747
- FORUM: Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Güngör T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M, von Stackelberg A, Balduzzi A, Corbacioglu S, Bader P; IBFM Study Group; IntReALL Study Group; I-BFM SCT Study Group; EBMT Paediatric Diseases Working Party. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. Epub 2020 Dec 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01949129
Fludarabine, Busulfan, Cyclophosphamide
FluBuCy: Fludarabine, Busulfan, Cyclophosphamide
Regimen variant #1, oral
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2014 (DSHNHL R3) | 2004-06-16 to 2009-03-24 | Phase 2 |
This is described by the authors as a lymphoma-directed myeloablative conditioning regimen
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2/day IV on days -8 to -4
- Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
- Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
- Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28
One course
Regimen variant #2, intravenous
Study | Dates of enrollment | Evidence |
---|---|---|
Glass et al. 2014 (DSHNHL R3) | 2004-06-16 to 2009-03-24 | Phase 2 |
This is described by the authors as a lymphoma-directed myeloablative conditioning regimen
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2/day IV on days -8 to -4
- Busulfan (Myleran) 3.2 mg/kg/day IV on days -6 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg/day IV on days -3 and -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2 mg/kg IV from day -3 to -1 (unclear if this is a total dose or a daily dose)
- Option also to use ATG-Fresenius S at a higher dose of 10 mg/kg
- Tacrolimus (Prograf) 8 to 12 mcg/L (route/frequency not specified) starting on day -1, tapered from day +100 in absence of GVHD
- Mycophenolate mofetil (CellCept) 1000 mg (route not specified) twice per day from day +1 to +28
One course
References
- DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) dosing details in manuscript have been reviewed by our editors PubMed NCT00785330
Fludarabine & TBI for haploidentical transplant
Flu/TBI: Fludarabine and Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Soloman et al. 2014 | 2012-04 to 2014-05 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2/day IV on days -7 to -5 (3 consecutive days)
Radiotherapy
- Total body irradiation 150 cGy twice per day on days -4 to -1 (total dose: 1200 cGy)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion
- Mycophenolate mofetil (CellCept) 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present
- Tacrolimus (Prograf) (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180
One course
References
- Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. Epub 2015 Mar 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
BEAM
BEAM: BCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Przepiorka et al. 1999 | Not reported | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV twice per day on days -5 to -2
- Cytarabine (Ara-C) 200 mg/m2 IV twice per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
Supportive therapy
- "Prophylactic antibiotics"
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +7 and continued until engraftment
One course
Regimen variant #2, attenuated
Study | Dates of enrollment | Evidence |
---|---|---|
Sobol et al. 2013 | 2000-05 to 2012-04 | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 100 mg/m2 IV twice per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
One course
References
- Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed
BFR
BFR: Bendamustine, Fludarabine, Rituximab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Khouri et al. 2014 (MDACC 2008-0246) | 2009-04 to 2013-02 | Phase 2 |
Chemotherapy
- Bendamustine 130 mg/m2 IV once per day on days -5 to -3
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -5 to -3
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -13, -6, +1, +8
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- See article for GVHD prophylaxis information
One course
References
- MDACC 2008-0246: Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00880815
Reduced-intensity conditioning (RIC), all lines of therapy
Busulfan & Fludarabine
BuFlu: Busulfan & Fludarabine
Flu/Bu: Fludarabine & Busulfan
Regimen variant #1, 90/6.4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Masson et al. 2023 (CUTALLO) | 2016-06-01 to 2022-03-03 | Propensity score analysis (E-esc) | No transplant | Superior PFS (primary endpoint) Median PFS: 9 vs 3 mo (HR 0.38, 95% CI 0.21-0.69) |
Diseases Studied: Cutaneous T-cell lymphoma
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day for 3 days (days not specified)
- Busulfan (Myleran) 3.2 mg/kg/day IV for 2 days (days not specified)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine started on day -1, tapered on day +90 if no GVHD
- Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11
One course
Regimen variant #2, 125/4
Study | Dates of enrollment | Evidence |
---|---|---|
Garban et al. 2006 (IFM99-03) | 2000-04 to 2004-09 | Non-randomized |
This regimen was meant for patients who had an HLA-identical sibling donor, and was evaluated in multiple myeloma patients.
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2/day (route not specified) for 5 days (days not specified)
- Busulfan (Myleran) 2 mg/kg PO once per day for 2 days (days not specified)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- ATG, rabbit (Imtix) 2.5 mg/kg IV over 12 hours once per day on days -5 to -1
- Cyclosporine 3 mg/kg/day (route not specified), starting on day -1
- Methotrexate (MTX) 10 mg/m2 (route not specified) once per day on days +1, +3, +6
One course
Dose and schedule modifications
- Cyclosporine doses adjusted to "serum levels", tapered on day +60 to off by day +100 (if no GVHD)
Regimen variant #3, 150/6.4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Devine et al. 2015 (CALGB 100103) | 2004-2011 | Phase 2 | ||
Beelen et al. 2019 (MC-FludT.14/L) | 2013-2016 | Phase 3 (C) | Fludarabine & Treosulfan | Non-inferior EFS24 |
This regimen is meant for related donors; in CALGB 100103, 8 patients received this regimen before the addition of ATG (rabbit) after 2006.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV over 30 minutes once per day on days -7 to -3
- MC-FludT.14/L gave the doses on days -6 to -2
- Busulfan (Myleran) 0.8 mg/kg IV over 2 hours every 6 hours on days -4 & -3 (total dose: 6.4 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- ATG (Rabbit) 2.5 mg/kg IV over 6 hours once per day on days -4 to -2
- Tacrolimus (Prograf) with doses adjusted to maintain levels of 5 to 10 ng/mL, tapered on day +90 to off by day +180 (if no GVHD)
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6, +11
One course
Regimen variant #4, 150/360
Study | Dates of enrollment | Evidence |
---|---|---|
Mohty et al. 2014 (ITT 08-01) | 2009-2011 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2/day (route not specified) on days -6 to -2
- Busulfan (Myleran) 130 mg/m2 IV over 3 hours once per day on days -5 to -3
GVHD prophylaxis
- Antithymocyte globulin (ATG) (source not specified) 2.5 mg/kg/day IV on days -2 & -1
- As per Mohty et al. 2003
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #5, 180/8
Study | Evidence |
---|---|
Slavin et al. 1998 | Phase 2 |
Schetelig et al. 2003 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -10 to -5 (6 consecutive days)
- Busulfan (Myleran) 4 mg/kg/day PO on days -6 to -5 (2 consecutive days)
GVHD prophylaxis
- ATG-Fresenius 10 mg/kg IV once per day on days -4 to -1 (4 consecutive days)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Schetelig J, Thiede C, Bornhauser M, Schwerdtfeger R, Kiehl M, Beyer J, Sayer HG, Kroger N, Hensel M, Scheffold C, Held TK, Hoffken K, Ho AD, Kienast J, Neubauer A, Zander AR, Fauser AA, Ehninger G, Siegert W; Cooperative German Transplant Study Group. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. 2003 Jul 15;21(14):2747-53. link to original article contains reference to protocol PubMed
- IFM99-03: Garban F, Attal M, Michallet M, Hulin C, Bourhis JH, Yakoub-Agha I, Lamy T, Marit G, Maloisel F, Berthou C, Dib M, Caillot D, Deprijck B, Ketterer N, Harousseau JL, Sotto JJ, Moreau P. Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood. 2006 May 1;107(9):3474-80. Epub 2006 Jan 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pooled update: Moreau P, Garban F, Attal M, Michallet M, Marit G, Hulin C, Benboubker L, Doyen C, Mohty M, Yakoub-Agha I, Leyvraz S, Casassus P, Avet-Loiseau H, Garderet L, Mathiot C, Harousseau JL; IFM. Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood. 2008 Nov 1;112(9):3914-5. link to original article PubMed
- ITT 08-01: Mohty M, Malard F, Blaise D, Milpied N, Furst S, Tabrizi R, Guillaume T, Vigouroux S, El-Cheikh J, Delaunay J, Le Gouill S, Moreau P, Labopin M, Chevallier P. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial. Cancer. 2015 Feb 15;121(4):562-9. Epub 2014 Oct 3. Erratum in: Cancer. 2015 Mar 1;121(5):800. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00841724
- CALGB 100103: Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. Epub 2015 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00070135
- MC-FludT.14/L: Beelen DW, Trenschel R, Stelljes M, Groth C, Masszi T, Reményi P, Wagner-Drouet EM, Hauptrock B, Dreger P, Luft T, Bethge W, Vogel W, Ciceri F, Peccatori J, Stölzel F, Schetelig J, Junghanß C, Grosse-Thie C, Michallet M, Labussiere-Wallet H, Schaefer-Eckart K, Dressler S, Grigoleit GU, Mielke S, Scheid C, Holtick U, Patriarca F, Medeot M, Rambaldi A, Micò MC, Niederwieser D, Franke GN, Hilgendorf I, Winkelmann NR, Russo D, Socié G, Peffault de Latour R, Holler E, Wolff D, Glass B, Casper J, Wulf G, Menzel H, Basara N, Bieniaszewska M, Stuhler G, Verbeek M, Grass S, Iori AP, Finke J, Benedetti F, Pichlmeier U, Hemmelmann C, Tribanek M, Klein A, Mylius HA, Baumgart J, Dzierzak-Mietla M, Markiewicz M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e28-e39. Epub 2019 Oct 9. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00822393
- CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT02520908
Busulfan, Fludarabine, Ibritumomab tiuxetan
Regimen
Study | Evidence |
---|---|
Bouabdallah et al. 2015 (ZEVALLO) | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2
- Busulfan (Myleran) 3.2 mg/kg/day (route not specified) on days -5 & -4
Targeted therapy
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -21 & -14
Radioconjugate therapy
- Ibritumomab tiuxetan (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2.5 mg/kg IV once on day -1
- Cyclosporine (dose not specified) until day +90 and tapered off by day +180 based on chimerism and GVHD
- Methotrexate (MTX) by the following donor-based criteria:
- Unrelated donors with HLA mismatch: 15 mg/m2 (route not specified) once on day +1, then 10 mg/m2 (route not specified) once per day on days +3 & +6
One course
References
- ZEVALLO: Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00607854
Busulfan, Fludarabine, Thiotepa
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Masson et al. 2023 (CUTALLO) | 2016-06-01 to 2022-03-03 | Propensity score analysis (E-esc) | No transplant | Superior PFS (primary endpoint) Median PFS: 9 vs 3 mo (HR 0.38, 95% CI 0.21-0.69) |
Diseases Studied: Cutaneous T-cell lymphoma
Note: this preparative regimen was intended for haploidentical HSCT.Chemotherapy
- Fludarabine (Fludara) 50 mg/m2 IV once per day for 3 days (days not specified)
- Busulfan (Myleran) 3.2 mg/kg/day IV for 3 days (days not specified)
- Thiotepa (Tepadina) 5 mg/kg IV once (day not specified)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days +3 & +5
- Cyclosporine started on day -1, tapered on day +90 if no GVHD
- Mycophenolate mofetil (CellCept) 15 mg/kg PO three times per day until day +35
One course
References
- CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT02520908
Clofarabine & Melphalan
Regimen
Study | Evidence |
---|---|
Middeke et al. 2015 (BRIDGE) | Phase 2 |
Limited details are available in the abstract. Treatment is meant to be given during aplasia.
Preceding treatment
- Clofarabine & Cytarabine salvage
Chemotherapy
- Clofarabine (Clolar) 4 x 30 mg/m2 IV
- Melphalan (Alkeran) 140 mg/m2 IV
Immunotherapy
- Allogeneic stem cells transfused on unspecified day
One course
References
- BRIDGE: Middeke JM, Herbst R, Parmentier S, Bug G, Hänel M, Stuhler G, Schäfer-Eckart K, Rösler W, Klein S, Bethge W, Bitz U, Büttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stölzel F, Platzbecker U, Röllig C, Thiede C, Ehninger G, Bornhäuser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. Epub 2015 Aug 18. link to original article dosing details in abstract have been reviewed by our editors PubMed
Cyclophosphamide, Fludarabine, Thiotepa
Regimen
Study | Evidence |
---|---|
Corradini et al. 2002 | Non-randomized |
Chemotherapy
- Cyclophosphamide (Cytoxan) 30 mg/kg IV once per day on days -4 & -3
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -4 & -3, given 4 hours after cyclophosphamide
- Thiotepa (Thioplex) by the following age-based criteria:
- Younger than 45 years old: 7.5 mg/kg IV once every 12 hours on day -6 (total dose 15 mg/kg)
- 45 to 60 years old: 5 mg/kg IV once every 12 hours on day -6 (total dose 10 mg/kg)
- Older than 60 years old: 2.5 mg/kg IV once every 12 hours on day -6 (total dose 5 mg/kg)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Corradini P, Tarella C, Olivieri A, Gianni AM, Voena C, Zallio F, Ladetto M, Falda M, Lucesole M, Dodero A, Ciceri F, Benedetti F, Rambaldi A, Sajeva MR, Tresoldi M, Pileri A, Bordignon C, Bregni M. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002 Jan 1;99(1):75-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cyclophosphamide & Fludarabine (FC)
FC: Fludarabine & Cyclophosphamide
FluCy: Fludarabine & Cyclophosphamide
Regimen variant #1, 150/2500
Study | Evidence |
---|---|
Dreger et al. 2010 (GCLLSG CLL3X) | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
GVHD prophylaxis
- ATG-Fresenius by the following donor-based criteria:
- Unrelated donors: 10 mg/kg/day IV on days -4 to -1 (4 consecutive days)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #2, 125/120
Study | Dates of enrollment | Evidence |
---|---|---|
Childs et al. 2000 (NIH 97-H-0196) | 1998-02 to 1999-08 | Non-randomized, fewer than 20 pts |
Chemotherapy
- Fludarabine (Fludara) 25 mg/m2 IV once per day on days -5 to -1
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -7 & -6
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- NIH 97-H-0196: Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Clave E, Epperson D, Mayo V, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GCLLSG CLL3X: Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, Bunjes D, Cohen S, Schubert J, Hegenbart U, Beelen D, Zeis M, Stadler M, Hasenkamp J, Uharek L, Scheid C, Humpe A, Zenz T, Winkler D, Hallek M, Kneba M, Schmitz N, Stilgenbauer S; German CLL Study Group. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010 Oct 7;116(14):2438-47. Epub 2010 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00281983
- Update: Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S. TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial. Blood. 2013 Apr 18;121(16):3284-8. Epub 2013 Feb 22. link to original article PubMed
- Update: Krämer I, Stilgenbauer S, Dietrich S, Böttcher S, Zeis M, Stadler M, Bittenbring J, Uharek L, Scheid C, Hegenbart U, Ho A, Hallek M, Kneba M, Schmitz N, Döhner H, Dreger P. Allogeneic hematopoietic cell transplantation for high-risk CLL: 10-year follow-up of the GCLLSG CLL3X trial. Blood. 2017 Sep 21;130(12):1477-1480. Epub 2017 Jul 17. link to original article PubMed
FBM
FBM: Fludarabine, BCNU (Carmustine), Melphalan
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Marks et al. 2008 | 1998-2003 | Phase 2 |
Note: this variant is intended for patients younger than 55 years of age.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -9 to -5
- Carmustine (BCNU) 200 mg/m2 IV once per day on days -7 & -6
- Melphalan (Alkeran) 140 mg/m2 IV once on day -4
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Marks et al. 2008 | 1998-2003 | Phase 2 |
Note: this variant is intended for patients 55 years of age and older.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -9 to -5
- Carmustine (BCNU) 150 mg/m2 IV once per day on days -7 & -6
- Melphalan (Alkeran) 110 mg/m2 IV once on day -4
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008 Jul 15;112(2):415-25. Epub 2008 May 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
FCR
FCR: Fludarabine, Cyclophosphamide, Rituximab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Khouri et al. 2001 (MDACC ID01-233) | 1997-2000 | Phase 2 |
Details are best described in the 2008 update.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -5 to -3
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days -5 to -3
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day -13, then 1000 mg/m2 IV once per day on days -6, +1, +8
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, horse ATG (Atgam) by the following donor-based criteria:
- Matched unrelated donor: 15 mg/kg IV once per day on days -5 to -3
- Tacrolimus (Prograf) adjusted to level of 5 to 10 ng/mL for 6 months in patients in remission
- Methotrexate (MTX) by the following donor-based criteria:
- Related donors: 5 mg/m2 IV once per day on days +1, +3, +6
- Unrelated donors: 5 mg/m2 IV once per day on days +1, +3, +6, +11
One course
References
- MDACC ID01-233: Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. link to original article PubMed NCT00048737
- Update: Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Fludarabine & TBI
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Non-relapse mortality |
---|---|---|---|---|---|
Bornhäuser et al. 2012 (9005-2003) | 2004-2009 | Phase 3 (E-switch-ic) | Cyclophosphamide & TBI | Did not meet primary endpoint of NRM |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -3
Radiotherapy
- Total body irradiation (TBI) 200 cGy fractions x 4 doses on days -3 & -2 (800 cGy total)
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
Regimen variant #2, low-dose TBI
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sorror et al. 2005 | 1997-2003 | Phase 2 | ||
Gyukocza et al. 2010 | 1998-2008 | Non-randomized | ||
Maris et al. 2003 | 2000-2001 | Phase 2 | ||
Björkstrand et al. 2011 (EBMT-NMAM2000) | 2001-2005 | Non-randomized part of RCT | ||
Kornblit et al. 2013 (FHCRC 1813.00) | 2003-2011 | Phase 3 (E-esc) | Low-dose TBI | Might have superior OS36 (primary endpoint) |
Details are best described in Maris et al. 2003.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -4 to -2
Radiotherapy
- Total body irradiation (TBI) 200 cGy at a rate of 7 cGy/min on day 0
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine 6.25 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 100 over 80 days (if no GVHD)
- Mycophenolate mofetil (CellCept) 15 mg/kg PO twice per day starting 4 to 6 hours after transplant, tapered at day 40 over 56 days (if no GVHD)
One course
References
- Maris MB, Niederwieser D, Sandmaier BM, Storer B, Stuart M, Maloney D, Petersdorf E, McSweeney P, Pulsipher M, Woolfrey A, Chauncey T, Agura E, Heimfeld S, Slattery J, Hegenbart U, Anasetti C, Blume K, Storb R. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003 Sep 15;102(6):2021-30. Epub 2003 Jun 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sorror ML, Maris MB, Sandmaier BM, Storer BE, Stuart MJ, Hegenbart U, Agura E, Chauncey TR, Leis J, Pulsipher M, McSweeney P, Radich JP, Bredeson C, Bruno B, Langston A, Loken MR, Al-Ali H, Blume KG, Storb R, Maloney DG. Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol. 2005 Jun 1;23(16):3819-29. Epub 2005 Apr 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Sorror ML, Storer BE, Sandmaier BM, Maris M, Shizuru J, Maziarz R, Agura E, Chauncey TR, Pulsipher MA, McSweeney PA, Wade JC, Bruno B, Langston A, Radich J, Niederwieser D, Blume KG, Storb R, Maloney DG. Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol. 2008 Oct 20;26(30):4912-20. Epub 2008 Sep 15. link to original article link to PMC article PubMed
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- EBMT-NMAM2000: Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Musto P, Beksac M, Bosi A, Milone G, Corradini P, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Gahrton G. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011 Aug 1;29(22):3016-22. Epub 2011 Jul 5. Erratum in: J Clin Oncol. 2011 Sep 20;29(27):3721. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Update: Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A, Greinix H, Volin L, Narni F, Carella AM, Beksac M, Bosi A, Milone G, Corradini P, Schönland S, Friberg K, van Biezen A, Goldschmidt H, de Witte T, Morris C, Niederwieser D, Garderet L, Kröger N; EBMT Chronic Malignancies Working Party Plasma Cell Disorders Subcommittee. Autologous/reduced-intensity allogeneic stem cell transplantation vs autologous transplantation in multiple myeloma: long-term results of the EBMT-NMAM2000 study. Blood. 2013 Jun 20;121(25):5055-63. Epub 2013 Mar 12. link to original article PubMed
- 9005-2003: Bornhäuser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schäfer-Eckart K, Holler E, Kröger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. Epub 2012 Sep 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00150878
- FHCRC 1813.00: Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hübel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. Epub 2013 Jun 11. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00075478
Fludarabine, Cyclophosphamide, TBI for dUCB or haploidentical transplant
dUCB: double Umbilical Cord Blood
Regimen variant #1, dUCB transplantation
Study | Dates of enrollment | Evidence |
---|---|---|
Brunstein et al. 2011 (BMT CTN 0604) | 2009-01 to 2010-03 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 40 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once on day -6
Radiotherapy
- Total body irradiation (TBI) 200 cGy once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
Supportive therapy
- Mesna (Mesnex) (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection."
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +1, continued until ANC greater than or equal to 2000/μL for 3 consecutive days
GVHD prophylaxis
- Mycophenolate mofetil (CellCept) by the following weight-based criteria:
- More than 50 kg: 1000 mg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
- Less than 50 kg: 15 mg/kg (route not specified) every 8 hours, starting on day -3 "and continuing until day +30 or 7 days after engraftment, whichever was later"
- Cyclosporine (route not specified) with a goal trough of 200 to 400 ng/mL (starting date not specified) until day +100. Patients without GVHD had their dose tapered by 10% each week starting on day +101, with discontinuation of cyclosporine A around day +180 to +200.
- Tacrolimus (Prograf) (route not specified) with a goal trough level of 5 to 10 ng/mL could be substituted for cyclosporine.
One course
Regimen variant #2, Haploidentical
Study | Dates of enrollment | Evidence |
---|---|---|
Brunstein et al. 2011 (BMT CTN 0603) | 2009-01 to 2010-03 | Phase 2 |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -6 to -2 (5 consecutive days)
- Cyclophosphamide (Cytoxan) 14.5 mg/kg IV once per day on days -6 and -5 (2 consecutive days)
Radiotherapy
- Total body irradiation (TBI) 200 cGy once on day -1
Immunotherapy
- Allogeneic stem cells transfused on day 0
Supportive therapy
- Mesna (Mesnex) (dose/route/schedule not specified) and "vigorous IV hydration for uroprotection."
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +5, continued until ANC greater than or equal to 1000/μL for 3 consecutive days
GVHD prophylaxis
- Cyclophosphamide (Cytoxan) 50 mg/kg IBW IV over 1 to 2 hours once per day on days +3 & +4, started 60 to 72 hours after marrow infusion
- Mycophenolate mofetil (CellCept) 15 mg/kg (maximum daily dose of 3000 mg; route not specified) every 8 hours, starting on day +5, continued until day +35 or longer at physician discretion if active GVHD was present
- Tacrolimus (Prograf) (route not specified) with a goal trough level of 5 to 10 ng/mL, starting on day +5, continued until day +180
One course
References
- BMT CTN 0603: Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; BMT CTN. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. Epub 2011 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00849147
- BMT CTN 0604: Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; BMT CTN. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. Epub 2011 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00864227
- BMT CTN 0501: Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, Walters M, Horowitz MM, Kurtzberg J; Blood and Marrow Transplant Clinical Trials Network. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014 Oct 30;371(18):1685-94. link to original article link to PMC article PubMed NCT00412360
- BMT CTN 1101: Fuchs EJ, O'Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, Devine S, Horowitz MM, Horwitz ME, Karanes C, Leifer E, Magenau JM, McGuirk JP, Morris LE, Rezvani AR, Jones RJ, Brunstein CG. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021 Jan 21;137(3):420-428. link to original article link to PMC article PubMed NCT01597778
- QoL analysis: El Jurdi N, Martens MJ, Brunstein CG, O'Donnell P, Lee SJ, D'Souza A, Logan B, Hong S, Singh AK, Sandhu K, Shapiro RM, Horowitz MM, Hamilton BK. Health-Related Quality of Life in Double Umbilical Cord Blood versus Haploidentical Marrow Transplantation: A Quality of Life Analysis Report of BMT CTN 1101. Transplant Cell Ther. 2023 Jul;29(7):467.e1-467.e5. Epub 2023 Apr 22. link to original article link to PMC article PubMed
Fludarabine & Melphalan
Flu-Mel: Fludarabine & Melphalan
Regimen variant #1, 90/140
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Masson et al. 2023 (CUTALLO) | 2016-06-01 to 2022-03-03 | Propensity score analysis (E-esc) | No transplant | Superior PFS (primary endpoint) Median PFS: 9 vs 3 mo (HR 0.38, 95% CI 0.21-0.69) |
Diseases Studied: Cutaneous T-cell lymphoma
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day for 3 days (days not specified)
- Melphalan (Alkeran) 140 mg/m2 IV once (day not specified)
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Cyclosporine started on day -1, tapered on day +90 if no GVHD
- Methotrexate (MTX) 15 mg/m2 IV once on day +1, then 10 mg/m2 IV once per day on days +3, +6, +11
One course
Regimen variant #2, 132/140
Study | Dates of enrollment | Evidence |
---|---|---|
Anderlini et al. 2008 | 2001-2005 | Phase 2 |
Diseases Studied: Classical Hodgkin lymphoma
Chemotherapy
- Fludarabine (Fludara) 33 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -3 & -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- ATG (type not specified) by the following donor-based criteria:
- Matched unrelated donor: 2 mg/kg IV once per day on days -4 to -2
- Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4 to 12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given).
- Methotrexate (MTX) 5 mg/m2 IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients)
One course
Regimen variant #3, 150/140
Study | Dates of enrollment | Evidence |
---|---|---|
Alvarez et al. 2006 | 1999-06 to 2004-01 | Prospective |
Sureda et al. 2011 (HDR-ALLO) | Not reported | Phase 2 |
Diseases Studied: Classical Hodgkin lymphoma
Note: Alvarez et al. 2006 began CsA on day -1 and did not give day +11 MTX.
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -8 to -4
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -3 & -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Recipients of stem cells from matched unrelated donors received:
- Alvarez et al. 2006: Antithymocyte globulin, rabbit ATG (Thymoglobulin) 2.5 mg/kg IV once per day on days -4 to -2
- HDR-ALLO: ATG (type not specified) 45 mg/kg IV once per day on days -4 to -2
- Cyclosporine starting on day -2 at 1.5 mg/kg IV twice per day
- If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +150 (Alvarez et al. 2006) or +180 (HDR-ALLO).
- Methotrexate (MTX) 10 mg/m2 IV once per day on days +1, +3, +6, +11
One course
Regimen variant #4, 150/40, with alemtuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Peggs et al. 2005 | 1997-10-3 to 2003-08-21 | Non-randomized |
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -7 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
One course
References
- Peggs KS, Hunter A, Chopra R, Parker A, Mahendra P, Milligan D, Craddock C, Pettengell R, Dogan A, Thomson KJ, Morris EC, Hale G, Waldmann H, Goldstone AH, Linch DC, Mackinnon S. Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet. 2005 Jun 4-10;365(9475):1934-41. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed Hodgkin lymphoma: results of a Spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated MD Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- HDR-ALLO: Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N; GEL/TAMO. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma: results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed
- CUTALLO: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussière-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marçais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socié G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Français d'Etude des Lymphomes Cutanés; Société Française de Greffe de Moëlle et Thérapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. Epub 2023 Apr 24. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT02520908
Low-dose TBI
TBI: Total Body Irradiation
Regimen
Study | Evidence |
---|---|
Gyukocza et al. 2010 | Non-randomized |
Radiotherapy
- Total body irradiation (TBI) 200 cGy at a rate of 0.07 to 0.2000 cGy/min on day 0
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- One of the following (further details not specified):
- Mycophenolate mofetil (CellCept)
One course
References
- Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, Langston AA, Pulsipher MA, Bredeson CN, Maziarz RT, Bruno B, Petersen FB, Maris MB, Agura E, Yeager A, Bethge W, Sahebi F, Appelbaum FR, Maloney DG, Sandmaier BM. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010 Jun 10;28(17):2859-67. Epub 2010 May 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
TLI
TLI: Total Lymphocyte Irradiation
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Lowsky et al. 2005 | 2001-12-28 to 2004-12-01 | Non-randomized |
Kohrt et al. 2009 (BMT153) | 2001-12-28 to 2007-09-06 | Non-randomized |
Note: the schedule for TLI in BMT153 is slightly different, although the manuscript states that the protocol from Lowsky et al. 2005 was followed. See paper for details.
Radiotherapy
- TLI 800 cGy once per day on days -11 to -1 (10 fractions)
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) 1.5 mg/kg IV once per day on days -11 to -7
Immunotherapy
- Allogeneic stem cells transfused on day 0
One course
References
- Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. Erratum in: N Engl J Med. 2006 Feb 23;354(8):884. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BMT153: Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. Epub 2009 May 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00185640
(90)YFC
(90)YFC: Ibritumomab tiuxetan, Fludarabine, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Khouri et al. 2001 (MDACC ID01-233) | 1997-2000 | Phase 2 |
Note: this regimen is specifically addressed in the 2012 update.
Targeted therapy
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -14 & -7
Radioconjugate therapy
- Ibritumomab tiuxetan & Indium-111 5 mCi IV once on day -14 for dosimetry
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV once on day -7
Chemotherapy
- Fludarabine (Fludara) 30 mg/m2 IV once per day on days -5 to -3
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days -5 to -3
Immunotherapy
- Allogeneic stem cells transfused on day 0
GVHD prophylaxis
- Antithymocyte globulin, rabbit ATG (Thymoglobulin) by the following donor-based criteria:
- Matched unrelated or mismatched donors: 1 mg/kg IV once per day on days -2 & -1
- Tacrolimus (Prograf)
- Methotrexate (MTX)
One course
References
- MDACC ID01-233: Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. link to original article PubMed NCT00048737
- Update: Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- Update: Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed