Difference between revisions of "Autologous HSCT"
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− | + | <span id="BackToTop"></span> | |
− | + | <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 autologous 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 autologous HSCT outside of hematology/oncology but these use cases are considered to be out of scope. | |
− | |} | + | |
− | Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is a gathering point for all autologous 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: |
+ | *'''[[Stem cell mobilization]]''' | ||
+ | |||
+ | |||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
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=High dose therapy conditioning regimens, all lines of therapy= | =High dose therapy conditioning regimens, all lines of therapy= | ||
==BCNU/TT {{#subobject:a7b7ae|Regimen=1}}== | ==BCNU/TT {{#subobject:a7b7ae|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BCNU/TT: '''<u>BCNU</u>''' (Carmustine), '''<u>T</u>'''hio'''<u>T</u>'''epa | BCNU/TT: '''<u>BCNU</u>''' (Carmustine), '''<u>T</u>'''hio'''<u>T</u>'''epa | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:81ede7|Variant=1}}=== | ===Regimen variant #1 {{#subobject:81ede7|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/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | |[https://doi.org/10.1200/jco.2006.06.2117 Illerhaus et al. 2006] | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=81ede7 /> | <section begin=81ede7 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 50 | *[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 50 | ||
*[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) once per day on days 51 & 52 | *[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) once per day on days 51 & 52 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 56 |
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] starting on day 61, continued until WBC greater than 1 x 10<sup>9</sup>/L for 3 days | *[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] starting on day 61, continued until WBC greater than 1 x 10<sup>9</sup>/L for 3 days | ||
*"Standard supportive measures were taken according to institutional guidelines." | *"Standard supportive measures were taken according to institutional guidelines." | ||
− | + | '''One course''' | |
− | ''' | + | </div> |
<section end=81ede7 /> | <section end=81ede7 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:769950|Variant=1}}=== | ===Regimen variant #2 {{#subobject:769950|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/10.3324/haematol.11771 Illerhaus et al. 2008] |
− | | style="background-color:#ffffbe" |Pilot, | + | | style="background-color:#ffffbe" |Pilot, fewer than 20 pts |
|- | |- | ||
|} | |} | ||
<section begin=769950 /> | <section begin=769950 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 400 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) twice per day on days 2 & 3 | *[[Thiotepa (Thioplex)]] 5 mg/kg (route not specified) twice per day on days 2 & 3 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 7 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=769950 /> | <section end=769950 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | # Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16864853/ PubMed] | |
− | # Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. [https://doi.org/10.1200/jco.2006.06.2117 link to original article] ''' | + | # Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. [https://doi.org/10.3324/haematol.11771 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18166803/ PubMed] |
− | # Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. [ | ||
− | |||
==BEAC {{#subobject:60921c|Regimen=1}}== | ==BEAC {{#subobject:60921c|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BEAC: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''yclophosphamide | BEAC: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''yclophosphamide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:1a6845|Variant=1}}=== | ===Regimen variant #1 {{#subobject:1a6845|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ Geisler et al. 2008 (NLG MCL2)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ Geisler et al. 2008 (NLG MCL2)] | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=1a6845 /> | <section begin=1a6845 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
Line 85: | Line 85: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=1a6845 /> | <section end=1a6845 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:728b1c|Variant=1}}=== | ===Regimen variant #2 {{#subobject:728b1c|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/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)] |
|1987-1994 | |1987-1994 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Diffuse_large_B-cell_lymphoma#DHAP|DHAP]] x 4 | |[[Diffuse_large_B-cell_lymphoma#DHAP|DHAP]] x 4 | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 102: | Line 108: | ||
|} | |} | ||
<section begin=728b1c /> | <section begin=728b1c /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 | ||
Line 107: | Line 114: | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 2 to 5 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV over 30 minutes twice per day on days 2 to 5 | ||
*[[Cyclophosphamide (Cytoxan)]] 35 mg/kg IV over 60 minutes once per day on days 2 to 5 | *[[Cyclophosphamide (Cytoxan)]] 35 mg/kg IV over 60 minutes once per day on days 2 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Mesna (Mesnex)]] 8.3 mg/kg IV over 30 minutes every 4 hours on days 2 to 5 (optional) | *[[Mesna (Mesnex)]] 8.3 mg/kg IV over 30 minutes every 4 hours on days 2 to 5 (optional) | ||
− | + | *[[Autologous stem cells]] re-infused on day 7, given 48 hours after last dose of etoposide | |
− | + | '''One course''' | |
+ | </div> | ||
<section end=728b1c /> | <section end=728b1c /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:a5ff49|Variant=1}}=== | ===Regimen variant #3 {{#subobject:a5ff49|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.V77.7.1587.1587 Philip et al. 1991 (PARMA pilot)] |
− | | style="background-color:#91cf61" | | + | | style="background-color:#91cf61" |Non-randomized |
|- | |- | ||
|} | |} | ||
<section begin=a5ff49 /> | <section begin=a5ff49 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day -13 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day -13 | ||
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*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days -12 to -9 | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days -12 to -9 | ||
*[[Cyclophosphamide (Cytoxan)]] 35 mg/kg IV over 60 minutes once per day on days -12 to -9 | *[[Cyclophosphamide (Cytoxan)]] 35 mg/kg IV over 60 minutes once per day on days -12 to -9 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
*[[Mesna (Mesnex)]] 50 mg/kg IV once per day on days -12 to -9 (optional) | *[[Mesna (Mesnex)]] 50 mg/kg IV once per day on days -12 to -9 (optional) | ||
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
− | + | '''One course''' | |
+ | </div> | ||
<section end=a5ff49 /> | <section end=a5ff49 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''PARMA pilot:''' Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. [ | + | # '''PARMA pilot:''' Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. [https://doi.org/10.1182/blood.V77.7.1587.1587 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2009374/ PubMed] |
− | # '''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https:// | + | # '''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://doi.org/10.1056/NEJM199512073332305 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7477169/ PubMed] |
− | # '''Retrospective:''' Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. [https://doi.org/10.1007/s00277-007-0360-0 link to original article] ''' | + | # '''Retrospective:''' Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. [https://doi.org/10.1007/s00277-007-0360-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17710401/ PubMed] |
− | # '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [ | + | # '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [https://doi.org/10.1182/blood-2008-03-147025 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18625886/ PubMed] |
− | |||
==BEAM {{#subobject:1e26e2|Regimen=1}}== | ==BEAM {{#subobject:1e26e2|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 300/100q12/100q12/140 with 24-hour rest {{#subobject:13246c|Variant=1}}=== | ===Regimen variant #1, 300/100q12/100q12/140 with 24-hour rest {{#subobject:13246c|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ Alvarnas et al. 2016 (BMT CTN 0803/AMC 071)] | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=13246c /> | <section begin=13246c /> | ||
+ | <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 | ||
Line 162: | Line 170: | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) | ||
*[[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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=13246c /> | <section end=13246c /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 300/100q12/100q12/140 with 48-hour rest {{#subobject:f28f87|Variant=1}}=== | ===Regimen variant #2, 300/100q12/100q12/140 with 48-hour rest {{#subobject:f28f87|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/10.1111/j.1365-2141.2008.07498.x Van 't Veer et al. 2008 (HOVON 45)] |
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=f28f87 /> | <section begin=f28f87 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | ||
Line 178: | Line 193: | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3 (total dose: 800 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3 (total dose: 800 mg/m<sup>2</sup>) | ||
*[[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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=f28f87 /> | <section end=f28f87 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 300/100q12/200/140 {{#subobject:76416d|Variant=1}}=== | ===Regimen variant #3, 300/100q12/200/140 {{#subobject:76416d|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/NEJM198706113162401 Philip et al. 1987] |
+ | |1980-1985 | ||
|style="background-color:#91cf61"|Non-randomized | |style="background-color:#91cf61"|Non-randomized | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: The manuscript did not specify which day peripheral blood stem cells were administered. This trial is of important historic interest because it indicated that patients with less than a partial response did worse than those with PR or better.'' |
<section begin=76416d /> | <section begin=76416d /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
Line 195: | Line 219: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV over 5 minutes once on day 6 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV over 5 minutes once on day 6 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=76416d /> | <section end=76416d /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 300/100q12/200q12/140 {{#subobject:16f7a3|Variant=1}}=== | ===Regimen variant #4, 300/100q12/200q12/140 {{#subobject:16f7a3|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/10.1200/jco.2003.05.024 Abrey et al. 2003] | |[https://doi.org/10.1200/jco.2003.05.024 Abrey et al. 2003] | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2005-12-4898 Stewart et al. 2006] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|[https://doi.org/10.1200/jco.2011.40.2719 d'Amore et al. 2012 (NLG-T-01)] | |[https://doi.org/10.1200/jco.2011.40.2719 d'Amore et al. 2012 (NLG-T-01)] | ||
− | | style="background-color:#91cf61" | | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=16f7a3 /> | <section begin=16f7a3 /> | ||
+ | <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 | ||
Line 217: | Line 248: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) | ||
*[[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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
*(described in some publications) | *(described in some publications) | ||
− | * | + | *[[Filgrastim (Neupogen)]] by the following weight-based criteria: |
− | * | + | **Less than 70 kg: 300 mcg SC once per day, starting on day +7 after stem cell transplant |
+ | **More than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): 480 mcg SC once per day, starting on day +7 after stem cell transplant | ||
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day on Monday and Thursdays, until 6 months after BEAM | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day on Monday and Thursdays, until 6 months after BEAM | ||
− | + | *[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day while ANC less than 500/μL | |
− | *[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day | ||
*Antifungal prophylaxis with one of the following: | *Antifungal prophylaxis with one of the following: | ||
− | **[[Fluconazole (Diflucan)]] 100 mg PO once per day | + | **[[Fluconazole (Diflucan)]] 100 mg PO once per day while ANC less than 500/μL |
− | **[[Mycostatin | + | **[[Nystatin (Mycostatin)]] 500,000 units swish & swallow four times per day while ANC less than 500/μL |
− | *[[Acyclovir (Zovirax)]] 400 mg PO three times per day | + | *[[Acyclovir (Zovirax)]] 400 mg PO three times per day while ANC less than 500/μL |
− | ''' | + | '''One course''' |
+ | </div> | ||
<section end=16f7a3 /> | <section end=16f7a3 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
===Regimen variant #5, 300/100q12/400/140 {{#subobject:2821aa|Variant=1}}=== | ===Regimen variant #5, 300/100q12/400/140 {{#subobject:2821aa|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ Geisler et al. 2008 (NLG MCL2)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ Geisler et al. 2008 (NLG MCL2)] | ||
− | |style="background-color:#91cf61"|Phase | + | |style="background-color:#91cf61"|Phase 2 |
|- | |- | ||
|} | |} | ||
''Paper did not specify which day peripheral blood stem cells were administered.'' | ''Paper did not specify which day peripheral blood stem cells were administered.'' | ||
<section begin=2821aa /> | <section begin=2821aa /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
Line 247: | Line 283: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days 2 to 5 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days 2 to 5 | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day 6 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day 6 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=2821aa /> | <section end=2821aa /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #6, 300/150q12/200q12/140 {{#subobject:5e3c75|Variant=1}}=== | ===Regimen variant #6, 300/150q12/200q12/140 {{#subobject:5e3c75|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 257: | Line 299: | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdi248 Josting et al. 2005] | |[https://doi.org/10.1093/annonc/mdi248 Josting et al. 2005] | ||
− | | | + | |Not reported |
− | | style="background-color:#91cf61" |Phase | + | | 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/S0140-6736(02)08938-9 Schmitz et al. 2002 (GHSG HD-R1)] |
|1993-1997 | |1993-1997 | ||
− | | style="background-color:#1a9851" | | + | | style="background-color:#1a9851" |Randomized (E-esc) |
− | |[[ | + | |[[Classical_Hodgkin_lymphoma#DexaBEAM|DexaBEAM]] |
| style="background-color:#91cf60" |Seems to have superior FFTF | | style="background-color:#91cf60" |Seems to have superior FFTF | ||
|- | |- | ||
Line 271: | Line 313: | ||
''Note: Josting et al. 2005 did not specify which day peripheral blood stem cells were administered.'' | ''Note: Josting et al. 2005 did not specify which day peripheral blood stem cells were administered.'' | ||
<section begin=5e3c75 /> | <section begin=5e3c75 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | ||
Line 276: | Line 319: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -7 to -4 (total dose: 1600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -7 to -4 (total dose: 1600 mg/m<sup>2</sup>) | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -3 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -3 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=5e3c75 /> | <section end=5e3c75 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #7, 300/200/100q12/140 {{#subobject:bbc83f|Variant=1}}=== | ===Regimen variant #7, 300/200/100q12/140 {{#subobject:bbc83f|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/10.1038/sj.bmt.1705452 Colombat et al. 2006] | |[https://doi.org/10.1038/sj.bmt.1705452 Colombat et al. 2006] | ||
− | | style="background-color:#91cf61" |Phase | + | |1999-07 to 2001-11 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | |||
<section begin=bbc83f /> | <section begin=bbc83f /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 1 | ||
Line 295: | Line 344: | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 2 to 5 (total dose: 800 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV every 12 hours on days 2 to 5 (total dose: 800 mg/m<sup>2</sup>) | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day 6 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day 6 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=bbc83f /> | <section end=bbc83f /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #8, 300/200/200/140 {{#subobject:c92668|Variant=1}}=== | ===Regimen variant #8, 300/200/200/140 {{#subobject:c92668|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" 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/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)] | ||
− | | style="background-color:#91cf61" |Non-randomized | + | |2003-2007 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
<section begin=c92668 /> | <section begin=c92668 /> | ||
+ | <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 | ||
Line 311: | Line 369: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV once per day on days -5 to -2 | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV once 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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=c92668 /> | <section end=c92668 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
===Regimen variant #9, 300/200/200q12/140 with 24 hour rest {{#subobject:fa5ca4|Variant=1}}=== | ===Regimen variant #9, 300/200/200q12/140 with 24 hour rest {{#subobject:fa5ca4|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/10.1002/cncr.27418 Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)] |
− | | | + | |Not reported |
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#Z-BEAM|Z-BEAM]] | |[[#Z-BEAM|Z-BEAM]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1111/bjh.13036 Pardal et al. 2014 (GELTAMO-2006)] | ||
+ | |2007-2009 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)] | |[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)] | ||
− | | | + | |2010-2013 |
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 334: | Line 405: | ||
|} | |} | ||
<section begin=fa5ca4 /> | <section begin=fa5ca4 /> | ||
+ | <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 | ||
Line 339: | Line 411: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) | ||
*[[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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
− | *Variously described | + | *Variously described: |
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4 "until engraftment" | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4 "until engraftment" | ||
*[[Valacyclovir (Valtrex)]] (dose not specified) for one month | *[[Valacyclovir (Valtrex)]] (dose not specified) for one month | ||
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/frequency not specified) for six months | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/frequency not specified) for six months | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=fa5ca4 /> | <section end=fa5ca4 /> | ||
− | + | </div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #10, 300/200/200q12/140 with 48 hour rest {{#subobject:fa5ca6|Variant=1}}=== | ===Regimen variant #10, 300/200/200q12/140 with 48 hour rest {{#subobject:fa5ca6|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/PMC9635528/ Schmitz et al. 2021 (MYS-07-HMO-CTIL)] |
|2011-2014 | |2011-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT | + | |[[Allogeneic_HSCT#Fludarabine.2C_Busulfan.2C_Cyclophosphamide|Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS36 | ||
|- | |- | ||
|} | |} | ||
<section begin=fa5ca6 /> | <section begin=fa5ca6 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | ||
Line 368: | Line 444: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3 (total dose: 1600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3 (total dose: 1600 mg/m<sup>2</sup>) | ||
*[[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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=fa5ca6 /> | <section end=fa5ca6 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #11, 300/200q12/200q12/140 {{#subobject:75447a|Variant=1}}=== | ===Regimen variant #11, 300/200q12/200q12/140 {{#subobject:75447a|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://haematologica.org/article/view/2730 Zinzani et al. 2003] |
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
<section begin=75447a /> | <section begin=75447a /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | ||
Line 384: | Line 467: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV twice per day on days -6 to -3 (total dose: 1600 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV twice per day on days -6 to -3 (total dose: 1600 mg/m<sup>2</sup>) | ||
*[[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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=75447a /> | <section end=75447a /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #12, 300/200/400/140 {{#subobject:d7b00a|Variant=1}}=== | ===Regimen variant #12, 300/200/400/140 {{#subobject:d7b00a|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| 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: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10. | + | |[https://doi.org/10.1016/j.annonc.2023.10.095 Ladetto et al. 2023 (FIL FLAZ12)] |
− | | style="background-color:# | + | |2012-08 to 2019-09 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Follicular_lymphoma#Ibritumomab_tiuxetan_protocol_3|Zevalin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
<section begin=d7b00a /> | <section begin=d7b00a /> | ||
+ | <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 | ||
Line 400: | Line 496: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -5 to -2 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once 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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day + | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +2, continued until ANC greater than 1500/μL |
− | + | '''One course''' | |
+ | </div> | ||
<section end=d7b00a /> | <section end=d7b00a /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. [https:// | + | # Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. [https://doi.org/10.1056/NEJM198706113162401 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/3295541/ PubMed] |
− | # '''GHSG HD-R1:''' Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065-71. [https:// | + | # '''GHSG HD-R1:''' Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065-71. [https://doi.org/10.1016/S0140-6736(02)08938-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12086759/ PubMed] |
− | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. [ | + | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. [https://haematologica.org/article/view/2730 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12745271/ PubMed] |
− | # Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. [https://doi.org/10.1200/jco.2003.05.024 link to original article] ''' | + | # Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. [https://doi.org/10.1200/jco.2003.05.024 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14615443/ PubMed] |
− | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, De Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Guidice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Marchi E, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience. Leuk Lymphoma. 2004 Feb;45(2):321-6. [https://pubmed.ncbi.nlm.nih.gov/15101718 PubMed] | + | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, De Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Guidice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Marchi E, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience. Leuk Lymphoma. 2004 Feb;45(2):321-6. [https://pubmed.ncbi.nlm.nih.gov/15101718/ PubMed] |
− | # Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. [https://doi.org/10.1093/annonc/mdi248 link to original article] ''' | + | # Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. [https://doi.org/10.1093/annonc/mdi248 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15939712/ PubMed] |
− | # Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. [ | + | # Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. [https://doi.org/10.1182/blood-2005-12-4898 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16467197/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] ''' | + | # Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. [https://doi.org/10.1038/sj.bmt.1705452 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16951691/ PubMed] |
− | # '''Retrospective:''' Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. [https://doi.org/10.1007/s00277-007-0360-0 link to original article] ''' | + | # '''Retrospective:''' Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. [https://doi.org/10.1007/s00277-007-0360-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17710401/ PubMed] |
− | # '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [ | + | # '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [https://doi.org/10.1182/blood-2008-03-147025 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18625886/ PubMed] ISRCTN87866680 |
− | # '''HOVON 45:''' Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. [https:// | + | # '''HOVON 45:''' Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. [https://doi.org/10.1111/j.1365-2141.2008.07498.x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19036081/ PubMed] |
− | + | # '''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [https://doi.org/10.1200/jco.2010.28.1618 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20660832/ PubMed] [https://clinicaltrials.gov/study/NCT00137995 NCT00137995] | |
− | + | # '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://doi.org/10.1002/cncr.27418 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22252613/ PubMed] [https://clinicaltrials.gov/study/NCT00491491 NCT00491491] | |
− | # '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https:// | + | # '''NLG-T-01:''' d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. [https://doi.org/10.1200/jco.2011.40.2719 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22851556/ PubMed] [https://clinicaltrials.gov/study/NCT00791947 NCT00791947] |
− | + | # '''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://doi.org/10.1111/bjh.13036 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25066542/ PubMed] [https://clinicaltrials.gov/study/NCT01361191 NCT01361191] | |
− | + | # '''BMT CTN 0803/AMC 071:''' Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. [https://doi.org/10.1182/blood-2015-08-664706 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000843/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27297790/ PubMed] [https://clinicaltrials.gov/study/NCT01141712 NCT01141712] | |
− | + | # '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28029326/ PubMed] [https://clinicaltrials.gov/study/NCT01014208 NCT01014208] | |
− | # '''BMT CTN 0803/AMC 071:''' Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. [ | + | # '''MYS-07-HMO-CTIL:''' Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. [https://doi.org/10.1182/blood.2020008825 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9635528/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33512419/ PubMed] [https://clinicaltrials.gov/study/NCT00984412 NCT00984412] |
− | # '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab | + | #'''FIL FLAZ12:''' Ladetto M, Tavarozzi R, Zanni M, Evangelista A, Ferrero S, Tucci A, Botto B, Bolis S, Volpetti S, Zilioli VR, Puccini B, Arcari A, Pavone V, Gaidano G, Corradini P, Tani M, Cavallo F, Milone G, Ghiggi C, Pinto A, Pastore D, Ferreri AJM, Latte G, Patti C, Re F, Benedetti F, Luminari S, Pennese E, Bossi E, Boccomini C, Anastasia A, Bottelli C, Ciccone G, Vitolo U. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial. Ann Oncol. 2024 Jan;35(1):118-129. Epub 2023 Nov 3. [https://doi.org/10.1016/j.annonc.2023.10.095 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37922989/ PubMed] [https://clinicaltrials.gov/study/NCT01827605 NCT01827605] |
− | |||
==BeEAM {{#subobject:dee72f|Regimen=1}}== | ==BeEAM {{#subobject:dee72f|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BeEAM: '''<u>Be</u>'''ndamustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | BeEAM: '''<u>Be</u>'''ndamustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:81ff2e|Variant=1}}=== | ===Regimen {{#subobject:81ff2e|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-2011-04-351924 Visani et al. 2011] |
− | | style="background-color:#91cf61" |Phase | + | |2008-08 to 2010-06 |
+ | | style="background-color:#91cf61" |Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
<section begin=81ff2e /> | <section begin=81ff2e /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Bendamustine]] 200 mg/m<sup>2</sup> IV once per day on days -7 & -6 | *[[Bendamustine]] 200 mg/m<sup>2</sup> IV once per day on days -7 & -6 | ||
Line 449: | Line 545: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -5 to -2 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once 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 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=81ff2e /> | ||
+ | </div> | ||
− | |||
− | |||
===References=== | ===References=== | ||
− | # Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. [ | + | # Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. [https://doi.org/10.1182/blood-2011-04-351924 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21816830/ PubMed] EudraCT 2008-002736-15 |
==Bortezomib & Melphalan {{#subobject:9c28bc|Regimen=1}}== | ==Bortezomib & Melphalan {{#subobject:9c28bc|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bor-HDM: '''<u>Bor</u>'''tezomib, '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>M</u>'''elphalan | Bor-HDM: '''<u>Bor</u>'''tezomib, '''<u>H</u>'''igh '''<u>D</u>'''ose '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, HDM 140 mg/m<sup>2</sup> {{#subobject:c0ec02|Variant=1}}=== | ===Regimen variant #1, HDM 140 mg/m<sup>2</sup> {{#subobject:c0ec02|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/10.1016/j.bbmt.2015.04.001 Sanchorawala et al. 2015 (X05292)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=c0ec02 /> | <section begin=c0ec02 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV once per day on days -6, -3, +1, +4 | *[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV once per day on days -6, -3, +1, +4 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -2 & -1 | *[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV once per day on days -2 & -1 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=c0ec02 /> | <section end=c0ec02 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, HDM 200 mg/m<sup>2</sup> {{#subobject:0bfd33|Variant=1}}=== | ===Regimen variant #2, HDM 200 mg/m<sup>2</sup> {{#subobject:0bfd33|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-2009-06-229658 Roussel et al. 2009] |
− | | style="background-color:#91cf61" |Phase | + | |2007-07 to 2007-12 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.bbmt.2015.04.001 Sanchorawala et al. 2015 (X05292)] |
− | | style="background-color:#91cf61" |Phase | + | |2010-01 to 2013-08 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin=0bfd33 /> | <section begin=0bfd33 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV once per day on days -6, -3, +1, +4 | *[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> IV once per day on days -6, -3, +1, +4 | ||
Line 496: | Line 602: | ||
*[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -2 & -1 | *[[Melphalan (Alkeran)]] 100 mg/m<sup>2</sup> IV once per day on days -2 & -1 | ||
**Roussel et al. 2009 gave as a single 200 mg/m<sup>2</sup> dose on day -2 | **Roussel et al. 2009 gave as a single 200 mg/m<sup>2</sup> dose on day -2 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=0bfd33 /> | <section end=0bfd33 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. [ | + | # Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. [https://doi.org/10.1182/blood-2009-06-229658 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19884643/ PubMed] [https://clinicaltrials.gov/study/NCT00642395 NCT00642395] |
− | # '''X05292:''' Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. [ | + | # '''X05292:''' Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. [https://doi.org/10.1016/j.bbmt.2015.04.001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25858810/ PubMed] [https://clinicaltrials.gov/study/NCT01083316 NCT01083316] |
− | |||
==Busulfan & Cyclophosphamide {{#subobject:9acbe9|Regimen=1}}== | ==Busulfan & Cyclophosphamide {{#subobject:9acbe9|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | BuCy: '''<u>Bu</u>'''sulfan & '''<u>Cy</u>'''clophosphamide |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 12.8/120 {{#subobject:6mmf66|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/10.1002/ajh.26800 Liu et al. 2023] | ||
+ | |2016-01 to 2019-02 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Ida-BuCy_999|Ida-BuCy]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of RR | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen variant # | + | <section begin=6mmf66 /> |
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Busulfan (Myleran)]] 3.2 mg/kg/day (route/frequency not specified) on days -7 to -4 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=6mmf66 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 16/120 {{#subobject:6ccf66|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2011-07-370247 Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42)] |
|1995-2006 | |1995-2006 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Acute_myeloid_leukemia#Etoposide_.26_Mitoxantrone|Etoposide & Mitoxantrone]] | |[[Acute_myeloid_leukemia#Etoposide_.26_Mitoxantrone|Etoposide & Mitoxantrone]] | ||
− | | style="background-color:#d9ef8b" |Might have superior RFS | + | | style="background-color:#d9ef8b" |Might have superior RFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
<section begin=6ccf66 /> | <section begin=6ccf66 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 4 mg/kg PO (frequency not specified) on days -7 to -4 | *[[Busulfan (Myleran)]] 4 mg/kg PO (frequency not specified) on days -7 to -4 | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=6ccf66 /> | <section end=6ccf66 /> | ||
− | ===Regimen variant # | + | </div><br> |
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #3, 16/200 {{#subobject:5d4efb|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 | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199605303342203 Ravindranath et al. 1996] |
|1988-1993 | |1988-1993 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|Intensive chemotherapy | |Intensive chemotherapy | ||
− | | style="background-color:#ffffbf" |Did not meet primary endpoint of | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS24 |
|- | |- | ||
|} | |} | ||
<section begin=5d4efb /> | <section begin=5d4efb /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -9 to -6 | *[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -9 to -6 | ||
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days -5 to -2 | *[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV once per day on days -5 to -2 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=5d4efb /> | <section end=5d4efb /> | ||
+ | </div> | ||
+ | |||
===References=== | ===References=== | ||
− | # Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. [https:// | + | # Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. [https://doi.org/10.1056/NEJM199605303342203 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8618581/ PubMed] |
− | # '''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [ | + | # '''HOVON-SAKK AML-29/AML-42:''' Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. [https://doi.org/10.1182/blood-2011-07-370247 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21951683/ PubMed] |
+ | #Liu H, Huang F, Zhang Y, Wu M, Xu N, Fan Z, Sun Z, Li X, Lin D, Xiong Y, Liu X, Lin R, Shi P, Xu J, Wang Z, Li X, Sun J, Liu Q, Xuan L. Idarubicin plus BuCy versus BuCy conditioning regimens for intermediate-risk acute myeloid leukemia in first complete remission undergoing auto-HSCT: An open-label, multicenter, randomized phase 3 trial. Am J Hematol. 2023 Mar;98(3):408-412. Epub 2023 Jan 1. [https://doi.org/10.1002/ajh.26800 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36588387/ PubMed] [https://clinicaltrials.gov/study/NCT02671708 NCT02671708] | ||
==Busulfan & Melphalan {{#subobject:484436|Regimen=1}}== | ==Busulfan & Melphalan {{#subobject:484436|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
BuMel: '''<u>Bu</u>'''sulfan & '''<u>Mel</u>'''phalan | BuMel: '''<u>Bu</u>'''sulfan & '''<u>Mel</u>'''phalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, PO busulfan (12 mg/kg) {{#subobject:c5fc8f|Variant=1}}=== | ===Regimen variant #1, PO busulfan (12 mg/kg) {{#subobject:c5fc8f|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-2012-11-466862 Yanada et al. 2013 (JALSG APL205R)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
''This regimen was evaluated in the setting of relapsed [[acute promyelocytic leukemia]].'' | ''This regimen was evaluated in the setting of relapsed [[acute promyelocytic leukemia]].'' | ||
<section begin=c5fc8f /> | <section begin=c5fc8f /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -6 to -4 (total dose of 12 mg/kg) | *[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -6 to -4 (total dose of 12 mg/kg) | ||
*[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV bolus once per day on days -3 & -2 | *[[Melphalan (Alkeran)]] 70 mg/m<sup>2</sup> IV bolus once per day on days -3 & -2 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=c5fc8f /> | <section end=c5fc8f /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, PO busulfan (16 mg/kg), mel 140 mg/m<sup>2</sup> {{#subobject:75d2e0|Variant=1}}=== | ===Regimen variant #2, PO busulfan (16 mg/kg), mel 140 mg/m<sup>2</sup> {{#subobject:75d2e0|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 584: | Line 734: | ||
|- | |- | ||
|[https://doi.org/10.1038/sj.bmt.1700992 Atra et al. 1997] | |[https://doi.org/10.1038/sj.bmt.1700992 Atra et al. 1997] | ||
− | | | + | |Not reported |
− | | style="background-color:#ffffbe" |Phase | + | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 591: | Line 741: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209090/ Whelan et al. 2018 (R2Loc)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209090/ Whelan et al. 2018 (R2Loc)] | ||
|2000-2015 | |2000-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Ewing_sarcoma#VAI|VAI]] | |[[Ewing_sarcoma#VAI|VAI]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint) |
|- | |- | ||
|} | |} | ||
''This regimen was evaluated in the setting of poor risk [[Ewing sarcoma]].'' | ''This regimen was evaluated in the setting of poor risk [[Ewing sarcoma]].'' | ||
<section begin=75d2e0 /> | <section begin=75d2e0 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg) | *[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg) | ||
*[[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 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=75d2e0 /> | <section end=75d2e0 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, PO busulfan (16 mg/kg), mel 160 mg/m<sup>2</sup> {{#subobject:75d2e1|Variant=1}}=== | ===Regimen variant #3, PO busulfan (16 mg/kg), mel 160 mg/m<sup>2</sup> {{#subobject:75d2e1|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/10.1038/sj.bmt.1700992 Atra et al. 1997] | |[https://doi.org/10.1038/sj.bmt.1700992 Atra et al. 1997] | ||
− | | style="background-color:#ffffbe" |Phase | + | |Not reported |
+ | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
''This regimen was evaluated in the setting of poor risk [[Ewing sarcoma]].'' | ''This regimen was evaluated in the setting of poor risk [[Ewing sarcoma]].'' | ||
<section begin=75d2e1 /> | <section begin=75d2e1 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg) | *[[Busulfan (Myleran)]] 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg) | ||
*[[Melphalan (Alkeran)]] 160 mg/m<sup>2</sup> IV once on day -1 | *[[Melphalan (Alkeran)]] 160 mg/m<sup>2</sup> IV once on day -1 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=75d2e1 /> | <section end=75d2e1 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, IV busulfan {{#subobject:a61951|Variant=1}}=== | ===Regimen variant #4, IV busulfan {{#subobject:a61951|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/10.1200/jco.2003.04.106 Strauss et al. 2003] | |[https://doi.org/10.1200/jco.2003.04.106 Strauss et al. 2003] | ||
− | | style="background-color:#91cf61" |Phase | + | |1998-01 to 1999-06 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
''This regimen was evaluated in the setting of metastatic [[Ewing sarcoma]]. Note that melphalan is reported as given on day 2 (not day -2) in the original reference but this is surely an error.'' | ''This regimen was evaluated in the setting of metastatic [[Ewing sarcoma]]. Note that melphalan is reported as given on day 2 (not day -2) in the original reference but this is surely an error.'' | ||
<section begin=a61951 /> | <section begin=a61951 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 150 mg/m<sup>2</sup> IV once per day on days -6 to -3 | *[[Busulfan (Myleran)]] 150 mg/m<sup>2</sup> IV once per day on days -6 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 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=a61951 /> | <section end=a61951 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR. High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma. Bone Marrow Transplant. 1997 Nov;20(10):843-6. [https://doi.org/10.1038/sj.bmt.1700992 link to original article] ''' | + | # Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR. High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma. Bone Marrow Transplant. 1997 Nov;20(10):843-6. [https://doi.org/10.1038/sj.bmt.1700992 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9404924/ PubMed] |
− | # Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for Ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. [https://doi.org/10.1200/jco.2003.04.106 link to original article] ''' | + | # Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for Ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. [https://doi.org/10.1200/jco.2003.04.106 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12885818/ PubMed] |
− | # '''JALSG APL205R:''' Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. [ | + | # '''JALSG APL205R:''' Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. [https://doi.org/10.1182/blood-2012-11-466862 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23412094/ PubMed] [https://clinicaltrials.gov/study/NCT01908621 NCT01908621] |
− | # '''R2Loc:''' Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Juergens H, Oberlin O; Euro-EWING-99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-EWING99 and Ewing-2008. J Clin Oncol. 2018 Nov 1;36(31):3110-9. Epub 2018 Sep 6. [https://doi.org/10.1200/JCO.2018.78.2516 link to original article] ''' | + | # '''R2Loc:''' Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Juergens H, Oberlin O; Euro-EWING-99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-EWING99 and Ewing-2008. J Clin Oncol. 2018 Nov 1;36(31):3110-9. Epub 2018 Sep 6. [https://doi.org/10.1200/JCO.2018.78.2516 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209090/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30188789/ PubMed] [https://clinicaltrials.gov/study/NCT00020566 NCT00020566] |
==Bu/TT {{#subobject:e04a91|Regimen=1}}== | ==Bu/TT {{#subobject:e04a91|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bu/TT: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa | Bu/TT: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:df1bb4|Variant=1}}=== | ===Regimen {{#subobject:df1bb4|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/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | |[https://doi.org/10.1093/annonc/mdl458 Montemurro et al. 2007 (OSHO-53)] | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=df1bb4 /> | <section begin=df1bb4 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Busulfan (Myleran)]] 4 mg/kg PO four times per day on days -8 to -5 | *[[Busulfan (Myleran)]] 4 mg/kg PO four times per day on days -8 to -5 | ||
*[[Thiotepa (Thioplex)]] 5 mg/kg IV once per day on days -4 & -3 | *[[Thiotepa (Thioplex)]] 5 mg/kg IV once per day on days -4 & -3 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=df1bb4 /> | <section end=df1bb4 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''OSHO-53:''' Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. [https://doi.org/10.1093/annonc/mdl458 link to original article] ''' | + | # '''OSHO-53:''' Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. [https://doi.org/10.1093/annonc/mdl458 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17185743/ PubMed] |
− | |||
==Bu/TT/Cy {{#subobject:e04a91|Regimen=1}}== | ==Bu/TT/Cy {{#subobject:e04a91|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | Bu/TT/Cy: '''<u>Bu</u>'''sulfan, '''<u>T</u>'''hio'''<u>T</u>'''epa, '''<u>Cy</u>'''clophosphamide | ||
<br>TBC: '''<u>T</u>'''hiotepa, '''<u>B</u>'''usulfan, , '''<u>Cy</u>'''clophosphamide | <br>TBC: '''<u>T</u>'''hiotepa, '''<u>B</u>'''usulfan, , '''<u>Cy</u>'''clophosphamide | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:df1bb4|Variant=1}}=== | ===Regimen {{#subobject:df1bb4|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://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ Omuro et al. 2015 (MSK 04-129)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
''Primary indication: [[CNS lymphoma|primary CNS lymphoma (PCNSL)]]'' | ''Primary indication: [[CNS lymphoma|primary CNS lymphoma (PCNSL)]]'' | ||
− | <section begin= | + | <section begin=df1bb5 /> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> IV once per day on days -9, -8, and -7 | *[[Thiotepa (Thioplex)]] 250 mg/m<sup>2</sup> IV once per day on days -9, -8, and -7 | ||
*[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -6, -5, and -4 | *[[Busulfan (Myleran)]] 3.2 mg/kg IV once per day on days -6, -5, and -4 | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 and -2 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 and -2 | ||
− | <section end= | + | ====Supportive therapy==== |
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=df1bb5 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. [ | + | # '''MSK 04-129:''' Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. [https://doi.org/10.1182/blood-2014-10-604561 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342354/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25568347/ PubMed] [https://clinicaltrials.gov/study/NCT00596154 NCT00596154] |
− | # '''Retrospective:''' DeFilipp Z, Li S, El-Jawahri A, Armand P, Nayak L, Wang N, Batchelor TT, Chen YB. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017 Aug 15;123(16):3073-3079. Epub 2017 Apr 3. [https:// | + | # '''Retrospective:''' DeFilipp Z, Li S, El-Jawahri A, Armand P, Nayak L, Wang N, Batchelor TT, Chen YB. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017 Aug 15;123(16):3073-3079. Epub 2017 Apr 3. [https://doi.org/10.1002/cncr.30695 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28369839/ PubMed] |
==CBV {{#subobject:935235|Regimen=1}}== | ==CBV {{#subobject:935235|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CBV: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide) | CBV: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 100/300/60, some BSA-based {{#subobject:6fc278|Variant=1}}=== | ===Regimen variant #1, 100/300/60, some BSA-based {{#subobject:6fc278|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 712: | Line 880: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)] | ||
|1999-2007 | |1999-2007 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#R-CHOP|R-CHOP]] x 8 | |[[#R-CHOP|R-CHOP]] x 8 | ||
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior PFS24 (co-primary endpoint)<br>PFS24: 69% vs 55%<br>(HR 0.58, 95% CI 0.40-0.85)<br><br>Did not meet co-primary endpoint of OS24<br>OS24: 74% vs 71%<br>(HR 1.26, 95% CI 0.82-1.94) |
|- | |- | ||
|} | |} | ||
<section begin=6fc278 /> | <section begin=6fc278 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 100 mg/kg (IBW) IV once on day -2 | *[[Cyclophosphamide (Cytoxan)]] 100 mg/kg (IBW) IV once on day -2 | ||
*[[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)]] 60 mg/kg (IBW) IV once on day -4 | *[[Etoposide (Vepesid)]] 60 mg/kg (IBW) IV once on day -4 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=6fc278 /> | <section end=6fc278 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 100/15/60, all weight-based {{#subobject:35a696|Variant=1}}=== | ===Regimen variant #2, 100/15/60, all weight-based {{#subobject:35a696|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/10.1200/jco.1998.16.1.48 Stiff et al. 1998] | |[https://doi.org/10.1200/jco.1998.16.1.48 Stiff et al. 1998] | ||
− | | style="background-color:#91cf61" |Phase | + | |1990-1994 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793032/ Damon et al. 2009 (CALGB 59909)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793032/ Damon et al. 2009 (CALGB 59909)] | ||
− | | style="background-color:#91cf61" |Phase | + | |2001-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Stiff et al. 1998 based BCNU dosing on ideal body weight, whereas CALGB 59909 capped based on BSA, as described below.'' | ||
<section begin=35a696 /> | <section begin=35a696 /> | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 100 mg/kg IV over 2 hours once on day -2 | *[[Cyclophosphamide (Cytoxan)]] 100 mg/kg IV over 2 hours once on day -2 | ||
*[[Carmustine (BCNU)]] 15 mg/kg (maximum dose of 550 mg/m<sup>2</sup>) IV over 60 minutes once on day -6 | *[[Carmustine (BCNU)]] 15 mg/kg (maximum dose of 550 mg/m<sup>2</sup>) IV over 60 minutes once on day -6 | ||
*[[Etoposide (Vepesid)]] 60 mg/kg IV over 4 hours once on day -4 | *[[Etoposide (Vepesid)]] 60 mg/kg IV over 4 hours once on day -4 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4, to continue until ANC greater than 5000/ | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4, to continue until ANC greater than 5000/μL once or greater than 1500/μL twice |
− | *[[Levofloxacin (Levaquin)]] 500 mg PO once per day, starting on day +2, to continue until ANC at least 500/ | + | *[[Levofloxacin (Levaquin)]] 500 mg PO once per day, starting on day +2, to continue until ANC at least 500/μL |
− | *[[Fluconazole (Diflucan)]] 200 mg PO once per day, starting on day +1, to continue until ANC at least 500/ | + | *[[Fluconazole (Diflucan)]] 200 mg PO once per day, starting on day +1, to continue until ANC at least 500/μL |
*[[Acyclovir (Zovirax)]] 200 mg PO three times per day, starting on day -2, to continue until 1 year after HSCT | *[[Acyclovir (Zovirax)]] 200 mg PO three times per day, starting on day -2, to continue until 1 year after HSCT | ||
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day on Saturday and Sunday, to continue until 3 months after HSCT | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day on Saturday and Sunday, to continue until 3 months after HSCT | ||
− | + | =====Additional considerations===== | |
− | ''' | + | If any patient appeared to be experiencing carmustine-induced pneumonitis: |
+ | *[[Prednisone (Sterapred)]] 0.5 mg/kg PO twice per day x 2 weeks, then tapered over 4 weeks | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=35a696 /> | <section end=35a696 /> | ||
− | + | </div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1500/300/250, all BSA-based {{#subobject:1ba6d|Variant=1}}=== | ===Regimen variant #3, 1500/300/250, all BSA-based {{#subobject:1ba6d|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://haematologica.org/article/view/2730 Zinzani et al. 2003] |
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
<section begin=1ba6d /> | <section begin=1ba6d /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once per day on days -6 to -3 | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once per day on days -6 to -3 | ||
*[[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)]] 250 mg/m<sup>2</sup> IV once per day on days -6 to -4 | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once per day on days -6 to -4 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=1ba6d /> | <section end=1ba6d /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 1800/600/400 {{#subobject:cf6828|Variant=1}}=== | ===Regimen variant #4, 1800/600/400 {{#subobject:cf6828|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.V83.5.1193.1193 Reece et al. 1994] |
− | | style="background-color:#ffffbe" |Phase | + | |1985-1988 |
+ | | style="background-color:#ffffbe" |Phase 2, fewer than 20 pts | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: the lower of IBW or ABW was used in the dosing calculations.'' | ||
<section begin=cf6828 /> | <section begin=cf6828 /> | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1800 mg/m<sup>2</sup> IV over 2 hours once per day on days -7 to -4 | *[[Cyclophosphamide (Cytoxan)]] 1800 mg/m<sup>2</sup> IV over 2 hours once per day on days -7 to -4 | ||
*[[Carmustine (BCNU)]] 600 mg/m<sup>2</sup> IV once on day -3 | *[[Carmustine (BCNU)]] 600 mg/m<sup>2</sup> IV once on day -3 | ||
*[[Etoposide (Vepesid)]] 400 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days -7 to -5 | *[[Etoposide (Vepesid)]] 400 mg/m<sup>2</sup> IV over 60 minutes every 12 hours on days -7 to -5 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=cf6828 /> | <section end=cf6828 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, Voss N, Chan KW, Phillips GL. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood. 1994 Mar 1;83(5):1193-9. [ | + | # Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, Voss N, Chan KW, Phillips GL. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood. 1994 Mar 1;83(5):1193-9. [https://doi.org/10.1182/blood.V83.5.1193.1193 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8118023/ PubMed] |
− | # Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [https://doi.org/10.1200/jco.1998.16.1.48 link to original article] ''' | + | # Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [https://doi.org/10.1200/jco.1998.16.1.48 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9440722/ PubMed] |
− | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. [ | + | # '''Retrospective:''' Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. [https://haematologica.org/article/view/2730 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12745271/ PubMed] |
− | # Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. [https://doi.org/10.1200/jco.2009.22.2554 link to original article] ''' | + | # '''CALGB 59909:''' Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. [https://doi.org/10.1200/jco.2009.22.2554 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19917845/ PubMed] [https://clinicaltrials.gov/study/NCT00020943 NCT00020943] |
− | # Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https:// | + | # '''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://doi.org/10.1056/NEJMoa1301077 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24171516/ PubMed] [https://clinicaltrials.gov/study/NCT00004031 NCT00004031] |
==CBV-Mx {{#subobject:77feb1|Regimen=1}}== | ==CBV-Mx {{#subobject:77feb1|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CBV-Mx: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide), '''<u>M</u>'''ito'''<u>x</u>'''antrone | CBV-Mx: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide), '''<u>M</u>'''ito'''<u>x</u>'''antrone | ||
− | ===Regimen {{#subobject:8271c4|Variant=1}}=== | + | <br>CBVM: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide), '''<u>M</u>'''itoxantrone |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | !style="width: | + | ===Regimen variant #1 {{#subobject:8271c4|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/10.1200/jco.2007.15.5887 Morschhauser et al. 2008 (GELA/SFGM H96)] | |[https://doi.org/10.1200/jco.2007.15.5887 Morschhauser et al. 2008 (GELA/SFGM H96)] | ||
− | | style="background-color:#91cf61" | | + | |1995-01 to 2002-12 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin=8271c4 /> | <section begin=8271c4 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day IV on days -7 to -4 | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day IV on days -7 to -4 | ||
Line 817: | Line 1,010: | ||
*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup>/day IV on days -7 to -4 | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup>/day IV on days -7 to -4 | ||
*[[Mitoxantrone (Novantrone)]] 30 mg/m<sup>2</sup> IV once on day -8 | *[[Mitoxantrone (Novantrone)]] 30 mg/m<sup>2</sup> IV once on day -8 | ||
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused on day 0 | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=8271c4 /> | <section end=8271c4 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:bbedec|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/10.1093/annonc/mdp237 Haioun et al. 2009 (LNH 98-3)] | ||
+ | |1999-2004 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <section begin=bbedec /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day IV on days 2 to 5 | ||
+ | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day 6 | ||
+ | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup>/day IV on days 2 to 5 | ||
+ | *[[Mitoxantrone (Novantrone)]] 45 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=bbedec /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''GELA/SFGM H96:''' Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA; SFGM. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. [https://doi.org/10.1200/jco.2007.15.5887 link to original article] ''' | + | # '''GELA/SFGM H96:''' Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA; SFGM. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. [https://doi.org/10.1200/jco.2007.15.5887 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19018090/ PubMed] |
− | ## '''Update:''' Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. [ | + | ## '''Update:''' Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. [https://doi.org/10.3324/haematol.2015.136408 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004408/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26721893/ PubMed] |
+ | #'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [https://doi.org/10.1093/annonc/mdp237 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19567453/ PubMed] [https://clinicaltrials.gov/study/NCT00169169 NCT00169169] | ||
==CHUT {{#subobject:e9e363|Regimen=1}}== | ==CHUT {{#subobject:e9e363|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:392c1c|Variant=1}}=== | ===Regimen {{#subobject:392c1c|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/10.1038/sj.bmt.1705935 Biron et al. 2007 (Pegase 03)] |
|1995-2001 | |1995-2001 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |No further treatment | + | |[[#Observation_888|No further treatment]] |
| style="background-color:#1a9850" |Superior DFS | | style="background-color:#1a9850" |Superior DFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This regimen is no longer used, but of historical interest.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup> | *[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup> | ||
*[[Thiotepa (Thioplex)]] 800 mg/m<sup>2</sup> | *[[Thiotepa (Thioplex)]] 800 mg/m<sup>2</sup> | ||
− | + | ====Supportive therapy==== | |
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''Pegase 03:''' Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. [https:// | + | # '''Pegase 03:''' Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. [https://doi.org/10.1038/sj.bmt.1705935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18037940/ PubMed] [https://clinicaltrials.gov/study/NCT00002870 NCT00002870] |
==CTCb {{#subobject:02f569|Regimen=1}}== | ==CTCb {{#subobject:02f569|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin | CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin | ||
− | + | <div class="toccolours" style="background-color:#ee6b6e"> | |
===Regimen {{#subobject:3dea9c|Variant=1}}=== | ===Regimen {{#subobject:3dea9c|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 869: | Line 1,088: | ||
|[https://doi.org/10.1200/jco.1990.8.7.1239 Eder et al. 1990] | |[https://doi.org/10.1200/jco.1990.8.7.1239 Eder et al. 1990] | ||
|1987-1988 | |1987-1988 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1/2 |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM200004133421501 Stadtmauer et al. 2000] |
|1990-1997 | |1990-1997 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Breast_cancer#CMF_2|CMF]] | |[[Breast_cancer#CMF_2|CMF]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(98)01350-6 Rodenhuis et al. 1998] |
|1991-1995 | |1991-1995 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
|Standard adjuvant therapy | |Standard adjuvant therapy | ||
− | | 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 |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa022794 Rodenhuis et al. 2003 (Dutch National Study)] |
|1993-1999 | |1993-1999 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Breast_cancer#FEC_2|FEC]] x 5 | |[[Breast_cancer#FEC_2|FEC]] x 5 | ||
| style="background-color:#d9ef8b" |Might have superior RFS | | style="background-color:#d9ef8b" |Might have superior RFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: This regimen is no longer used, but of historical interest.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup> | + | *[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup> IV |
− | *[[Thiotepa (Thioplex)]] 480 mg/m<sup>2</sup> | + | *[[Thiotepa (Thioplex)]] 480 mg/m<sup>2</sup> IV |
− | *[[Carboplatin (Paraplatin)]] 1600 mg/m<sup>2</sup> | + | *[[Carboplatin (Paraplatin)]] 1600 mg/m<sup>2</sup> IV |
− | + | ====Supportive therapy==== | |
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. [https://doi.org/10.1200/jco.1990.8.7.1239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2162912 PubMed] | + | # Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. [https://doi.org/10.1200/jco.1990.8.7.1239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2162912/ PubMed] |
− | # Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. [https:// | + | # Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. [https://doi.org/10.1016/S0140-6736(98)01350-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9716055/ PubMed] |
− | # Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https:// | + | # Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https://doi.org/10.1056/NEJM200004133421501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10760307/ PubMed] |
− | # Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. [https:// | + | # '''Dutch National Study:''' Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. [https://doi.org/10.1056/NEJMoa022794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12840087/ PubMed] [https://clinicaltrials.gov/study/NCT03087409 NCT03087409] |
==Cyclophosphamide, Etoposide, TBI {{#subobject:1fcca8|Regimen=1}}== | ==Cyclophosphamide, Etoposide, TBI {{#subobject:1fcca8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:a79295|Variant=1}}=== | ===Regimen {{#subobject:a79295|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/10.1200/jco.1998.16.1.48 Stiff et al. 1998] | |[https://doi.org/10.1200/jco.1998.16.1.48 Stiff et al. 1998] | ||
− | | style="background-color:#91cf61" |Phase | + | |1990-04 to 1994-11 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288718/ Thompson et al. 2008 (SWOG 9438)] | ||
+ | |1995-2004 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
<section begin=a79295 /> | <section begin=a79295 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cyclophosphamide (Cytoxan)]] 100 mg/kg IV over 1 to 2 hours once on day -2 | *[[Cyclophosphamide (Cytoxan)]] 100 mg/kg IV over 1 to 2 hours once on day -2 | ||
*[[Etoposide (Vepesid)]] 60 mg/kg IV over 4 hours once on day -4 | *[[Etoposide (Vepesid)]] 60 mg/kg IV over 4 hours once on day -4 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] with 150 cGy fractions given twice per day (fractions are at least 5 hours apart) x 8 fractions (total dose: 1200 cGy) over 4 days on days -8 to -5, with lung shielding for the final 60000 cGy |
**Note: Table 1 of Stiff et al. 1998 lists the dosage of each fraction as being 120 cGy, in contrast to the body text under "treatment regimen" saying each fraction is 150 cGy. It is believed that the 150 cGy dose is correct since 8 fractions of this results in the correct total dose of 1200 cGy. | **Note: Table 1 of Stiff et al. 1998 lists the dosage of each fraction as being 120 cGy, in contrast to the body text under "treatment regimen" saying each fraction is 150 cGy. It is believed that the 150 cGy dose is correct since 8 fractions of this results in the correct total dose of 1200 cGy. | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) once 2 hours prior to etoposide to prevent allergic reaction |
− | *[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) once 2 hours | + | *[[Hydrocortisone (Cortef)]] 100 mg (route not specified) once 2 hours prior to etoposide to prevent allergic reaction |
− | *[[Hydrocortisone (Cortef)]] 100 mg (route not specified) once 2 hours | ||
*"Continuous bladder irrigation and vigorous hydration were used" to protect against hemorrhagic cystitis | *"Continuous bladder irrigation and vigorous hydration were used" to protect against hemorrhagic cystitis | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=a79295 /> | <section end=a79295 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [https://doi.org/10.1200/jco.1998.16.1.48 link to original article] ''' | + | # Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [https://doi.org/10.1200/jco.1998.16.1.48 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9440722/ PubMed] |
+ | #'''SWOG 9438:''' Thompson JA, Fisher RI, Leblanc M, Forman SJ, Press OW, Unger JM, Nademanee AP, Stiff PJ, Petersdorf SH, Fefer A. Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438). Blood. 2008 Apr 15;111(8):4048-54. Epub 2008 Feb 6. [https://doi.org/10.1182/blood-2007-09-111708 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288718/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18256325/ PubMed] [https://clinicaltrials.gov/study/NCT00002649 NCT00002649] | ||
==Cyclophosphamide & TBI {{#subobject:0a4915|Regimen=1}}== | ==Cyclophosphamide & TBI {{#subobject:0a4915|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 | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a2b2d3|Variant=1}}=== | ===Regimen {{#subobject:a2b2d3|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/10.1056/NEJM198406143102403 Phillips et al. 1984] |
|1977-1982 | |1977-1982 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 954: | Line 1,182: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM198706113162402 Takvorian et al. 1987] |
|1982-1987 | |1982-1987 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
Line 962: | Line 1,190: | ||
|[https://doi.org/10.1200/JCO.2003.10.023 Schouten et al. 2003 (CUP)] | |[https://doi.org/10.1200/JCO.2003.10.023 Schouten et al. 2003 (CUP)] | ||
|1993-1997 | |1993-1997 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |CHOP x 3 | + | |[[#CHOP_888|CHOP]] x 3 |
| style="background-color:#d9ef8b" |Might have superior OS | | style="background-color:#d9ef8b" |Might have superior OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2004-10-3883 Dreyling et al. 2004] |
|1996-2004 | |1996-2004 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |Interferon alfa maintenance | + | |[[Mantle_cell_lymphoma#Interferon_alfa_monotherapy|Interferon alfa]] maintenance |
− | | style="background-color:#91cf60" |Seems to have superior PFS | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 7.5 vs 4.8 yrs<br>(HR 0.66, 95% CI 0.46-0.95) |
|- | |- | ||
|[https://doi.org/10.1038/sj.thj.6200359 Reimer et al. 2004] | |[https://doi.org/10.1038/sj.thj.6200359 Reimer et al. 2004] | ||
− | |2000- | + | |2000-2006 |
− | | style="background-color:#91cf61" | | + | | style="background-color:#91cf61" |Non-randomized |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update; note that this study was conducted in the pre-rituximab era.'' | ||
<section begin=a2b2d3 /> | <section begin=a2b2d3 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====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 days -3 & -2 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy) |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=a2b2d3 /> | <section end=a2b2d3 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. [https:// | + | # Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. [https://doi.org/10.1056/NEJM198406143102403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6374452/ PubMed] |
− | # Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. [https:// | + | # Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. [https://doi.org/10.1056/NEJM198706113162402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3295542/ PubMed] |
− | # '''CUP:''' Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. [https://doi.org/10.1200/JCO.2003.10.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14517188 PubMed] | + | # '''CUP:''' Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. [https://doi.org/10.1200/JCO.2003.10.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14517188/ PubMed] |
− | # Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. [https://doi.org/10.1038/sj.thj.6200359 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15297846 PubMed] | + | # Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. [https://doi.org/10.1038/sj.thj.6200359 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15297846/ PubMed] |
− | ## '''Update:''' Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. [https://doi.org/10.1200/jco.2008.17.4870 link to original article] ''' | + | ##'''Update:''' Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. [https://doi.org/10.1200/jco.2008.17.4870 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19029417/ PubMed] |
− | # Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. [ | + | # Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. [https://doi.org/10.1182/blood-2004-10-3883 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15591112/ PubMed] |
+ | ## '''Update:''' Zoellner AK, Unterhalt M, Stilgenbauer S, Hübel K, Thieblemont C, Metzner B, Topp M, Truemper L, Schmidt C, Bouabdallah K, Krauter J, Lenz G, Dürig J, Vergote V, Schäfer-Eckart K, André M, Kluin-Nelemans HC, van Hoof A, Klapper W, Hiddemann W, Dreyling M, Hoster E; European Mantle Cell Lymphoma Network. Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Sep;8(9):e648-e657. [https://doi.org/10.1016/s2352-3026(21)00195-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34450102/ PubMed] | ||
==Etoposide & TBI {{#subobject:9a9f4e|Regimen=1}}== | ==Etoposide & TBI {{#subobject:9a9f4e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Etoposide & TBI: Etoposide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | Etoposide & TBI: Etoposide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:1b94c5|Variant=1}}=== | ===Regimen {{#subobject:1b94c5|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://doi.org/10.1182/blood-2005-04-1623 Rowe et al. 2005 (MRC UKALL XII/ECOG E2993)] |
|1993-2003 | |1993-2003 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[Acute_lymphocytic_leukemia#International_ALL_Trial|International ALL Trial | + | |[[Acute_lymphocytic_leukemia#International_ALL_Trial|International ALL Trial]] consolidation, then [[Acute_lymphocytic_leukemia#POMP|POMP]] maintenance |
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
|- | |- | ||
Line 1,016: | Line 1,249: | ||
''Note: this is the same preparative regimen used for allogeneic 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 allogeneic transplant for certain patients; see reference for details. This regimen was evaluated in the treatment of acute lymphoblastic leukemia in CR1.'' | ||
<section begin=1b94c5 /> | <section begin=1b94c5 /> | ||
+ | <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)]] | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] 220 cGy twice per day in 6 fractions on days –6 to –4 (total dose: 1320 cGy) |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=1b94c5 /> | <section end=1b94c5 /> | ||
− | + | </div> | |
===References=== | ===References=== | ||
− | # '''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. [ | + | # '''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] |
− | ## '''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:''' 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:''' 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, 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, 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. [ | + | ## '''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] |
− | |||
==FEAM {{#subobject:0aac6f|Regimen=1}}== | ==FEAM {{#subobject:0aac6f|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FEAM: '''<u>F</u>'''otemustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | FEAM: '''<u>F</u>'''otemustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | ===Regimen {{#subobject:74d43c|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1 {{#subobject:74d43c|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://doi.org/10.1038/bmt.2009.318 Musso et al. 2009] | |[https://doi.org/10.1038/bmt.2009.318 Musso et al. 2009] | ||
− | | style="background-color:#91cf61" |Phase | + | |2007-2008 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053328/ Musso et al. 2015] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053328/ Musso et al. 2015] | ||
− | | style="background-color:#91cf61" | | + | |2007-2012 |
+ | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
<section begin=74d43c /> | <section begin=74d43c /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fotemustine (Muphoran)]] | + | *[[Fotemustine (Muphoran)]] 150 mg/m<sup>2</sup> IV once per day on days -7 & -6 (total dose: 300 mg/m<sup>2</sup>) |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) |
− | *[[Cytarabine (Ara-C)]] | + | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) |
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=74d43c /> | <section end=74d43c /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:74d84c|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/PMC5053328/ Musso et al. 2015] | ||
+ | |2007-2012 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |} | ||
+ | <section begin=74d84c /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fotemustine (Muphoran)]] 300 mg/m<sup>2</sup> IV once on day -6 | ||
+ | *[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) | ||
+ | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -5 to -2 (total dose: 1600 mg/m<sup>2</sup>) | ||
+ | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=74d84c /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. [https://doi.org/10.1038/bmt.2009.318 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19898504 PubMed] | + | # Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. [https://doi.org/10.1038/bmt.2009.318 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19898504/ PubMed] |
− | # Musso M, Messina G, Di Renzo N, Di Carlo P, Vitolo U, Scalone R, Marcacci G, Scalzulli PR, Moscato T, Matera R, Crescimanno A, Santarone S, Orciuolo E, Merenda A, Pavone V, Pastore D, Donnarumma D, Carella AM, Ciochetto C, Cascavilla N, Mele A, Lanza F, Di Nicola M, Bonizzoni E, Pinto A. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen. Br J Haematol. 2016 Jan;172(1):111-21. Epub 2015 Oct 12. [https:// | + | # Musso M, Messina G, Di Renzo N, Di Carlo P, Vitolo U, Scalone R, Marcacci G, Scalzulli PR, Moscato T, Matera R, Crescimanno A, Santarone S, Orciuolo E, Merenda A, Pavone V, Pastore D, Donnarumma D, Carella AM, Ciochetto C, Cascavilla N, Mele A, Lanza F, Di Nicola M, Bonizzoni E, Pinto A. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen. Br J Haematol. 2016 Jan;172(1):111-21. Epub 2015 Oct 12. [https://doi.org/10.1111/bjh.13803 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053328/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26458240/ PubMed] |
==LEED {{#subobject:ee43e6|Regimen=1}}== | ==LEED {{#subobject:ee43e6|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
LEED: '''<u>L</u>'''-PAM (Melphalan), '''<u>E</u>'''ndoxan (Cyclophosphamide), '''<u>E</u>'''toposide, '''<u>D</u>'''examethasone | LEED: '''<u>L</u>'''-PAM (Melphalan), '''<u>E</u>'''ndoxan (Cyclophosphamide), '''<u>E</u>'''toposide, '''<u>D</u>'''examethasone | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:47e3df|Variant=1}}=== | ===Regimen {{#subobject:47e3df|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/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)] | |[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)] | ||
− | | style="background-color:#91cf61" |Non-randomized | + | |2010-2013 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
''Note: this protocol does not appear to be commonly used outside of Japan.'' | ''Note: this protocol does not appear to be commonly used outside of Japan.'' | ||
<section begin=47e3df /> | <section begin=47e3df /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 130 mg/m<sup>2</sup> IV once on day -1 | *[[Melphalan (Alkeran)]] 130 mg/m<sup>2</sup> IV once on day -1 | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -4 & -3 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -4 & -3 | ||
*[[Etoposide (Vepesid)]] 500 mg/m<sup>2</sup> IV once per day on days -4 to -2 | *[[Etoposide (Vepesid)]] 500 mg/m<sup>2</sup> IV once per day on days -4 to -2 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days -4 to -1 | *[[Dexamethasone (Decadron)]] 40 mg IV once per day on days -4 to -1 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=47e3df /> | <section end=47e3df /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab | + | # '''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28029326/ PubMed] [https://clinicaltrials.gov/study/NCT01014208 NCT01014208] |
− | |||
==Melphalan & TBI {{#subobject:94f995|Regimen=1}}== | ==Melphalan & TBI {{#subobject:94f995|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Melphalan & TBI: Melphalan & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | Melphalan & TBI: Melphalan & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ad4db8|Variant=1}}=== | ===Regimen {{#subobject:ad4db8|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/10.3324/haematol.2009.011759 Gressin et al. 2010 (GOELAMS LM1996)] |
− | | style="background-color:#91cf61" |Phase | + | |1996-09 to 2000-12 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3324/haematol.2009.011759 Gressin et al. 2010 (GOELAMS LM2001)] |
− | | style="background-color:#91cf61" |Phase | + | |2003-09 to 2005-12 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
<section begin=ad4db8 /> | <section begin=ad4db8 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once (day not specified) | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once (day not specified) | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] : 800 cGy in 4 fractions (days not specified) | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] : 800 cGy in 4 fractions (days not specified) | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on unspecified day | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=ad4db8 /> | <section end=ad4db8 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''LM1996 | + | # '''GOELAMS LM1996:''' Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. [https://doi.org/10.3324/haematol.2009.011759 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913084/ link to PMC article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/20220059/ PubMed] |
+ | # '''GOELAMS LM2001:''' Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. [https://doi.org/10.3324/haematol.2009.011759 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913084/ link to PMC article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/20220059/ PubMed] [https://clinicaltrials.gov/study/NCT00285389 NCT00285389] | ||
==Melphalan monotherapy {{#subobject:404662|Regimen=1}}== | ==Melphalan monotherapy {{#subobject:404662|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:e63043|Variant=1}}=== | ===Regimen {{#subobject:e63043|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/10.7326/0003-4819-140-2-200401200-00008 Skinner et al. 2004] |
− | | style="background-color:#91cf61" | | + | | style="background-color:#91cf61" |Case series |
|- | |- | ||
|} | |} | ||
''Eligibility criteria: Biopsy-proven amyloid disease and at least 1 major organ involved, evidence of plasma cell dyscrasia, no heart failure or arrhythmia that cannot be medically managed, cardiac ejection fraction at least 40%, no pleural effusions, supine systolic blood pressure at least 90 mmHg, O2 saturation at least 95% on room air, lung diffusing capacity at least 50% predicted, SWOG performance status less than or equal to 2 unless due to neuropathy.'' | ''Eligibility criteria: Biopsy-proven amyloid disease and at least 1 major organ involved, evidence of plasma cell dyscrasia, no heart failure or arrhythmia that cannot be medically managed, cardiac ejection fraction at least 40%, no pleural effusions, supine systolic blood pressure at least 90 mmHg, O2 saturation at least 95% on room air, lung diffusing capacity at least 50% predicted, SWOG performance status less than or equal to 2 unless due to neuropathy.'' | ||
<section begin=e63043 /> | <section begin=e63043 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] by the following criteria: |
− | ** | + | **Younger than 65 years, cardiac ejection fraction at least 45%, and at least 2.5 x 10<sup>6</sup> CD34+ cells/kg collected: 100 mg/m<sup>2</sup> IV once per day on days 1 & 2 |
− | ** | + | **65 years or older or cardiac ejection fraction 40 to 44% or with 2 to 2.5 x 10<sup>6</sup> CD34+ cells/kg collected: 70 mg/m<sup>2</sup> IV once per day on days 1 & 2 |
− | + | ====Supportive therapy==== | |
− | + | *[[Autologous stem cells]] re-infused 24 to 72 hours after the last dose of melphalan | |
+ | '''One course''' | ||
+ | </div> | ||
<section end=e63043 /> | <section end=e63043 /> | ||
− | + | </div> | |
===References=== | ===References=== | ||
− | # Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. [ | + | # Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. [https://doi.org/10.1182/blood.V67.5.1298.1298 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3516252/ PubMed] |
− | # Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O'Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004 Jan 20;140(2):85-93. [ | + | # Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O'Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004 Jan 20;140(2):85-93. [https://doi.org/10.7326/0003-4819-140-2-200401200-00008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14734330/ PubMed] |
− | + | # Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP; IFM. Bortezomib, doxorubicin, cyclophosphamide, dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. [https://doi.org/10.1200/jco.2015.63.1929 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27114594/ PubMed] | |
− | # Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP; IFM. Bortezomib, doxorubicin, cyclophosphamide, dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. [https://doi.org/10.1200/jco.2015.63.1929 link to original article] ''' | ||
==R-BEAM {{#subobject:8b88db|Regimen=1}}== | ==R-BEAM {{#subobject:8b88db|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-BEAM: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | R-BEAM: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 500/300/1600/1600/140 {{#subobject:db487f|Variant=1}}=== | ===Regimen variant #1, 500/300/1600/1600/140 {{#subobject:db487f|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/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)] |
− | | style="background-color:#91cf61" |Non-randomized | + | |2008-2012 |
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | ''A minimum number of 2 | + | ''A minimum number of 2 x 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.'' |
<section begin=db487f /> | <section begin=db487f /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once on day -8 | *[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once on day -8 | ||
Line 1,165: | Line 1,443: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -6 to -3 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV once per day on days -6 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 | ||
− | + | ====Supportive therapy==== | |
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=db487f /> | <section end=db487f /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 750/300/800/800/140 {{#subobject:9131e1|Variant=1}}=== | ===Regimen variant #2, 750/300/800/800/140 {{#subobject:9131e1|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 1,177: | Line 1,460: | ||
|[https://doi.org/10.1200/JCO.2012.45.9453 Vose et al. 2013 (BMT CTN 0401)] | |[https://doi.org/10.1200/JCO.2012.45.9453 Vose et al. 2013 (BMT CTN 0401)] | ||
|2006-2009 | |2006-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |B-BEAM | + | |[[#B-BEAM_999|B-BEAM]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24 | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24 | ||
|- | |- | ||
|} | |} | ||
<section begin=9131e1 /> | <section begin=9131e1 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -19 & -12 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -19 & -12 | ||
Line 1,190: | Line 1,474: | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice 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 | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 | ||
− | + | ====Supportive therapy==== | |
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=9131e1 /> | <section end=9131e1 /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 750/300/1600/3200/140 {{#subobject:77f5a0|Variant=1}}=== | ===Regimen variant #3, 750/300/1600/3200/140 {{#subobject:77f5a0|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/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
− | ''A minimum number of 2 | + | ''A minimum number of 2 x 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.'' |
<section begin=77f5a0 /> | <section begin=77f5a0 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | ||
Line 1,210: | Line 1,500: | ||
*[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV twice per day on days -6 to -3 | *[[Cytarabine (Ara-C)]] 400 mg/m<sup>2</sup> IV twice per day on days -6 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 | ||
− | + | ====Supportive therapy==== | |
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=77f5a0 /> | <section end=77f5a0 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''BMT CTN 0401:''' Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. [https://doi.org/10.1200/JCO.2012.45.9453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635682/ link to PMC article] ''' | + | # '''BMT CTN 0401:''' Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. [https://doi.org/10.1200/JCO.2012.45.9453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635682/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23478060/ PubMed] [https://clinicaltrials.gov/study/NCT00329030 NCT00329030] |
− | # '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https:// | + | # '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25546611/ PubMed] [https://clinicaltrials.gov/study/NCT02099292 NCT02099292] |
− | + | # '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28953447/ PubMed] [https://clinicaltrials.gov/study/NCT00921414 NCT00921414] | |
− | # '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https:// | ||
− | |||
==R-TBI/Cy {{#subobject:9a5351|Regimen=1}}== | ==R-TBI/Cy {{#subobject:9a5351|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
R-TBI/Cy: '''<u>R</u>'''ituximab, '''<u>T</u>'''otal, '''<u>B</u>'''ody, '''<u>I</u>'''rradiation, '''<u>Cy</u>'''clophosphamide | R-TBI/Cy: '''<u>R</u>'''ituximab, '''<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:785614|Variant=1}}=== | ===Regimen {{#subobject:785614|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/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
− | ''A minimum number of 2 | + | ''A minimum number of 2 x 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.'' |
<section begin=785614 /> | <section begin=785614 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -8 & -2 | ||
Line 1,240: | Line 1,530: | ||
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day on days -3 & -2 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] with a total dose of 1200 cGy over 3 days (days -6 to -4) in fractions |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=785614 /> | <section end=785614 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https:// | + | # '''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25546611/ PubMed] [https://clinicaltrials.gov/study/NCT02099292 NCT02099292] |
− | |||
==TAM6 {{#subobject:c810fd|Regimen=1}}== | ==TAM6 {{#subobject:c810fd|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
TAM: '''<u>T</u>'''otal-body irradiation, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | TAM: '''<u>T</u>'''otal-body irradiation, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:4aee7c|Variant=1}}=== | ===Regimen {{#subobject:4aee7c|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-2011-09-370320 Delarue et al. 2012] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=4aee7c /> | <section begin=4aee7c /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] with a total dose of 1000 cGy over 3 days using twice per day fractions |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV every 12 hours for 2 days (total dose: 6000 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 1500 mg/m<sup>2</sup> IV every 12 hours for 2 days (total dose: 6000 mg/m<sup>2</sup>) | ||
*[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once | ||
− | ====Supportive | + | ====Supportive therapy==== |
− | "Antimicrobial prophylaxis and use of [[Filgrastim (Neupogen) | G-CSF]] or erythropoietin were permitted according to physician decision." | + | *[[Autologous stem cells]] re-infused on unspecified day |
+ | *"Antimicrobial prophylaxis and use of [[Filgrastim (Neupogen) | G-CSF]] or erythropoietin were permitted according to physician decision." | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=4aee7c /> | <section end=4aee7c /> | ||
+ | </div> | ||
+ | |||
===References=== | ===References=== | ||
− | # Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. [ | + | # Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. [https://doi.org/10.1182/blood-2011-09-370320 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22718839/ PubMed] |
− | |||
==TBI {{#subobject:1a2735|Regimen=1}}== | ==TBI {{#subobject:1a2735|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:635694|Variant=1}}=== | ===Regimen {{#subobject:635694|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/10.1056/NEJM195904022601401 McGovern et al. 1959] |
|1957-1958 | |1957-1958 | ||
| style="background-color:#ffffbe" |Pilot | | style="background-color:#ffffbe" |Pilot | ||
Line 1,294: | Line 1,587: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)] | ||
|1999-2007 | |1999-2007 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#R-CHOP|R-CHOP]] x 8 | |[[#R-CHOP|R-CHOP]] x 8 | ||
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior PFS24 (co-primary endpoint)<br>PFS24: 69% vs 55%<br>(HR 0.58, 95% CI 0.40-0.85)<br><br>Did not meet co-primary endpoint of OS24<br>OS24: 74% vs 71%<br>(HR 1.26, 95% CI 0.82-1.94) |
|- | |- | ||
|} | |} | ||
<section begin=635694 /> | <section begin=635694 /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] in | + | *[[External_beam_radiotherapy|Total body irradiation (TBI)]] in 150 cGy fractions twice per day on days -8 through -5 (total dose: 1200 cGy) |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=635694 /> | <section end=635694 /> | ||
− | + | </div> | |
+ | ===References=== | ||
+ | # McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. [https://doi.org/10.1056/NEJM195904022601401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13644566/ PubMed] | ||
+ | # '''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://doi.org/10.1056/NEJMoa1301077 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24171516/ PubMed] [https://clinicaltrials.gov/study/NCT00004031 NCT00004031] | ||
+ | ==TEAM {{#subobject:teace2|Regimen=1}}== | ||
+ | TEAM: '''<u>T</u>'''hiotepa, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d7btea|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/j.annonc.2023.10.095 Ladetto et al. 2023 (FIL FLAZ12)] | ||
+ | |2012-08 to 2019-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Follicular_lymphoma#Ibritumomab_tiuxetan_protocol_3|Zevalin]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | <section begin=d7t00a /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Thiotepa (Thioplex)]] 5 mg/kg IV every 12 hours on day -7 (total dose: 10 mg/kg) | ||
+ | *[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
+ | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV once per day on days -5 to -3 | ||
+ | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -2 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +2, continued until ANC greater than 1500/μL | ||
+ | '''One course''' | ||
+ | </div> | ||
+ | <section end=d7t00a /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | + | #'''FIL FLAZ12:''' Ladetto M, Tavarozzi R, Zanni M, Evangelista A, Ferrero S, Tucci A, Botto B, Bolis S, Volpetti S, Zilioli VR, Puccini B, Arcari A, Pavone V, Gaidano G, Corradini P, Tani M, Cavallo F, Milone G, Ghiggi C, Pinto A, Pastore D, Ferreri AJM, Latte G, Patti C, Re F, Benedetti F, Luminari S, Pennese E, Bossi E, Boccomini C, Anastasia A, Bottelli C, Ciccone G, Vitolo U. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial. Ann Oncol. 2024 Jan;35(1):118-129. Epub 2023 Nov 3. [https://doi.org/10.1016/j.annonc.2023.10.095 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37922989/ PubMed] [https://clinicaltrials.gov/study/NCT01827605 NCT01827605] | |
− | # ''' | ||
==V-BEAM {{#subobject:d6ea18|Regimen=1}}== | ==V-BEAM {{#subobject:d6ea18|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
V-BEAM: '''<u>V</u>'''elcade (Bortezomib), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | V-BEAM: '''<u>V</u>'''elcade (Bortezomib), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:7ef4f|Variant=1}}=== | ===Regimen {{#subobject:7ef4f|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/10.1016/j.bbmt.2014.01.004 William et al. 2014] |
− | | style="background-color:#91cf61" |Phase | + | |Not reported to 2009-08-14 |
+ | | style="background-color:#91cf61" |Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: the bortezomib dose is the modified MTD used in the phase 2 portion of the trial.'' |
<section begin=7ef4f /> | <section begin=7ef4f /> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Bortezomib (Velcade)]] on days -11, -8, -5, -2 | + | *[[Bortezomib (Velcade)]] 1 mg/m<sup>2</sup> (route not specified) once per day on days -11, -8, -5, -2 |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Carmustine (BCNU)]] | + | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -5 |
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV twice per day on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) |
− | *[[Cytarabine (Ara-C)]] | + | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days -5 to -2 (total dose: 800 mg/m<sup>2</sup>) |
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] 140 mg/m<sup>2</sup> IV once on day -1 |
+ | ====Supportive therapy==== | ||
+ | *[[Autologous stem cells]] re-infused on day 0 | ||
+ | '''One course''' | ||
+ | </div> | ||
<section end=7ef4f /> | <section end=7ef4f /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # William BM, Allen MS, Loberiza FR Jr, Bociek RG, Bierman PJ, Armitage JO, Vose JM. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma. Biol Blood Marrow Transplant. 2014 Apr;20(4):536-42. Epub 2014 Jan 14. [ | + | # William BM, Allen MS, Loberiza FR Jr, Bociek RG, Bierman PJ, Armitage JO, Vose JM. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma. Biol Blood Marrow Transplant. 2014 Apr;20(4):536-42. Epub 2014 Jan 14. [https://doi.org/10.1016/j.bbmt.2014.01.004 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24434781/ PubMed] |
==Z-BEAM {{#subobject:19f0d0|Regimen=1}}== | ==Z-BEAM {{#subobject:19f0d0|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Z-BEAM: '''<u>Z</u>'''evalin (Ibritumomab tiuxetan), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | Z-BEAM: '''<u>Z</u>'''evalin (Ibritumomab tiuxetan), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:9aeafe|Variant=1}}=== | ===Regimen variant #1 {{#subobject:9aeafe|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/10.1002/cncr.27418 Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)] |
− | | | + | |Not reported |
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
|[[#BEAM|BEAM]] | |[[#BEAM|BEAM]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint) |
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ Briones et al. 2013] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)] |
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 1,366: | Line 1,698: | ||
|} | |} | ||
<section begin=9aeafe /> | <section begin=9aeafe /> | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once on day -14, '''given first''' | *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once on day -14, '''given first''' | ||
+ | ====Radioconjugate therapy==== | ||
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, '''given second''' | *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, '''given second''' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 1,374: | Line 1,708: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -5 to -2 | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours 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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
− | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4 (Shimoni et al. 2012) or day +7 ( | + | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day +4 (Shimoni et al. 2012) or day +7 (GELTAMO Z-BEAM LDCGB) until engraftment |
*[[Valacyclovir (Valtrex)]] (dose not specified) for one month (Shimoni et al. 2012) | *[[Valacyclovir (Valtrex)]] (dose not specified) for one month (Shimoni et al. 2012) | ||
*[[Acyclovir (Zovirax)]] (dose not specified) for one month (Briones et al. 2013) | *[[Acyclovir (Zovirax)]] (dose not specified) for one month (Briones et al. 2013) | ||
− | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/frequency not specified) for six months (3 months in | + | *[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/frequency not specified) for six months (3 months in GELTAMO Z-BEAM LDCGB) |
− | ''' | + | '''One course''' |
+ | </div> | ||
<section end=9aeafe /> | <section end=9aeafe /> | ||
+ | </div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:e7f161|Variant=1}}=== | ===Regimen variant #2 {{#subobject:e7f161|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/10.1016/j.bbmt.2014.07.024 Fruchart et al. 2014 (ZBEAM2)] |
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
<section begin=e7f161 /> | <section begin=e7f161 /> | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Targeted therapy==== | ||
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days -21 & -14, '''given first on day -14''' | *[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days -21 & -14, '''given first on day -14''' | ||
− | *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, '''given second''' | + | ====Radioconjugate therapy==== |
− | ** | + | *[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] by the following laboratory-based criteria: |
+ | **Platelet count 150 x 10<sup>9</sup>/L or more: 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, '''given second''' | ||
+ | **Platelet count 100 up to 150 x 10<sup>9</sup>/L: 0.3 mCi/kg (maximum dose of 32 mCi) IV once on day -14, '''given second''' | ||
+ | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | *[[Carmustine (BCNU)]] 300 mg/m<sup>2</sup> IV once on day -7 | ||
Line 1,401: | Line 1,742: | ||
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -6 to -3 | *[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup> IV every 12 hours on days -6 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 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Autologous stem cells]] re-infused on day 0 |
*"According to standard use" | *"According to standard use" | ||
− | ''' | + | '''One course''' |
+ | </div> | ||
<section end=e7f161 /> | <section end=e7f161 /> | ||
+ | </div> | ||
===References=== | ===References=== | ||
− | # Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [ | + | # Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [https://doi.org/10.1016/j.exphem.2007.01.043 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17379063/ PubMed] |
− | # '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https:// | + | # '''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://doi.org/10.1002/cncr.27418 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22252613/ PubMed] [https://clinicaltrials.gov/study/NCT00491491 NCT00491491] |
− | # Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [ | + | # '''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [https://doi.org/10.3324/haematol.2013.093450 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24162789/ PubMed] EudraCT 2007-003198-22 |
− | # Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. | + | # '''ZBEAM2:''' Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. [https://doi.org/10.1016/j.bbmt.2014.07.024 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25072780/ PubMed] [https://clinicaltrials.gov/study/NCT00689169 NCT00689169] |
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[[Category:Autologous HSCT regimens]] | [[Category:Autologous HSCT regimens]] | ||
[[Category:Site-agnostic regimens]] | [[Category:Site-agnostic regimens]] |
Latest revision as of 17:14, 17 July 2024
Section editor | |
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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 autologous 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 autologous 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:
26 regimens on this page
54 variants on this page
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High dose therapy conditioning regimens, all lines of therapy
BCNU/TT
BCNU/TT: BCNU (Carmustine), ThioTepa
Regimen variant #1
Study | Evidence |
---|---|
Illerhaus et al. 2006 | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 400 mg/m2 IV once on day 50
- Thiotepa (Thioplex) 5 mg/kg (route not specified) once per day on days 51 & 52
Supportive therapy
- Autologous stem cells re-infused on day 56
- Granulocyte colony-stimulating factor starting on day 61, continued until WBC greater than 1 x 109/L for 3 days
- "Standard supportive measures were taken according to institutional guidelines."
One course
Regimen variant #2
Study | Evidence |
---|---|
Illerhaus et al. 2008 | Pilot, fewer than 20 pts |
Chemotherapy
- Carmustine (BCNU) 400 mg/m2 IV once on day 1
- Thiotepa (Thioplex) 5 mg/kg (route not specified) twice per day on days 2 & 3
Supportive therapy
- Autologous stem cells re-infused on day 7
One course
References
- Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. Epub 2006 Jul 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Illerhaus G, Müller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica. 2008 Jan;93(1):147-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
BEAC
BEAC: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Cyclophosphamide
Regimen variant #1
Study | Evidence |
---|---|
Geisler et al. 2008 (NLG MCL2) | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days 2 to 5
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days 2 to 5
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once per day on days 2 to 5
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Philip et al. 1995 (PARMA) | 1987-1994 | Phase 3 (E-esc) | DHAP x 4 | Seems to have superior OS |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV over 30 to 60 minutes once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 30 to 60 minutes twice per day on days 2 to 5
- Cytarabine (Ara-C) 100 mg/m2 IV over 30 minutes twice per day on days 2 to 5
- Cyclophosphamide (Cytoxan) 35 mg/kg IV over 60 minutes once per day on days 2 to 5
Supportive therapy
- Mesna (Mesnex) 8.3 mg/kg IV over 30 minutes every 4 hours on days 2 to 5 (optional)
- Autologous stem cells re-infused on day 7, given 48 hours after last dose of etoposide
One course
Regimen variant #3
Study | Evidence |
---|---|
Philip et al. 1991 (PARMA pilot) | Non-randomized |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV over 30 minutes once on day -13
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days -12 to -7
- Cytarabine (Ara-C) 100 mg/m2 IV twice per day on days -12 to -9
- Cyclophosphamide (Cytoxan) 35 mg/kg IV over 60 minutes once per day on days -12 to -9
Supportive therapy
- Mesna (Mesnex) 50 mg/kg IV once per day on days -12 to -9 (optional)
- Autologous stem cells re-infused on day 0
One course
References
- PARMA pilot: Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- PARMA: Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article dosing details in abstract have been reviewed by our editors PubMed
- NLG MCL2: Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
BEAM
BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1, 300/100q12/100q12/140 with 24-hour rest
Study | Evidence |
---|---|
Alvarnas et al. 2016 (BMT CTN 0803/AMC 071) | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, 300/100q12/100q12/140 with 48-hour rest
Study | Evidence |
---|---|
Van 't Veer et al. 2008 (HOVON 45) | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -6 to -3 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days -6 to -3 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #3, 300/100q12/200/140
Study | Dates of enrollment | Evidence |
---|---|---|
Philip et al. 1987 | 1980-1985 | Non-randomized |
Note: The manuscript did not specify which day peripheral blood stem cells were administered. This trial is of important historic interest because it indicated that patients with less than a partial response did worse than those with PR or better.
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes every 12 hours on days 2 to 5 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 200 mg/m2 IV once per day on days 2 to 5
- Melphalan (Alkeran) 140 mg/m2 IV over 5 minutes once on day 6
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Regimen variant #4, 300/100q12/200q12/140
Study | Evidence |
---|---|
Abrey et al. 2003 | Phase 2 |
Stewart et al. 2006 | Phase 2 |
d'Amore et al. 2012 (NLG-T-01) | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
- (described in some publications)
- Filgrastim (Neupogen) by the following weight-based criteria:
- Less than 70 kg: 300 mcg SC once per day, starting on day +7 after stem cell transplant
- More than 70 kg (reference did not clarify which dosage to use for patients who are exactly 70 kg): 480 mcg SC once per day, starting on day +7 after stem cell transplant
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Monday and Thursdays, until 6 months after BEAM
- Ciprofloxacin (Cipro) 500 mg PO twice per day while ANC less than 500/μL
- Antifungal prophylaxis with one of the following:
- Fluconazole (Diflucan) 100 mg PO once per day while ANC less than 500/μL
- Nystatin (Mycostatin) 500,000 units swish & swallow four times per day while ANC less than 500/μL
- Acyclovir (Zovirax) 400 mg PO three times per day while ANC less than 500/μL
One course
Regimen variant #5, 300/100q12/400/140
Study | Evidence |
---|---|
Geisler et al. 2008 (NLG MCL2) | Phase 2 |
Paper did not specify which day peripheral blood stem cells were administered.
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days 2 to 5 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days 2 to 5
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Regimen variant #6, 300/150q12/200q12/140
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Josting et al. 2005 | Not reported | Phase 2 | ||
Schmitz et al. 2002 (GHSG HD-R1) | 1993-1997 | Randomized (E-esc) | DexaBEAM | Seems to have superior FFTF |
Note: Josting et al. 2005 did not specify which day peripheral blood stem cells were administered.
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 150 mg/m2 IV every 12 hours on days -7 to -4 (total dose: 1200 mg/m2)
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -7 to -4 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -3
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #7, 300/200/100q12/140
Study | Dates of enrollment | Evidence |
---|---|---|
Colombat et al. 2006 | 1999-07 to 2001-11 | Phase 2 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day 1
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 2 to 5
- Cytarabine (Ara-C) 100 mg/m2 IV every 12 hours on days 2 to 5 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day 6
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
Regimen variant #8, 300/200/200/140
Study | Dates of enrollment | Evidence |
---|---|---|
Gisselbrecht et al. 2010 (CORAL) | 2003-2007 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 200 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #9, 300/200/200q12/140 with 24 hour rest
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL) | Not reported | Randomized Phase 2 (C) | Z-BEAM | Seems to have inferior OS |
Pardal et al. 2014 (GELTAMO-2006) | 2007-2009 | Phase 2 | ||
van Imhoff et al. 2016 (ORCHARRD) | 2010-2013 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -5 to -2 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
- Variously described:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4 "until engraftment"
- Valacyclovir (Valtrex) (dose not specified) for one month
- Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months
One course
Regimen variant #10, 300/200/200q12/140 with 48 hour rest
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmitz et al. 2021 (MYS-07-HMO-CTIL) | 2011-2014 | Phase 3 (C) | Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT | Did not meet primary endpoint of EFS36 |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -6 to -3
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -6 to -3 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #11, 300/200q12/200q12/140
Study | Evidence |
---|---|
Zinzani et al. 2003 | Retrospective |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 200 mg/m2 IV twice per day on days -6 to -3 (total dose: 1600 mg/m2)
- Cytarabine (Ara-C) 200 mg/m2 IV twice per day on days -6 to -3 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #12, 300/200/400/140
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ladetto et al. 2023 (FIL FLAZ12) | 2012-08 to 2019-09 | Phase 3 (C) | Zevalin | Did not meet primary endpoint of PFS |
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +2, continued until ANC greater than 1500/μL
One course
References
- Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GHSG HD-R1: Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Müller P, Kirchner H, Lohri A, Decker S, Koch B, Hasenclever D, Goldstone AH, Diehl V; German Hodgkin's Lymphoma Study Group; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15;359(9323):2065-71. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, De Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Guidice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Marchi E, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience. Leuk Lymphoma. 2004 Feb;45(2):321-6. PubMed
- Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article dosing details in abstract have been reviewed by our editors PubMed content property of HemOnc.org
- Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T; GOELAMS. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, Kim JW, Kim S, Huh J, Suh C. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008 Jan;87(1):43-8. Epub 2007 Aug 21. link to original article dosing details in abstract have been reviewed by our editors PubMed
- NLG MCL2: Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN87866680
- HOVON 45: Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CORAL: Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00137995
- SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00491491
- NLG-T-01: d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, Holte H, Österborg A, Merup M, Brown P, Kuittinen O, Erlanson M, Østenstad B, Fagerli UM, Gadeberg OV, Sundström C, Delabie J, Ralfkiaer E, Vornanen M, Toldbod HE. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012 Sep 1;30(25):3093-9. Epub 2012 Jul 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00791947
- GELTAMO-2006: Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01361191
- BMT CTN 0803/AMC 071: Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. Epub 2016 Jun 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01141712
- ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement dosing details in supplement have been reviewed by our editors PubMed NCT01014208
- MYS-07-HMO-CTIL: Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00984412
- FIL FLAZ12: Ladetto M, Tavarozzi R, Zanni M, Evangelista A, Ferrero S, Tucci A, Botto B, Bolis S, Volpetti S, Zilioli VR, Puccini B, Arcari A, Pavone V, Gaidano G, Corradini P, Tani M, Cavallo F, Milone G, Ghiggi C, Pinto A, Pastore D, Ferreri AJM, Latte G, Patti C, Re F, Benedetti F, Luminari S, Pennese E, Bossi E, Boccomini C, Anastasia A, Bottelli C, Ciccone G, Vitolo U. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial. Ann Oncol. 2024 Jan;35(1):118-129. Epub 2023 Nov 3. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01827605
BeEAM
BeEAM: Bendamustine, Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Visani et al. 2011 | 2008-08 to 2010-06 | Phase 1/2 |
Chemotherapy
- Bendamustine 200 mg/m2 IV once per day on days -7 & -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed EudraCT 2008-002736-15
Bortezomib & Melphalan
Bor-HDM: Bortezomib, High Dose Melphalan
Regimen variant #1, HDM 140 mg/m2
Study | Evidence |
---|---|
Sanchorawala et al. 2015 (X05292) | Phase 2 |
Targeted therapy
- Bortezomib (Velcade) 1 mg/m2 IV once per day on days -6, -3, +1, +4
Chemotherapy
- Melphalan (Alkeran) 70 mg/m2 IV once per day on days -2 & -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, HDM 200 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Roussel et al. 2009 | 2007-07 to 2007-12 | Phase 2 |
Sanchorawala et al. 2015 (X05292) | 2010-01 to 2013-08 | Phase 2 |
Targeted therapy
- Bortezomib (Velcade) 1 mg/m2 IV once per day on days -6, -3, +1, +4
Chemotherapy
- Melphalan (Alkeran) 100 mg/m2 IV once per day on days -2 & -1
- Roussel et al. 2009 gave as a single 200 mg/m2 dose on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D, Hulin C, Fruchart C, Marit G, Pégourié B, Lenain P, Araujo C, Kolb B, Randriamalala E, Royer B, Stoppa AM, Dib M, Dorvaux V, Garderet L, Mathiot C, Avet-Loiseau H, Harousseau JL, Attal M; Intergroupe Francophone du Myélome. Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood. 2010 Jan 7;115(1):32-7. Epub 2009 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00642395
- X05292: Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain amyloidosis: Results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015 Aug;21(8):1445-51. Epub 2015 Apr 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01083316
Busulfan & Cyclophosphamide
BuCy: Busulfan & Cyclophosphamide
Regimen variant #1, 12.8/120
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Liu et al. 2023 | 2016-01 to 2019-02 | Phase 3 (C) | Ida-BuCy | Did not meet primary endpoint of RR |
Chemotherapy
- Busulfan (Myleran) 3.2 mg/kg/day (route/frequency not specified) on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, 16/120
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vellenga et al. 2011 (HOVON-SAKK AML-29/AML-42) | 1995-2006 | Phase 3 (E-esc) | Etoposide & Mitoxantrone | Might have superior RFS (primary endpoint) |
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO (frequency not specified) on days -7 to -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #3, 16/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ravindranath et al. 1996 | 1988-1993 | Phase 3 (E-esc) | Intensive chemotherapy | Did not meet primary endpoint of EFS24 |
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -9 to -6
- Cyclophosphamide (Cytoxan) 50 mg/kg IV once per day on days -5 to -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ; Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996 May 30;334(22):1428-34. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- HOVON-SAKK AML-29/AML-42: Vellenga E, van Putten W, Ossenkoppele GJ, Verdonck LF, Theobald M, Cornelissen JJ, Huijgens PC, Maertens J, Gratwohl A, Schaafsma R, Schanz U, Graux C, Schouten HC, Ferrant A, Bargetzi M, Fey MF, Löwenberg B; Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research. Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood. 2011 Dec 1;118(23):6037-42. Epub 2011 Sep 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Liu H, Huang F, Zhang Y, Wu M, Xu N, Fan Z, Sun Z, Li X, Lin D, Xiong Y, Liu X, Lin R, Shi P, Xu J, Wang Z, Li X, Sun J, Liu Q, Xuan L. Idarubicin plus BuCy versus BuCy conditioning regimens for intermediate-risk acute myeloid leukemia in first complete remission undergoing auto-HSCT: An open-label, multicenter, randomized phase 3 trial. Am J Hematol. 2023 Mar;98(3):408-412. Epub 2023 Jan 1. link to original article PubMed NCT02671708
Busulfan & Melphalan
BuMel: Busulfan & Melphalan
Regimen variant #1, PO busulfan (12 mg/kg)
Study | Evidence |
---|---|
Yanada et al. 2013 (JALSG APL205R) | Phase 2 |
This regimen was evaluated in the setting of relapsed acute promyelocytic leukemia.
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -6 to -4 (total dose of 12 mg/kg)
- Melphalan (Alkeran) 70 mg/m2 IV bolus once per day on days -3 & -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, PO busulfan (16 mg/kg), mel 140 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Atra et al. 1997 | Not reported | Phase 2, fewer than 20 pts | ||
Whelan et al. 2018 (R2Loc) | 2000-2015 | Phase 3 (E-esc) | VAI | Seems to have superior OS (secondary endpoint) |
This regimen was evaluated in the setting of poor risk Ewing sarcoma.
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #3, PO busulfan (16 mg/kg), mel 160 mg/m2
Study | Dates of enrollment | Evidence |
---|---|---|
Atra et al. 1997 | Not reported | Phase 2, fewer than 20 pts |
This regimen was evaluated in the setting of poor risk Ewing sarcoma.
Chemotherapy
- Busulfan (Myleran) 1 mg/kg PO every 6 hours on days -5 to -2 (total dose of 16 mg/kg)
- Melphalan (Alkeran) 160 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #4, IV busulfan
Study | Dates of enrollment | Evidence |
---|---|---|
Strauss et al. 2003 | 1998-01 to 1999-06 | Phase 2 |
This regimen was evaluated in the setting of metastatic Ewing sarcoma. Note that melphalan is reported as given on day 2 (not day -2) in the original reference but this is surely an error.
Chemotherapy
- Busulfan (Myleran) 150 mg/m2 IV once per day on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Atra A, Whelan JS, Calvagna V, Shankar AG, Ashley S, Shepherd V, Souhami RL, Pinkerton CR. High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma. Bone Marrow Transplant. 1997 Nov;20(10):843-6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Strauss SJ, McTiernan A, Driver D, Hall-Craggs M, Sandison A, Cassoni AM, Kilby A, Michelagnoli M, Pringle J, Cobb J, Briggs T, Cannon S, Witt J, Whelan JS. Single center experience of a new intensive induction therapy for Ewing's family of tumors: feasibility, toxicity, and stem cell mobilization properties. J Clin Oncol. 2003 Aug 1;21(15):2974-81. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- JALSG APL205R: Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01908621
- R2Loc: Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Juergens H, Oberlin O; Euro-EWING-99 and EWING-2008 Investigators. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-EWING99 and Ewing-2008. J Clin Oncol. 2018 Nov 1;36(31):3110-9. Epub 2018 Sep 6. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00020566
Bu/TT
Bu/TT: Busulfan, ThioTepa
Regimen
Study | Evidence |
---|---|
Montemurro et al. 2007 (OSHO-53) | Phase 2 |
Chemotherapy
- Busulfan (Myleran) 4 mg/kg PO four times per day on days -8 to -5
- Thiotepa (Thioplex) 5 mg/kg IV once per day on days -4 & -3
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- OSHO-53: Montemurro M, Kiefer T, Schüler F, Al-Ali HK, Wolf HH, Herbst R, Haas A, Helke K, Theilig A, Lotze C, Hirt C, Niederwieser D, Schwenke M, Krüger WH, Dölken G. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007 Apr;18(4):665-71. Epub 2006 Dec 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Bu/TT/Cy
Bu/TT/Cy: Busulfan, ThioTepa, Cyclophosphamide
TBC: Thiotepa, Busulfan, , Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Omuro et al. 2015 (MSK 04-129) | Phase 2 |
Primary indication: primary CNS lymphoma (PCNSL)
Chemotherapy
- Thiotepa (Thioplex) 250 mg/m2 IV once per day on days -9, -8, and -7
- Busulfan (Myleran) 3.2 mg/kg IV once per day on days -6, -5, and -4
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 and -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- MSK 04-129: Omuro A, Correa DD, DeAngelis LM, Moskowitz CH, Matasar MJ, Kaley TJ, Gavrilovic IT, Nolan C, Pentsova E, Grommes CC, Panageas KS, Baser RE, Faivre G, Abrey LE, Sauter CS. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015 Feb 26;125(9):1403-10. Epub 2015 Jan 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00596154
- Retrospective: DeFilipp Z, Li S, El-Jawahri A, Armand P, Nayak L, Wang N, Batchelor TT, Chen YB. High-dose chemotherapy with thiotepa, busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017 Aug 15;123(16):3073-3079. Epub 2017 Apr 3. link to original article PubMed
CBV
CBV: Cyclophosphamide, BiCNU (Carmustine), VP-16 (Etoposide)
Regimen variant #1, 100/300/60, some BSA-based
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stiff et al. 2013 (SWOG S9704) | 1999-2007 | Phase 3 (E-esc) | R-CHOP x 8 | Superior PFS24 (co-primary endpoint) PFS24: 69% vs 55% (HR 0.58, 95% CI 0.40-0.85) Did not meet co-primary endpoint of OS24 OS24: 74% vs 71% (HR 1.26, 95% CI 0.82-1.94) |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/kg (IBW) IV once on day -2
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 60 mg/kg (IBW) IV once on day -4
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, 100/15/60, all weight-based
Study | Dates of enrollment | Evidence |
---|---|---|
Stiff et al. 1998 | 1990-1994 | Phase 2 |
Damon et al. 2009 (CALGB 59909) | 2001-2004 | Phase 2 |
Note: Stiff et al. 1998 based BCNU dosing on ideal body weight, whereas CALGB 59909 capped based on BSA, as described below.
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/kg IV over 2 hours once on day -2
- Carmustine (BCNU) 15 mg/kg (maximum dose of 550 mg/m2) IV over 60 minutes once on day -6
- Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
Supportive therapy
- Autologous stem cells re-infused on day 0
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4, to continue until ANC greater than 5000/μL once or greater than 1500/μL twice
- Levofloxacin (Levaquin) 500 mg PO once per day, starting on day +2, to continue until ANC at least 500/μL
- Fluconazole (Diflucan) 200 mg PO once per day, starting on day +1, to continue until ANC at least 500/μL
- Acyclovir (Zovirax) 200 mg PO three times per day, starting on day -2, to continue until 1 year after HSCT
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day on Saturday and Sunday, to continue until 3 months after HSCT
Additional considerations
If any patient appeared to be experiencing carmustine-induced pneumonitis:
- Prednisone (Sterapred) 0.5 mg/kg PO twice per day x 2 weeks, then tapered over 4 weeks
One course
Regimen variant #3, 1500/300/250, all BSA-based
Study | Evidence |
---|---|
Zinzani et al. 2003 | Retrospective |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once per day on days -6 to -3
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 250 mg/m2 IV once per day on days -6 to -4
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #4, 1800/600/400
Study | Dates of enrollment | Evidence |
---|---|---|
Reece et al. 1994 | 1985-1988 | Phase 2, fewer than 20 pts |
Note: the lower of IBW or ABW was used in the dosing calculations.
Chemotherapy
- Cyclophosphamide (Cytoxan) 1800 mg/m2 IV over 2 hours once per day on days -7 to -4
- Carmustine (BCNU) 600 mg/m2 IV once on day -3
- Etoposide (Vepesid) 400 mg/m2 IV over 60 minutes every 12 hours on days -7 to -5
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Reece DE, Connors JM, Spinelli JJ, Barnett MJ, Fairey RN, Klingemann HG, Nantel SH, O'Reilly S, Shepherd JD, Sutherland HJ, Voss N, Chan KW, Phillips GL. Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy. Blood. 1994 Mar 1;83(5):1193-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; SWOG. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Zinzani PL, Tani M, Gabriele A, Gherlinzoni F, de Vivo A, Ricci P, Bandini G, Lemoli RM, Motta MR, Rizzi S, Giudice V, Zompatori M, Stefoni V, Alinari L, Musuraca G, Bassi S, Conte R, Pileri S, Tura S, Baccarani M. High-dose therapy with autologous transplantation for Hodgkin's disease: the Bologna experience. Haematologica. 2003 May;88(5):522-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CALGB 59909: Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00020943
- SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00004031
CBV-Mx
CBV-Mx: Cyclophosphamide, BiCNU (Carmustine), VP-16 (Etoposide), Mitoxantrone
CBVM: Cyclophosphamide, BiCNU (Carmustine), VP-16 (Etoposide), Mitoxantrone
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Morschhauser et al. 2008 (GELA/SFGM H96) | 1995-01 to 2002-12 | Phase 2 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2/day IV on days -7 to -4
- Carmustine (BCNU) 300 mg/m2 IV once on day -4
- Etoposide (Vepesid) 250 mg/m2/day IV on days -7 to -4
- Mitoxantrone (Novantrone) 30 mg/m2 IV once on day -8
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Haioun et al. 2009 (LNH 98-3) | 1999-2004 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1500 mg/m2/day IV on days 2 to 5
- Carmustine (BCNU) 300 mg/m2 IV once on day 6
- Etoposide (Vepesid) 250 mg/m2/day IV on days 2 to 5
- Mitoxantrone (Novantrone) 45 mg/m2 IV once on day 1
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
References
- GELA/SFGM H96: Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA; SFGM. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. link to original article link to PMC article PubMed
- LNH 98-3: Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00169169
CHUT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Biron et al. 2007 (Pegase 03) | 1995-2001 | Phase 3 (E-esc) | No further treatment | Superior DFS |
Note: This regimen is no longer used, but of historical interest.
Chemotherapy
- Cyclophosphamide (Cytoxan) 6000 mg/m2
- Thiotepa (Thioplex) 800 mg/m2
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
References
- Pegase 03: Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. link to original article PubMed NCT00002870
CTCb
CTCb: Cyclophosphamide, Thiotepa, Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eder et al. 1990 | 1987-1988 | Phase 1/2 | ||
Stadtmauer et al. 2000 | 1990-1997 | Phase 3 (E-esc) | CMF | Did not meet primary endpoint of OS |
Rodenhuis et al. 1998 | 1991-1995 | Randomized Phase 2 (E-esc) | Standard adjuvant therapy | Did not meet co-primary endpoints of DFS/OS |
Rodenhuis et al. 2003 (Dutch National Study) | 1993-1999 | Phase 3 (E-esc) | FEC x 5 | Might have superior RFS |
Note: This regimen is no longer used, but of historical interest.
Chemotherapy
- Cyclophosphamide (Cytoxan) 6000 mg/m2 IV
- Thiotepa (Thioplex) 480 mg/m2 IV
- Carboplatin (Paraplatin) 1600 mg/m2 IV
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
References
- Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. link to original article PubMed
- Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. link to original article PubMed
- Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed
- Dutch National Study: Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. link to original article PubMed NCT03087409
Cyclophosphamide, Etoposide, TBI
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Stiff et al. 1998 | 1990-04 to 1994-11 | Phase 2 |
Thompson et al. 2008 (SWOG 9438) | 1995-2004 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/kg IV over 1 to 2 hours once on day -2
- Etoposide (Vepesid) 60 mg/kg IV over 4 hours once on day -4
Radiotherapy
- Total body irradiation (TBI) with 150 cGy fractions given twice per day (fractions are at least 5 hours apart) x 8 fractions (total dose: 1200 cGy) over 4 days on days -8 to -5, with lung shielding for the final 60000 cGy
- Note: Table 1 of Stiff et al. 1998 lists the dosage of each fraction as being 120 cGy, in contrast to the body text under "treatment regimen" saying each fraction is 150 cGy. It is believed that the 150 cGy dose is correct since 8 fractions of this results in the correct total dose of 1200 cGy.
Supportive therapy
- Diphenhydramine (Benadryl) 25 mg (route not specified) once 2 hours prior to etoposide to prevent allergic reaction
- Hydrocortisone (Cortef) 100 mg (route not specified) once 2 hours prior to etoposide to prevent allergic reaction
- "Continuous bladder irrigation and vigorous hydration were used" to protect against hemorrhagic cystitis
- Autologous stem cells re-infused on day 0
One course
References
- Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; SWOG. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SWOG 9438: Thompson JA, Fisher RI, Leblanc M, Forman SJ, Press OW, Unger JM, Nademanee AP, Stiff PJ, Petersdorf SH, Fefer A. Total body irradiation, etoposide, cyclophosphamide, and autologous peripheral blood stem-cell transplantation followed by randomization to therapy with interleukin-2 versus observation for patients with non-Hodgkin lymphoma: results of a phase 3 randomized trial by the Southwest Oncology Group (SWOG 9438). Blood. 2008 Apr 15;111(8):4048-54. Epub 2008 Feb 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00002649
Cyclophosphamide & TBI
Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Phillips et al. 1984 | 1977-1982 | Non-randomized | ||
Takvorian et al. 1987 | 1982-1987 | Non-randomized | ||
Schouten et al. 2003 (CUP) | 1993-1997 | Phase 3 (E-esc) | CHOP x 3 | Might have superior OS |
Dreyling et al. 2004 | 1996-2004 | Phase 3 (E-esc) | Interferon alfa maintenance | Seems to have superior PFS (primary endpoint) Seems to have superior OS1 (secondary endpoint) Median OS: 7.5 vs 4.8 yrs (HR 0.66, 95% CI 0.46-0.95) |
Reimer et al. 2004 | 2000-2006 | Non-randomized |
1Reported efficacy is based on the 2021 update; note that this study was conducted in the pre-rituximab era.
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. link to original article PubMed
- Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. link to original article PubMed
- CUP: Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. link to original article PubMed
- Reimer P, Schertlin T, Rüdiger T, Geissinger E, Roth S, Kunzmann V, Weissinger F, Nerl C, Schmitz N, Müller-Hermelink HK, Wilhelm M. Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J. 2004;5(4):304-11. link to original article PubMed
- Update: Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, Engert A, Einsele H, Müller-Hermelink HK, Wilhelm M. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009 Jan 1;27(1):106-13. Epub 2008 Nov 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. link to original article PubMed
- Update: Zoellner AK, Unterhalt M, Stilgenbauer S, Hübel K, Thieblemont C, Metzner B, Topp M, Truemper L, Schmidt C, Bouabdallah K, Krauter J, Lenz G, Dürig J, Vergote V, Schäfer-Eckart K, André M, Kluin-Nelemans HC, van Hoof A, Klapper W, Hiddemann W, Dreyling M, Hoster E; European Mantle Cell Lymphoma Network. Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Sep;8(9):e648-e657. link to original article PubMed
Etoposide & TBI
Etoposide & TBI: Etoposide & Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) | 1993-2003 | Phase 3 (E-esc) | International ALL Trial consolidation, then POMP maintenance | Seems to have inferior OS |
Note: this is the same preparative regimen used for allogeneic 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)
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- 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
FEAM
FEAM: Fotemustine, Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1
Study | Dates of enrollment | Evidence |
---|---|---|
Musso et al. 2009 | 2007-2008 | Phase 2 |
Musso et al. 2015 | 2007-2012 | Non-randomized |
Chemotherapy
- Fotemustine (Muphoran) 150 mg/m2 IV once per day on days -7 & -6 (total dose: 300 mg/m2)
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days -5 to -2 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Musso et al. 2015 | 2007-2012 | Non-randomized |
Chemotherapy
- Fotemustine (Muphoran) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days -5 to -2 (total dose: 1600 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Musso M, Messina G, Di Renzo N, Di Carlo P, Vitolo U, Scalone R, Marcacci G, Scalzulli PR, Moscato T, Matera R, Crescimanno A, Santarone S, Orciuolo E, Merenda A, Pavone V, Pastore D, Donnarumma D, Carella AM, Ciochetto C, Cascavilla N, Mele A, Lanza F, Di Nicola M, Bonizzoni E, Pinto A. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen. Br J Haematol. 2016 Jan;172(1):111-21. Epub 2015 Oct 12. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
LEED
LEED: L-PAM (Melphalan), Endoxan (Cyclophosphamide), Etoposide, Dexamethasone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
van Imhoff et al. 2016 (ORCHARRD) | 2010-2013 | Non-randomized part of phase 3 RCT |
Note: this protocol does not appear to be commonly used outside of Japan.
Chemotherapy
- Melphalan (Alkeran) 130 mg/m2 IV once on day -1
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -4 & -3
- Etoposide (Vepesid) 500 mg/m2 IV once per day on days -4 to -2
Glucocorticoid therapy
- Dexamethasone (Decadron) 40 mg IV once per day on days -4 to -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- ORCHARRD: van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. link to original article link to data supplement dosing details in supplement have been reviewed by our editors PubMed NCT01014208
Melphalan & TBI
Melphalan & TBI: Melphalan & Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gressin et al. 2010 (GOELAMS LM1996) | 1996-09 to 2000-12 | Phase 2 |
Gressin et al. 2010 (GOELAMS LM2001) | 2003-09 to 2005-12 | Phase 2 |
Chemotherapy
- Melphalan (Alkeran) 140 mg/m2 IV once (day not specified)
Radiotherapy
- Total body irradiation (TBI) : 800 cGy in 4 fractions (days not specified)
Supportive therapy
- Autologous stem cells re-infused on unspecified day
One course
References
- GOELAMS LM1996: Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. link to original article link to PMC article contains partial protocol PubMed
- GOELAMS LM2001: Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. link to original article link to PMC article contains partial protocol PubMed NCT00285389
Melphalan monotherapy
Regimen
Study | Evidence |
---|---|
Skinner et al. 2004 | Case series |
Eligibility criteria: Biopsy-proven amyloid disease and at least 1 major organ involved, evidence of plasma cell dyscrasia, no heart failure or arrhythmia that cannot be medically managed, cardiac ejection fraction at least 40%, no pleural effusions, supine systolic blood pressure at least 90 mmHg, O2 saturation at least 95% on room air, lung diffusing capacity at least 50% predicted, SWOG performance status less than or equal to 2 unless due to neuropathy.
Chemotherapy
- Melphalan (Alkeran) by the following criteria:
- Younger than 65 years, cardiac ejection fraction at least 45%, and at least 2.5 x 106 CD34+ cells/kg collected: 100 mg/m2 IV once per day on days 1 & 2
- 65 years or older or cardiac ejection fraction 40 to 44% or with 2 to 2.5 x 106 CD34+ cells/kg collected: 70 mg/m2 IV once per day on days 1 & 2
Supportive therapy
- Autologous stem cells re-infused 24 to 72 hours after the last dose of melphalan
One course
References
- Barlogie B, Hall R, Zander A, Dicke K, Alexanian R. High-dose melphalan with autologous bone marrow transplantation for multiple myeloma. Blood. 1986 May;67(5):1298-301. link to original article PubMed
- Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O'Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med. 2004 Jan 20;140(2):85-93. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP; IFM. Bortezomib, doxorubicin, cyclophosphamide, dexamethasone induction followed by stem cell transplantation for primary plasma cell leukemia: a prospective phase II study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article dosing details in abstract have been reviewed by our editors PubMed
R-BEAM
R-BEAM: Rituximab, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1, 500/300/1600/1600/140
Study | Dates of enrollment | Evidence |
---|---|---|
Le Gouill et al. 2017 (LyMa) | 2008-2012 | Non-randomized part of phase 3 RCT |
A minimum number of 2 x 106/kg bw CD34-positive cells were required to proceed.
Targeted therapy
- Rituximab (Rituxan) 500 mg/m2 IV once on day -8
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 400 mg/m2 IV once per day on days -6 to -3
- Cytarabine (Ara-C) 400 mg/m2 IV once per day on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #2, 750/300/800/800/140
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vose et al. 2013 (BMT CTN 0401) | 2006-2009 | Phase 3 (C) | B-BEAM | Did not meet primary endpoint of PFS24 |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -19 & -12
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 100 mg/m2 IV twice 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
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
Regimen variant #3, 750/300/1600/3200/140
Study | Evidence |
---|---|
Kirschey et al. 2014 (Mz-135) | Phase 2 |
A minimum number of 2 x 106/kg bw CD34-positive cells were required to proceed.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -8 & -2
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 200 mg/m2 IV twice per day on days -6 to -3
- Cytarabine (Ara-C) 400 mg/m2 IV twice per day on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- BMT CTN 0401: Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00329030
- Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02099292
- LyMa: Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. link to original article link to protocol dosing details in supplement have been reviewed by our editors PubMed NCT00921414
R-TBI/Cy
R-TBI/Cy: Rituximab, Total, Body, Irradiation, Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Kirschey et al. 2014 (Mz-135) | Phase 2 |
A minimum number of 2 x 106/kg bw CD34-positive cells were required to proceed.
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days -8 & -2
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation (TBI) with a total dose of 1200 cGy over 3 days (days -6 to -4) in fractions
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- Mz-135: Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02099292
TAM6
TAM: Total-body irradiation, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
---|---|
Delarue et al. 2012 | Phase 2 |
Radiotherapy
- Total body irradiation (TBI) with a total dose of 1000 cGy over 3 days using twice per day fractions
Chemotherapy
- Cytarabine (Ara-C) 1500 mg/m2 IV every 12 hours for 2 days (total dose: 6000 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once
Supportive therapy
- Autologous stem cells re-infused on unspecified day
- "Antimicrobial prophylaxis and use of G-CSF or erythropoietin were permitted according to physician decision."
One course
References
- Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed
TBI
TBI: Total Body Irradiation
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McGovern et al. 1959 | 1957-1958 | Pilot | ||
Stiff et al. 2013 (SWOG S9704) | 1999-2007 | Phase 3 (E-esc) | R-CHOP x 8 | Superior PFS24 (co-primary endpoint) PFS24: 69% vs 55% (HR 0.58, 95% CI 0.40-0.85) Did not meet co-primary endpoint of OS24 OS24: 74% vs 71% (HR 1.26, 95% CI 0.82-1.94) |
Radiotherapy
- Total body irradiation (TBI) in 150 cGy fractions twice per day on days -8 through -5 (total dose: 1200 cGy)
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. link to original article PubMed
- SWOG S9704: Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00004031
TEAM
TEAM: Thiotepa, Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ladetto et al. 2023 (FIL FLAZ12) | 2012-08 to 2019-09 | Phase 3 (C) | Zevalin | Did not meet primary endpoint of PFS |
Chemotherapy
- Thiotepa (Thioplex) 5 mg/kg IV every 12 hours on day -7 (total dose: 10 mg/kg)
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -3
- Cytarabine (Ara-C) 200 mg/m2 IV once per day on days -5 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +2, continued until ANC greater than 1500/μL
One course
References
- FIL FLAZ12: Ladetto M, Tavarozzi R, Zanni M, Evangelista A, Ferrero S, Tucci A, Botto B, Bolis S, Volpetti S, Zilioli VR, Puccini B, Arcari A, Pavone V, Gaidano G, Corradini P, Tani M, Cavallo F, Milone G, Ghiggi C, Pinto A, Pastore D, Ferreri AJM, Latte G, Patti C, Re F, Benedetti F, Luminari S, Pennese E, Bossi E, Boccomini C, Anastasia A, Bottelli C, Ciccone G, Vitolo U. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial. Ann Oncol. 2024 Jan;35(1):118-129. Epub 2023 Nov 3. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01827605
V-BEAM
V-BEAM: Velcade (Bortezomib), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
William et al. 2014 | Not reported to 2009-08-14 | Phase 1/2 |
Note: the bortezomib dose is the modified MTD used in the phase 2 portion of the trial.
Targeted therapy
- Bortezomib (Velcade) 1 mg/m2 (route not specified) once per day on days -11, -8, -5, -2
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -5
- Etoposide (Vepesid) 100 mg/m2 IV twice per day on days -5 to -2 (total dose: 800 mg/m2)
- Cytarabine (Ara-C) 100 mg/m2 IV twice per day on days -5 to -2 (total dose: 800 mg/m2)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
One course
References
- William BM, Allen MS, Loberiza FR Jr, Bociek RG, Bierman PJ, Armitage JO, Vose JM. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma. Biol Blood Marrow Transplant. 2014 Apr;20(4):536-42. Epub 2014 Jan 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Z-BEAM
Z-BEAM: Zevalin (Ibritumomab tiuxetan), BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL) | Not reported | Randomized Phase 2 (E-esc) | BEAM | Seems to have superior OS (secondary endpoint) |
Briones et al. 2013 (GELTAMO Z-BEAM LDCGB) | 2008-2010 | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 250 mg/m2 IV once on day -14, given first
Radioconjugate therapy
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -6
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days -5 to -2
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -5 to -2
- Melphalan (Alkeran) 140 mg/m2 IV once on day -1
Supportive therapy
- Autologous stem cells re-infused on day 0
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day +4 (Shimoni et al. 2012) or day +7 (GELTAMO Z-BEAM LDCGB) until engraftment
- Valacyclovir (Valtrex) (dose not specified) for one month (Shimoni et al. 2012)
- Acyclovir (Zovirax) (dose not specified) for one month (Briones et al. 2013)
- Trimethoprim-Sulfamethoxazole (Bactrim DS) (dose/frequency not specified) for six months (3 months in GELTAMO Z-BEAM LDCGB)
One course
Regimen variant #2
Study | Evidence |
---|---|
Fruchart et al. 2014 (ZBEAM2) | Phase 2 |
Targeted therapy
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days -21 & -14, given first on day -14
Radioconjugate therapy
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) by the following laboratory-based criteria:
- Platelet count 150 x 109/L or more: 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second
- Platelet count 100 up to 150 x 109/L: 0.3 mCi/kg (maximum dose of 32 mCi) IV once on day -14, given second
Chemotherapy
- Carmustine (BCNU) 300 mg/m2 IV once on day -7
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days -6 to -3
- Cytarabine (Ara-C) 200 mg/m2 IV every 12 hours on days -6 to -3
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
Supportive therapy
- Autologous stem cells re-infused on day 0
- "According to standard use"
One course
References
- Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. link to original article PubMed
- SHEBA-07-4466-AN-CTIL: Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00491491
- GELTAMO Z-BEAM LDCGB: Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed EudraCT 2007-003198-22
- ZBEAM2: Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00689169