Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{| class="wikitable" style="text-align:center; width:50%;"
 
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! colspan="2" align="center" style="color:white; font-size:125%; background-color:#4a1486" |'''Section editor'''
 
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| style="background-color:#F0F0F0" |[[File:Hilal.jpg|frameless|upright=0.3|center]]
 
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|<big>Talal Hilal, MD<br>University of Mississippi<br>Jackson, MS</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/THilalMD THilalMD]
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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<big>'''Note: most of these regimens include complex dose adjustments based on therapeutic troughs, concomitant medications, and other factors. Therefore, the focus on this page will be inclusion of drug names and references, but not necessarily drug dosages.'''</big>
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
−
==ASBMT==
 
−
*'''2012:''' Martin et al. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3404151/ First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation]
 
−
==EBMT/ELN==
 
−
*'''2013:''' Ruutu et al. [https://doi.org/10.1038/bmt.2013.107 Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice]
 
−
==ESBMT==
 
−
*'''2020:''' Penack et al. [https://doi.org/10.1016/s2352-3026(19)30256-x Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation]
 
−
=="How I Treat"==
 
−
*'''2020:''' Martin PJ. How I treat steroid-refractory acute graft-versus-host disease. Blood. 2020 May 7;135(19):1630-1638. [https://doi.org/10.1182/blood.2019000960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32202630 PubMed]
 
−
*'''2019:''' Sarantopoulos S, Cardones AR, Sullivan KM. How I treat refractory chronic graft-versus-host disease. Blood. 2019;133(11):1191-1200. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6418480/ link to PMC article]
 
−
*'''2014:''' Flowers ME, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015 Jan 22;125(4):606-15 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304105/ link to PMC article]
 
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=Prevention=
 
−
''This is very basic for now, to expand in the future. Information can also be found under individual regimens on the [[Allogeneic_HSCT|allogeneic HSCT]] page.''
 
−
==Cyclophosphamide, Mycophenolate mofetil, Tacrolimus==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8ajb82|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 50%" |Study
 
−
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633246/ Luznik et al. 2008]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[https://doi.org/10.1016/j.bbmt.2012.06.019 Solomon et al. 2012]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Mycophenolate mofetil (CellCept)]]
 
−
*[[Tacrolimus (Prograf)]]
 
−
</div></div>
 
−
===References===
 
−
#Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolaños-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. [https://doi.org/10.1016/j.bbmt.2008.03.005 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633246/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18489989 PubMed]
 
−
#Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012 Dec;18(12):1859-66. Epub 2012 Aug 1. [https://doi.org/10.1016/j.bbmt.2012.06.019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22863841 PubMed]
 
−
==Cyclophosphamide & Cyclosporine==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9134yg|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1182/bloodadvances.2021005847 Broers et al. 2022 (HOVON-96)]
 
−
|2013-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cyclosporine_.26_Mycophenolic_acid_88|CsA & MPA]]
 
−
| style="background-color:#1a9850" |Superior GRFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Cyclosporine]]
 
−
</div></div>
 
−
===References===
 
−
#'''HOVON-96:''' Broers AEC, de Jong CN, Bakunina K, Hazenberg MD, van Marwijk Kooy M, de Groot MR, van Gelder M, Kuball J, van der Holt B, Meijer E, Cornelissen JJ. Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial. Blood Adv. 2022 Jun 14;6(11):3378-3385. [https://doi.org/10.1182/bloodadvances.2021005847 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35143644/ PubMed] NL2128
 
−
==Cyclosporine & Methotrexate==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/92/7/2303.long Ratanatharathorn et al. 1998]
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Methotrexate_.26_Tacrolimus|Methotrexate & Tacrolimus]]
 
−
| style="background-color:#d73027" |Inferior aGVHD rate
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(09)70225-6 Finke et al. 2009 (AP-AS-21-DE)]
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclosporine.2C_Methotrexate.2C_ATG|Cyclosporine, MTX, ATG]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
| style="background-color:#eeee01" |Similar NRM
 
−
|-
 
−
|[https://doi.org/10.1182/blood.2020009050 Kennedy et al. 2021]
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclosporine.2C_MTX.2C_Tocilizumab_99|Cyclosporine, MTX, Tocilizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint
 
−
|style="background-color:#ffffbf" |Similar NRM
 
−
|-
 
−
|}
 
−
''Note: while AP-AS-21-DE did not meet its primary endpoint, there was a clear finding of superior control of cGVHD in the experimental arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine]]
 
−
*[[Methotrexate (MTX)]]
 
−
</div></div>
 
−
===References===
 
−
#Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998 Oct 1;92(7):2303-14. [http://www.bloodjournal.org/content/92/7/2303.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9746768 PubMed]
 
−
#'''AP-AS-21-DE:''' Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. Epub 2009 Aug 18. [https://doi.org/10.1016/S1470-2045(09)70225-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19695955 PubMed] NCT00655343
 
−
##'''Update:''' Socié G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Finke J; ATG-Fresenius Trial Group. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011 Jun 9;117(23):6375-82. Epub 2011 Apr 5. [http://www.bloodjournal.org/content/117/23/6375.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/21467544 PubMed]
 
−
##'''Update:''' Finke J, Schmoor C, Bethge WA, Ottinger H, Stelljes M, Volin L, Heim D, Bertz H, Grishina O, Socie G. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. Lancet Haematol. 2017 Jun;4(6):e293-e301. [https://doi.org/10.1016/s2352-3026(17)30081-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28583289/ PubMed]
 
−
# Kennedy GA, Tey SK, Buizen L, Varelias A, Gartlan KH, Curley C, Olver SD, Chang K, Butler JP, Misra A, Subramoniapillai E, Morton AJ, Durrant S, Henden AS, Moore J, Ritchie D, Gottlieb D, Cooney J, Paul SK, Hill GR. A phase 3 double-blind study of the addition of tocilizumab vs placebo to cyclosporin/methotrexate GVHD prophylaxis. Blood. 2021 Apr 8;137(14):1970-1979. [https://doi.org/10.1182/blood.2020009050 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33512442/ PubMed]
 
−
==Cyclosporine, Methotrexate, ATG==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(09)70225-6 Finke et al. 2009 (AP-AS-21-DE)]
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclosporine_.26_Methotrexate|Cyclosporine & MTX]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
| style="background-color:#eeee01" |Similar NRM
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(19)30220-0 Walker et al. 2020 (CBMTG 0801)]
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclosporine_.26_Methotrexate|Cyclosporine & MTX]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
| style="background-color:#ffffbf" |Similar NRM
 
−
|-
 
−
|}
 
−
''Note: while AP-AS-21-DE did not meet its primary endpoint, there was a clear finding of superior control of cGVHD in the experimental arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine|Cyclosporine]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Antithymocyte globulin, rabbit ATG (Grafalon)|Antithymocyte globulin, rabbit ATG (ATG-Fresenius)]]
 
−
</div></div>
 
−
===References===
 
−
#'''AP-AS-21-DE:''' Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009 Sep;10(9):855-64. Epub 2009 Aug 18. [https://doi.org/10.1016/S1470-2045(09)70225-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19695955 PubMed] NCT00655343
 
−
##'''Update:''' Socié G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Finke J; ATG-Fresenius Trial Group. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011 Jun 9;117(23):6375-82. Epub 2011 Apr 5. [http://www.bloodjournal.org/content/117/23/6375.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/21467544 PubMed]
 
−
##'''Update:''' Finke J, Schmoor C, Bethge WA, Ottinger H, Stelljes M, Volin L, Heim D, Bertz H, Grishina O, Socie G. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. Lancet Haematol. 2017 Jun;4(6):e293-e301. [https://doi.org/10.1016/s2352-3026(17)30081-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28583289/ PubMed]
 
−
#'''CBMTG 0801:''' Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Cell Therapy Transplant Canada. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020 Feb;7(2):e100-e111. Epub 2020 Jan 17. [https://doi.org/10.1016/S2352-3026(19)30220-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31958417 PubMed] NCT01217723
 
−
==Cyclosporine, Methotrexate, Methylprednisolone==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9126b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/96/7/2391.long Ruutu et al. 2000]
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclosporine_.26_Methotrexate|Cyclosporine & MTX]]
 
−
| style="background-color:#1a9850" |Lower rate of aGVHD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Methylprednisolone (Solumedrol)]]
 
−
</div></div>
 
−
===References===
 
−
#Ruutu T, Volin L, Parkkali T, Juvonen E, Elonen E. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. Blood. 2000 Oct 1;96(7):2391-8. [http://www.bloodjournal.org/content/96/7/2391.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11001889 PubMed]
 
−
##'''Update:''' Ruutu T, Nihtinen A, Niittyvuopio R, Juvonen E, Volin L. A randomized study of cyclosporine and methotrexate with or without methylprednisolone for the prevention of graft-versus-host disease: Improved long-term survival with triple prophylaxis. Cancer. 2018 Feb 15;124(4):727-733. Epub 2017 Nov 7. [https://doi.org/10.1002/cncr.31100 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29112242 PubMed]
 
−
==Cyclosporine, Methotrexate, Prednisone==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:81a6b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199310213291703 Chao et al. 1993]
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclosporine_.26_Prednisone_88|Cyclosporine & Prednisone]]
 
−
| style="background-color:#91cf60" |Seems to have lower rate of grade II to IV aGVHD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
#Chao NJ, Schmidt GM, Niland JC, Amylon MD, Dagis AC, Long GD, Nademanee AP, Negrin RS, O'Donnell MR, Parker PM, Smith EP, Snyder DS, Stein AS, Wong RM, Blume KG, Forman SJ. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med. 1993 Oct 21;329(17):1225-30. [https://doi.org/10.1056/NEJM199310213291703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8413388 PubMed]
 
−
==Cyclosporine & Mycophenolate mofetil==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:81a8h4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(19)30088-2 Sandmaier et al. 2019 (FH 2448.00)]
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclosporine.2C_Mycophenolate_mofetil.2C_Sirolimus|Cyclosporine, MMF, Sirolimus]]
 
−
| style="background-color:#d73027" |Higher rate of grade II to IV aGVHD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine]] 5 mg/kg PO twice per day from day -3 to day +96, then tapered off by day +150 in the absence of GVHD
 
−
*[[Mycophenolate mofetil (CellCept)]] 15 mg/kg PO three times per day from day 0 to day +30, then 15 mg/kg PO twice per day from day +31 to day +150, then tapered off by day +180 in the absence of GVHD
 
−
</div></div>
 
−
===References===
 
−
#'''FH 2448.00:''' Sandmaier BM, Kornblit B, Storer BE, Olesen G, Maris MB, Langston AA, Gutman JA, Petersen SL, Chauncey TR, Bethge WA, Pulsipher MA, Woolfrey AE, Mielcarek M, Martin PJ, Appelbaum FR, Flowers MED, Maloney DG, Storb R. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial. Lancet Haematol. 2019 Aug;6(8):e409-e418. Epub 2019 Jun 24. [https://doi.org/10.1016/S2352-3026(19)30088-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31248843 PubMed] NCT01231412
 
−
==Cyclosporine, Mycophenolate mofetil, Sirolimus==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8ajb82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(19)30088-2 Sandmaier et al. 2019 (FH 2448.00)]
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cyclosporine_.26_Mycophenolate_mofetil|Cyclosporine & MMF]]
 
−
| style="background-color:#1a9850" |Lower rate of grade II to IV aGVHD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine]] 5 mg/kg PO twice per day from day -3 to day +96, then tapered off by day +150 in the absence of GVHD
 
−
*[[Mycophenolate mofetil (CellCept)]] 15 mg/kg PO three times per day from day 0 to day +30, then 15 mg/kg PO twice per day from day +31 to day +150, then tapered off by day +180 in the absence of GVHD
 
−
*[[Sirolimus (Rapamune)]] 2 mg PO once per day from day -3 to day +150 (adjusted to maintain trough level of 3 to 12 ng/mL), then tapered off by day +180 in the absence of GVHD
 
−
</div></div>
 
−
===References===
 
−
#'''FH 2448.00:''' Sandmaier BM, Kornblit B, Storer BE, Olesen G, Maris MB, Langston AA, Gutman JA, Petersen SL, Chauncey TR, Bethge WA, Pulsipher MA, Woolfrey AE, Mielcarek M, Martin PJ, Appelbaum FR, Flowers MED, Maloney DG, Storb R. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial. Lancet Haematol. 2019 Aug;6(8):e409-e418. Epub 2019 Jun 24. [https://doi.org/10.1016/S2352-3026(19)30088-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31248843 PubMed] NCT01231412
 
−
==Methotrexate & Tacrolimus==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/92/7/2303.long Ratanatharathorn et al. 1998]
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclosporine_.26_Methotrexate|Cyclosporine & Methotrexate]]
 
−
| style="background-color:#1a9850" |Superior aGVHD rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Tacrolimus (Prograf)]]
 
−
</div></div>
 
−
===References===
 
−
#Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998 Oct 1;92(7):2303-14. [http://www.bloodjournal.org/content/92/7/2303.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9746768 PubMed]
 
−
==Methotrexate, Tacrolimus, Tocilizumab {{#subobject:fe1c2e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2d492b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865423/ Drobyski et al. 2018]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Tacrolimus (Prograf)]]
 
−
*[[Tocilizumab (Actemra)]]
 
−
</div></div>
 
−
===References===
 
−
#Drobyski WR, Szabo A, Zhu F, Keever-Taylor C, Hebert KM, Dunn R, Yim S, Johnson B, D'Souza A, Eapen M, Fenske TS, Hari P, Hamadani M, Horowitz MM, Rizzo JD, Saber W, Shah N, Shaw B, Pasquini M. Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft-versus-host disease: low incidence of lower gastrointestinal tract disease. Haematologica. 2018 Apr;103(4):717-727. Epub 2018 Jan 19. [http://www.haematologica.org/content/103/4/717 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865423/ linkt o PMC article] [https://pubmed.ncbi.nlm.nih.gov/29351985 PubMed]
 
−
==Methotrexate, Tacrolimus, Vorinostat {{#subobject:ca16a7|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:191ac5|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/15/1760.long Choi et al. 2017]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Methotrexate (MTX)]] 5 mg/m<sup>2</sup> IV once per day on days +1, +3, +6, +11
 
−
*[[Tacrolimus (Prograf)]] by one of the following routes, starting on day -3:
 
−
**IV: 0.03 mg/kg/day
 
−
**PO: 0.045 mg/kg/day
 
−
**Goal trough level of 8 to 12 ng/mL
 
−
**In absence of GVHD, tapering begins on day +100 and completes on day +180
 
−
*[[Vorinostat (Zolinza)]] 100 mg PO twice per day on days -10 to +100
 
−
</div></div>
 
−
===References===
 
−
#Choi SW, Braun T, Henig I, Gatza E, Magenau J, Parkin B, Pawarode A, Riwes M, Yanik G, Dinarello CA, Reddy P. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. Blood. 2017 Oct 12;130(15):1760-1767. Epub 2017 Aug 7. [http://www.bloodjournal.org/content/130/15/1760.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28784598 PubMed]
 
−
==Rabbit ATG==
 
−
====Immunosuppressive therapy====
 
−
*[[Antithymocyte globulin, rabbit ATG (Thymoglobulin)]]
 
−
</div></div>
 
−
===References===
 
−
#Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, Foley R; Canadian Blood and Marrow Transplant Group. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016 Feb;17(2):164-173. Epub 2015 Dec 24. [https://doi.org/10.1016/s1470-2045(15)00462-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26723083 PubMed] ISRCTN29899028
 
−
#'''ATGFamilyStudy:''' Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, Nagler A, Selleri C, Risitano A, Messina G, Bethge W, Pérez de Oteiza J, Duarte R, Carella AM, Cimminiello M, Guidi S, Finke J, Mordini N, Ferra C, Sierra J, Russo D, Petrini M, Milone G, Benedetti F, Heinzelmann M, Pastore D, Jurado M, Terruzzi E, Narni F, Völp A, Ayuk F, Ruutu T, Bonifazi F. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016 Jan 7;374(1):43-53. [https://doi.org/10.1056/NEJMoa1506002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26735993 PubMed] NCT00678275
 
−
#'''ProfGVHD1:''' Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, Pession A, Fagioli F, Favre C, Lanino E, Giorgiani G, Merli P, Pagliara D, Prete A, Zecca M. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1126-1136. Epub 2017 Jul 10. [https://doi.org/10.1016/s1470-2045(17)30417-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28705454 PubMed] NCT00934557
 
−
==Sitagliptin, Sirolimus, Tacrolimus==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9134b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7845486/ Farag et al. 2021 (IUSCC-0522)]
 
−
|2016-2018
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Sitagliptin (Januvia)]]
 
−
*[[Sirolimus (Rapamune)]]
 
−
*[[Tacrolimus (Prograf)]]
 
−
</div></div>
 
−
===References===
 
−
#'''IUSCC-0522:''' Farag SS, Abu Zaid M, Schwartz JE, Thakrar TC, Blakley AJ, Abonour R, Robertson MJ, Broxmeyer HE, Zhang S. Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. N Engl J Med. 2021 Jan 7;384(1):11-19. [https://doi.org/10.1056/nejmoa2027372 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7845486/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33406328 PubMed] NCT02683525
 
−
=Treatment, aGVHD, all lines of therapy=
 
−
==Ruxolitinib monotherapy {{#subobject:05e2b6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bhy62c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc7229262/ Jagasia et al. 2020 (REACH1)]
 
−
|2016-2018
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1917635 Zeiser et al. 2020 (REACH2)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Investigator's choice
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
 
−
'''Continued for at least 56 days, tapered thereafter'''
 
−
</div></div>
 
−
===References===
 
−
#'''REACH2:''' Zeiser R, von Bubnoff N, Butler J, Mohty M, Niederwieser D, Or R, Szer J, Wagner EM, Zuckerman T, Mahuzier B, Xu J, Wilke C, Gandhi KK, Socié G; REACH2 Trial Group. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N Engl J Med. 2020 May 7;382(19):1800-1810. Epub 2020 Apr 22. [https://doi.org/10.1056/nejmoa1917635 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32320566 PubMed] NCT02913261
 
−
#'''REACH1:''' Jagasia M, Perales MA, Schroeder MA, Ali H, Shah NN, Chen YB, Fazal S, Dawkins FW, Arbushites MC, Tian C, Connelly-Smith L, Howell MD, Khoury HJ. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14;135(20):1739-1749. [https://doi.org/10.1182/blood.2020004823 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7229262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32160294/ PubMed] NCT02953678
 
−
=Treatment, cGVHD, all lines of therapy=
 
−
==Cyclosporine & Prednisone {{#subobject:7a7c79|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c940ce|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bbmt.org/article/S1083-8791(01)50043-9 Arora et al. 2001]
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Cyclosporine.2C_Prednisone.2C_Thalidomide_99|Cyclosporine, Prednisone, Thalidomide]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine|Cyclosporine]]
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
#Arora M, Wagner JE, Davies SM, Blazar BR, Defor T, Enright H, Miller WJ, Weisdorf DF. Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2001;7(5):265-73. [http://www.bbmt.org/article/S1083-8791(01)50043-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11400948 PubMed]
 
−
==Cyclosporine, Corticosteroids, Rituximab {{#subobject:9fffb0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0de254|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/20/2186.long Malard et al. 2017]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d4d4d4" |ORR at 12 mo: 83%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine|Cyclosporine]] 6 mg/kg PO twice per day
 
−
**Or, continued at the dose at time of study entry
 
−
**Goal level 200 to 400 ng/mL
 
−
*[[:Category:Steroids|Corticosteroids]] equivalent to 1 mg/kg/day of [[Prednisone (Sterapred)]]
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
''Rituximab given as a 4-week course, repeated one month later if PR or better. Corticosteroids and CsA tapered per standard of care.''
 
−
</div></div>
 
−
===References===
 
−
#Malard F, Labopin M, Yakoub-Agha I, Chantepie S, Guillaume T, Blaise D, Tabrizi R, Magro L, Vanhove B, Blancho G, Moreau P, Gaugler B, Chevallier P, Mohty M. Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study. Blood. 2017 Nov 16;130(20):2186-2195. Epub 2017 Sep 1. [http://www.bloodjournal.org/content/130/20/2186.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28864814 PubMed]
 
−
==Cyclosporine, Sirolimus, Prednisone {{#subobject:1ffc79|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cc1bce|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.haematologica.org/content/103/11/1915 Carpenter et al. 2018 (BMT CTN 0801)]
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Sirolimus_.26_Prednisone_99|Sirolimus & Prednisone]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Cyclosporine|Cyclosporine]]
 
−
*[[Sirolimus (Rapamune)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
#'''BMT CTN 0801:''' Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolaños-Meade J, Sarantopoulos S, Alousi AM, Abhyankar S, Waller EK, Mendizabal A, Zhu J, O'Brien KA, Lazaryan A, Wu J, Nemecek ER, Pavletic SZ, Cutler CS, Horowitz MM, Arora M; BMT CTN. A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801. Haematologica. 2018 Nov;103(11):1915-1924. Epub 2018 Jun 28. [http://www.haematologica.org/content/103/11/1915 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29954931 PubMed]
 
−
==Ibrutinib monotherapy {{#subobject:5d9394|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7f34b4|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/130/21/2243.long Miklos et al. 2017 (PCYC-1129-CA)]
 
−
| style="background-color:#91cf61" |Phase 1b/2 (RT)
 
−
| style="background-color:#bfd3e6" |Best ORR: 67%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Ibrutinib (Imbruvica)]] 420 mg PO once per day
 
−
</div></div>
 
−
===References===
 
−
#'''PCYC-1129-CA:''' Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, Flowers ME, Logan AC, Nakamura R, Blazar BR, Li Y, Chang S, Lal I, Dubovsky J, James DF, Styles L, Jaglowski S. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 Nov 23;130(21):2243-2250. Epub 2017 Sep 18. [http://www.bloodjournal.org/content/130/21/2243.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28924018 PubMed] NCT02195869
 
−
==Ruxolitinib monotherapy {{#subobject:05e2b6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bhy62c|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years 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/10.1056/nejmoa2033122 Zeiser et al. 2021 (REACH3)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 
−
|Best available therapy
 
−
| style="background-color:#1a9850" |Superior ORR at week 24
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
 
−
'''28-day cycle for at least 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REACH3:''' Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. [https://doi.org/10.1056/nejmoa2033122 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34260836/ PubMed] NCT03112603
 
−
==Sirolimus, Tacrolimus, Prednisone {{#subobject:05e07b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bc128c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |Comparator
 
−
! style="width: 25%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.haematologica.org/content/103/11/1915 Carpenter et al. 2018 (BMT CTN 0801)]
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Sirolimus_.26_Prednisone_99|Sirolimus & Prednisone]]
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunosuppressive therapy====
 
−
*[[Sirolimus (Rapamune)]]
 
−
*[[Tacrolimus (Prograf)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
#'''BMT CTN 0801:''' Carpenter PA, Logan BR, Lee SJ, Weisdorf DJ, Johnston L, Costa LJ, Kitko CL, Bolaños-Meade J, Sarantopoulos S, Alousi AM, Abhyankar S, Waller EK, Mendizabal A, Zhu J, O'Brien KA, Lazaryan A, Wu J, Nemecek ER, Pavletic SZ, Cutler CS, Horowitz MM, Arora M; BMT CTN. A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801. Haematologica. 2018 Nov;103(11):1915-1924. Epub 2018 Jun 28. [http://www.haematologica.org/content/103/11/1915 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29954931 PubMed]
 
−
=Response criteria=
 
−
==2005 NIH cGVHD Consensus Panel==
 
−
</div></div>
 
−
===References===
 
−
#Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G, Schubert M, Berger A, Bross P, Chien JW, Couriel D, Dunn JP, Fall-Dickson J, Farrell A, Flowers ME, Greinix H, Hirschfeld S, Gerber L, Kim S, Knobler R, Lachenbruch PA, Miller FW, Mittleman B, Papadopoulos E, Parsons SK, Przepiorka D, Robinson M, Ward M, Reeve B, Rider LG, Shulman H, Schultz KR, Weisdorf D, Vogelsang GB; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006 Mar;12(3):252-66. [http://www.bbmt.org/article/S1083-8791(06)00070-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/16503494 PubMed]
 
−
==2014 NIH Response Criteria==
 
−
</div></div>
 
−
===References===
 
−
#Lee SJ, Wolff D, Kitko C, Koreth J, Inamoto Y, Jagasia M, Pidala J, Olivieri A, Martin PJ, Przepiorka D, Pusic I, Dignan F, Mitchell SA, Lawitschka A, Jacobsohn D, Hall AM, Flowers ME, Schultz KR, Vogelsang G, Pavletic S. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol Blood Marrow Transplant. 2015 Jun;21(6):984-99. Epub 2015 Mar 19. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744804/ link to PMC article]
 
−
=Scoring=
 
−
==Glucksberg acute graft versus host (GVHD) scores==
 
−
===Skin===
 
−
*Stage 0: No rash
 
−
*Stage 1: Maculopapular rash <25% of body surface area
 
−
*Stage 2: Maculopapular rash on 25-50% of body surface area
 
−
*Stage 3: Generalized erythroderma
 
−
*Stage 4: Generalized erythroderma with bullous formation and desquamation
 
−
===Liver===
 
−
*Stage 0: Bilirubin <2 mg/dL
 
−
*Stage 1: Bilirubin 2-3 mg/dL
 
−
*Stage 2: Bilirubin 3.01-6 mg/dL
 
−
*Stage 3: Bilirubin 6.01-15 mg/dL
 
−
*Stage 4: Bilirubin >15 mg/dL
 
−
===GI===
 
−
*Stage 0: No diarrhea, or diarrhea less than 500 mL/day
 
−
*Stage 1: Diarrhea 500-999 mL/day
 
−
*Stage 2: Diarrhea 1000-1499 mL/day
 
−
*Stage 3: Diarrhea >1500 mL/day
 
−
*Stage 4: Severe abdominal pain, with or without ileus
 
−
===Glucksberg grade===
 
−
{| class="wikitable" style="text-align:center;"
 
−
! align="left" |Overall grade
 
−
!I
 
−
!II
 
−
!III
 
−
!IV
 
−
|-
 
−
| align="left" |Skin
 
−
|1-2
 
−
|1-3
 
−
|2-3
 
−
|2-4
 
−
|-
 
−
| align="left" |GI
 
−
|0
 
−
|1
 
−
|2-3
 
−
|2-4
 
−
|-
 
−
| align="left" |Liver
 
−
|0
 
−
|1
 
−
|2-4
 
−
|2-4
 
−
|-
 
−
|Karnofsky performance scale
 
−
|90-100%
 
−
|70-80%
 
−
|50-60%
 
−
|30-40%
 
−
|-
 
−
|}
 
−
===IBMTR severity index===
 
−
The severity is the highest level which the patient reaches based on separate skin, liver, and GI staging.
 
−
{| class="wikitable" style="text-align:center;"
 
−
! align="left" |Overall grade
 
−
!A
 
−
!B
 
−
!C
 
−
!D
 
−
|-
 
−
| align="left" |Skin
 
−
|1
 
−
|2
 
−
|3
 
−
|4
 
−
|-
 
−
| align="left" |GI
 
−
|0
 
−
|1-2
 
−
|3
 
−
|4
 
−
|-
 
−
| align="left" |Liver
 
−
|0
 
−
|1-2
 
−
|3
 
−
|4
 
−
|-
 
−
|}
 
−
==Chronic GVHD==
 
−
===Localized===
 
−
*Localized skin and/or liver dysfunction due to chronic GVHD
 
−
===Extensive===
 
−
*Generalized skin involvement or localized skin and/or liver dysfunction due to chronic GVHD '''plus at least one of the following''':
 
−
**Liver biopsy showing cirrhosis, chronic aggressive hepatitis, bridging necrosis
 
−
**Eye involvement, defined as [http://en.wikipedia.org/wiki/Schirmer's_test Schirmer's test] with less than 5 mm wetting
 
−
**Involvement of oral mucosa on lip biopsy or minor salivary glands
 
−
**Other organ involvement
 
−
*Overall severity categories: mild/moderate/severe
 
−
==References==
 
−
#Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975 Apr 17;292(16):832-43 [https://doi.org/10.1056/NEJM197504172921605 link to original article] [https://pubmed.ncbi.nlm.nih.gov/234595 PubMed]
 
−
#Thomas ED, Storb R, Clift RA, Fefer A, Johnson L, Neiman PE, Lerner KG, Glucksberg H, Buckner CD. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975 Apr 24;292(17):895-902 [https://doi.org/10.1056/NEJM197504242921706 link to original article] '''(contains staging scale)''' [https://pubmed.ncbi.nlm.nih.gov/235092 PubMed]
 
−
#Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, Cahn JY, Calderwood S, Gratwohl A, Socié G, Abecasis MM, Sobocinski KA, Zhang MJ, Horowitz MM. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997 Jun;97(4):855-64. [https://doi.org/10.1046/j.1365-2141.1997.1112925.x/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/9217189 PubMed]
 
−
[[Category:Graft versus host disease regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Alloimmune hematologic conditions]]
 

Latest revision as of 00:13, 18 June 2023

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