Difference between revisions of "Graft versus host disease"
Jump to navigation
Jump to search
Warner-admin (talk | contribs) m (Text replacement - "Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site." to "<!-- Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site. -->") |
Warner-admin (talk | contribs) m (Text replacement - "'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.'''" to "<!--'''Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer. If this is your first time visiting, we suggest you read the tutorial.'''-->") |
||
Line 1: | Line 1: | ||
− | '''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].''' | + | <!--'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].'''--> |
<!-- | <!-- |
Revision as of 18:44, 15 March 2018
Section editor | |
---|---|
Aric C. Hall, MD Madison, WI Twitter: AricHall1 |
9 regimens on this page
16 variants on this page
|
Guidelines
"How we treat"
Prevention
This is very basic for now, to expand in the future. Information can also be found under individual regimens on the allogeneic HSCT page.
Cyclosporine, Methotrexate, ATG
References
- 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. PubMed
Cyclosporine, Methotrexate, MP
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. link to original article 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. link to original article PubMed
Methotrexate, Tacrolimus, Vorinostat
back to top |
Regimen
Study | Evidence |
---|---|
Choi et al. 2017 | Phase II |
Immunosuppressive therapy
- Methotrexate (MTX) 5 mg/m2 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 BID on days -10 to +100
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. link to original article contains verified protocol PubMed
Rabbit ATG
Immunosuppressive therapy
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. PubMed
- 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. link to original article PubMed
- 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. PubMed
Treatment, aGVHD
Treatment, cGVHD
Cyclosporine & Prednisone
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Arora et al. 2001 | RCT | Cyclosporine, Prednisone, Thalidomide | Seems not superior |
To be completed
Immunosuppressive therapy
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. link to original article PubMed
Cyclosporine, Corticosteroids, Rituximab
back to top |
Regimen
Study | Evidence | Efficacy |
---|---|---|
Malard et al. 2017 | Phase II | ORR at 12 mo: 83% |
Immunosuppressive therapy
- Cyclosporine 6 mg/kg PO BID
- Or, continued at the dose at time of study entry
- Goal level 200 to 400 ng/mL
- Corticosteroids equivalent to 1 mg/kg/day of Prednisone (Sterapred)
- Rituximab (Rituxan) 375 mg/m2 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.
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. link to original article contains verified protocol PubMed
Ibrutinib monotherapy
back to top |
Regimen
Study | Evidence | Efficacy |
---|---|---|
Miklos et al. 2017 | Phase 1b/2 | Best ORR: 67% |
Immunosuppressive therapy
- Ibrutinib (Imbruvica) 420 mg PO once per day
References
- 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. link to original article contains verified protocol PubMed
Response criteria
2005 NIH cGVHD Consensus Panel
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. link to original article PubMed
2014 NIH Response Criteria
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. 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 6.01-15.0 mg/dL
- Stage 4: Bilirubin >15 mg/dL
GI
- Stage 0: No diarrhea, or diarrhea <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
Overall grade | I | II | III | IV |
---|---|---|---|---|
Skin | 1-2 | 1-3 | 2-3 | 2-4 |
GI | 0 | 1 | 2-3 | 2-4 |
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.
Overall grade | A | B | C | D |
---|---|---|---|---|
Skin | 1 | 2 | 3 | 4 |
GI | 0 | 1-2 | 3 | 4 |
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 Schirmer's test with <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 link to original article 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 link to original article (contains staging scale) 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. link to original article PubMed