Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
International Journal of Hematology
Published in: International Journal of Hematology 5/2015

01-05-2015 | Progress in Hematology

State-of-the-art acute and chronic GVHD treatment

Authors: Muhammad Omer Jamil, Shin Mineishi

Published in: International Journal of Hematology | Issue 5/2015

Login to get access

Abstract

Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.
Literature
1.
Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957;257(11):491–6.PubMed
2.
Pasquini MC WZ. Current use and outcome of hematopoietic stem cell transplantation. CIBMTR Summary Slides. 2013.
3.
Appelbaum FR. Haematopoietic cell transplantation as immunotherapy. Nature. 2001;411(6835):385–9.PubMed
4.
Russell NH, Kjeldsen L, Craddock C, et al. A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia. Leukemia. 2014.
5.
Kekre N, Antin JH. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood. 2014;124(3):334–43.PubMed
6.
Solh M. Haploidentical vs cord blood transplantation for adults with acute myelogenous leukemia. World J Stem Cells. 2014;6(4):371–9.PubMedCentralPubMed
7.
Billingham RE. The biology of graft-versus-host reactions. Harvey Lect. 1966;62:21–78.PubMed
8.
Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76(8):1464–72.PubMed
9.
Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28(3):250–9.PubMed
10.
Filipovich AH, Weisdorf D, Pavletic S, National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease, et al. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56.PubMed
11.
Griffith LM, Pavletic SZ, Lee SJ, Martin PJ, Schultz KR, Vogelsang GB. Chronic graft-versus-host disease–implementation of the national institutes of health consensus criteria for clinical trials. Biol Blood Marrow Transplant. 2008;14:379–84.PubMedCentralPubMed
12.
Jagasia MH, Greinix HT, Arora M, National Institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2014;21:389–401.PubMed
13.
Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100(2):406–14.PubMed
14.
Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to national institutes of health consensus criteria. Blood. 2011;117(11):3214–9.PubMedCentralPubMed
15.
MacMillan ML, Weisdorf DJ, Wagner JE, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant. 2002;8(7):387–94.PubMed
16.
Koc S, Leisenring W, Flowers ME, et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood. 2002;100(1):48–51.PubMed
17.
Shlomchik WD. Graft-versus-host disease. Nat Rev Immunol. 2007;7(5):340–52.PubMed
18.
19.
Xun CQ, Thompson JS, Jennings CD, Brown SA, Widmer MB. Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice. Blood. 1994;83(8):2360–7.PubMed
20.
Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90(8):3204–13.PubMed
21.
Hill GR, Ferrara JL. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood. 2000;95(9):2754–9.PubMed
22.
Choi SW, Kitko CL, Braun T, et al. Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival. Blood. 2008;112(4):1539–42.PubMedCentralPubMed
23.
Murai M, Yoneyama H, Ezaki T, et al. Peyer’s patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat Immunol. 2003;4(2):154–60.PubMed
24.
Couriel DR, Saliba RM, Giralt S, et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2004;10(3):178–85.PubMed
25.
Sorror ML, Maris MB, Storer B, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104(4):961–8.PubMed
26.
Duffner UA, Maeda Y, Cooke KR, et al. Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease. J Immunol. 2004;172(12):7393–8.PubMed
27.
Sato K, Yamashita N, Baba M, Matsuyama T. Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity. 2003;18(3):367–79.PubMed
28.
Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371(9624):1579–86.PubMed
29.
Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363(9419):1439–41.PubMed
30.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124(4):783–801.PubMed
31.
Dustin ML. Role of adhesion molecules in activation signaling in T lymphocytes. J Clin Immunol. 2001;21(4):258–63.PubMed
32.
Korngold R, Sprent J. Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers. J Exp Med. 1982;155(3):872–83.PubMed
33.
Korngold R, Sprent J. Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J Immunol. 1985;135(5):3004–10.PubMed
34.
Cohen JL, Boyer O. The role of CD4+ CD25 hi regulatory T cells in the physiopathogeny of graft-versus-host disease. Curr Opin Immunol. 2006;18(5):580–5.PubMed
35.
Zeng D, Lewis D, Dejbakhsh-Jones S, et al. Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J Exp Med. 1999;189(7):1073–81.PubMedCentralPubMed
36.
Lowsky R, Takahashi T, Liu YP, et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005;353(13):1321–31.PubMed
37.
Ratanatharathorn V, Nash RA, Przepiorka D, et al. 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;92(7):2303–14.PubMed
38.
Zeiser R, Nguyen VH, Beilhack A, et al. Inhibition of CD4+ CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108(1):390–9.PubMedCentralPubMed
39.
Fowler DH, Kurasawa K, Smith R, Eckhaus MA, Gress RE. Donor CD4-enriched cells of Th2 cytokine phenotype regulate graft-versus-host disease without impairing allogeneic engraftment in sublethally irradiated mice. Blood. 1994;84(10):3540–9.PubMed
40.
Yang YG, Dey BR, Sergio JJ, Pearson DA, Sykes M. Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12. J Clin Invest. 1998;102(12):2126–35.PubMedCentralPubMed
41.
Reddy P, Ferrara JL. Graft-Versus-Host Disease and Graft-Versus-Leukemia Responses. In: Hoffman RB, Edward J, Edward Silberstein J, Leslie Heslop E, Helen E, Jeffrey I, Anastasi I, John, editors. Basic principles and practice. USA: Hematology; 2013. p. 1592–611.
42.
Ferrara JL, Reddy P. Pathophysiology of graft-versus-host disease. Semin Hematol. 2006;43(1):3–10.PubMed
43.
Krenger W, Falzarano G, Delmonte J Jr, Snyder KM, Byon JC, Ferrara JL. Interferon-gamma suppresses T-cell proliferation to mitogen via the nitric oxide pathway during experimental acute graft-versus-host disease. Blood. 1996;88(3):1113–21.PubMed
44.
Reddy P, Teshima T, Kukuruga M, et al. Interleukin-18 regulates acute graft-versus-host disease by enhancing fas-mediated donor T cell apoptosis. J Exp Med. 2001;194(10):1433–40.PubMedCentralPubMed
45.
Banovic T, MacDonald KP, Morris ES, et al. TGF-beta in allogeneic stem cell transplantation: friend or foe? Blood. 2005;106(6):2206–14.PubMed
46.
Lin MT, Storer B, Martin PJ, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med. 2003;349(23):2201–10.PubMed
47.
Ferrara JL, Deeg HJ. Graft-versus-host disease. N Engl J Med. 1991;324(10):667–74.PubMed
48.
Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol. 2007;25:139–70.PubMed
49.
van den Brink MR, Burakoff SJ. Cytolytic pathways in haematopoietic stem-cell transplantation. Nat Rev Immunol. 2002;2(4):273–81.PubMed
50.
Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS. Leukocyte migration and graft-versus-host disease. Blood. 2005;105(11):4191–9.PubMedCentralPubMed
51.
Waldman E, Lu SX, Hubbard VM, et al. Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood. 2006;107(4):1703–11.PubMedCentralPubMed
52.
Welniak LA, Kuprash DV, Tumanov AV, et al. Peyer patches are not required for acute graft-versus-host disease after myeloablative conditioning and murine allogeneic bone marrow transplantation. Blood. 2006;107(1):410–2.PubMedCentralPubMed
53.
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5(10):987–95.PubMed
54.
Hill GR, Teshima T, Rebel VI, et al. The p55 TNF-alpha receptor plays a critical role in T cell alloreactivity. J Immunol. 2000;164(2):656–63.PubMed
55.
Piguet PF, Grau GE, Allet B, Vassalli P. Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs -host disease. J Exp Med. 1987;166(5):1280–9.PubMed
56.
Brown GR, Lee E, Thiele DL. TNF-TNFR2 interactions are critical for the development of intestinal graft-versus-host disease in MHC class II-disparate (C57BL/6 J–> C57BL/6 J × bm12)F1 mice. J Immunol. 2002;168(6):3065–71.PubMed
57.
Krenger W, Hollander GA. The thymus in GVHD pathophysiology. Best Pract Res Clin Haematol. 2008;21(2):119–28.PubMed
58.
Martin PJ. Biology of chronic graft-versus-host disease: implications for a future therapeutic approach. Keio J Med. 2008;57(4):177–83.PubMedCentralPubMed
59.
Shimabukuro-Vornhagen A, Hallek MJ, Storb RF, von Bergwelt-Baildon MS. The role of B cells in the pathogenesis of graft-versus-host disease. Blood. 2009;114(24):4919–27.PubMed
60.
Kapur R, Ebeling S, Hagenbeek A. B-cell involvement in chronic graft-versus-host disease. Haematologica. 2008;93(11):1702–11.PubMed
61.
Chan I, Oyama N, Neill SM, Wojnarowska F, Black MM, McGrath JA. Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Clin Exp Dermatol. 2004;29(5):499–504.PubMed
62.
Bates JS, Engemann AM, Hammond JM. Clinical utility of rituximab in chronic graft-versus-host disease. Ann Pharmacother. 2009;43(2):316–21.PubMed
63.
Cosmi L, Liotta F, Angeli R, et al. Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines. Blood. 2004;103(8):3117–21.PubMed
64.
Anderson BE, McNiff JM, Matte C, Athanasiadis I, Shlomchik WD, Shlomchik MJ. Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease. Blood. 2004;104(5):1565–73.PubMed
65.
Miura Y, Thoburn CJ, Bright EC, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood. 2004;104(7):2187–93.PubMed
66.
Zhang C, Todorov I, Zhang Z, et al. Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestations. Blood. 2006;107(7):2993–3001.PubMed
67.
Auffermann-Gretzinger S, Lossos IS, Vayntrub TA, et al. Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients. Blood. 2002;99(4):1442–8.PubMed
68.
Klangsinsirikul P, Carter GI, Byrne JL, Hale G, Russell NH. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood. 2002;99(7):2586–91.PubMed
69.
Chan GW, Gorgun G, Miller KB, Foss FM. Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9(3):170–6.PubMed
70.
Teshima T, Ordemann R, Reddy P, et al. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat Med. 2002;8:575–81.PubMed
71.
Fujita S, Sato Y, Sato K, et al. Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+ CD25 + Foxp3+ regulatory T cells. Blood. 2007;110(10):3793–803.PubMed
72.
Marcondes AM, Karoopongse E, Lesnikova M, et al. Alpha-1-antitrypsin (AAT)-modified donor cells suppress GVHD but enhance the GVL effect: a role for mitochondrial bioenergetics. Blood. 2014;124(18):2881–91.PubMed
73.
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295–304.PubMed
74.
Gratwohl A, Hermans J, Apperley J, et al. Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. working party chronic leukemia of the European Group for Blood and Marrow Transplantation. Blood. 1995;86(2):813–8.PubMed
75.
MacMillan ML, Weisdorf DJ, Davies SM, et al. Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(1):40–6.PubMed
76.
Weisdorf D, Haake R, Blazar B, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75(4):1024–30.PubMed
77.
Saliba RM, Couriel DR, Giralt S, et al. Prognostic value of response after upfront therapy for acute GVHD. Bone Marrow Transplant. 2012;47(1):125–31.PubMedCentralPubMed
78.
Van Lint MT, Uderzo C, Locasciulli A, et al. Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood. 1998;92(7):2288–93.PubMed
79.
Mielcarek M, Storer BE, Boeckh M, et al. Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Blood. 2009;113(13):2888–94.PubMedCentralPubMed
80.
Hings IM, Filipovich AH, Miller WJ, et al. Prednisone therapy for acute graft-versus-host disease: short- versus long-term treatment. A prospective randomized trial. Transplantation. 1993;56(3):577–80.PubMed
81.
Alousi AM, Weisdorf DJ, Logan BR, et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the blood and marrow transplant clinical trials network. Blood. 2009;114(3):511–7.PubMedCentralPubMed
82.
Bolaños-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, Carter SL, Goldstein SC, Hexner EO, Horowitz MM, Lee SJ, Levine JE, MacMillan ML, Martin PJ, Mendizabal AM, Nakamura R, Pasquini MC, Weisdorf DJ, Westervelt P, Ho VT. Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014;124(22):3221–7.PubMed
83.
Cahn JY, Bordigoni P, Tiberghien P, et al. Treatment of acute graft-versus-host disease with methylprednisolone and cyclosporine with or without an anti-interleukin-2 receptor monoclonal antibody. A multicenter phase III study. Transplantation. 1995;60(9):939–42.PubMed
84.
Lee SJ, Zahrieh D, Agura E, et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood. 2004;104(5):1559–64.PubMed
85.
Cragg L, Blazar BR, Defor T, et al. A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6(4a):441–7.PubMed
86.
Levine JE, Paczesny S, Mineishi S, et al. Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease. Blood. 2008;111(4):2470–5.PubMedCentralPubMed
87.
Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15(12):1555–62.PubMedCentralPubMed
88.
Dignan FL, Amrolia P, Clark A, et al. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158(1):46–61.PubMed
89.
Van Lint MT, Milone G, Leotta S, et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood. 2006;107(10):4177–81.PubMed
90.
Gomez-Almaguer D, Ruiz-Arguelles GJ, del Carmen Tarin-Arzaga L, et al. Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2008;14(1):10–5.PubMed
91.
Martinez C, Solano C, Ferra C, Sampol A, Valcarcel D, Perez-Simon JA. Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study. Biol Blood Marrow Transplant. 2009;15(5):639–42.PubMed
92.
Bordigoni P, Dimicoli S, Clement L, et al. Daclizumab, an efficient treatment for steroid-refractory acute graft-versus-host disease. Br J Haematol. 2006;135(3):382–5.PubMed
93.
Srinivasan R, Chakrabarti S, Walsh T, et al. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol. 2004;124(6):777–86.PubMed
94.
Bay JO, Dhedin N, Goerner M, et al. Inolimomab in steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: retrospective analysis and comparison with other interleukin-2 receptor antibodies. Transplantation. 2005;80(6):782–8.PubMed
95.
Schmidt-Hieber M, Fietz T, Knauf W, et al. Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease. Br J Haematol. 2005;130(4):568–74.PubMed
96.
Ehlers S. Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis. 2005;41(Suppl 3):S199–203.PubMed
97.
Couriel D, Saliba R, Hicks K, et al. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood. 2004;104(3):649–54.PubMed
98.
Marty FM, Lee SJ, Fahey MM, et al. Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood. 2003;102(8):2768–76.PubMed
99.
Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45–52.PubMed
100.
Sleight BS, Chan KW, Braun TM, Serrano A, Gilman AL. Infliximab for GVHD therapy in children. Bone Marrow Transplant. 2007;40(5):473–80.PubMed
101.
Patriarca F, Sperotto A, Damiani D, et al. Infliximab treatment for steroid-refractory acute graft-versus-host disease. Haematologica. 2004;89(11):1352–9.PubMed
102.
Jacobsohn DA, Hallick J, Anders V, McMillan S, Morris L, Vogelsang GB. Infliximab for steroid-refractory acute GVHD: a case series. Am J Hematol. 2003;74(2):119–24.PubMed
103.
Rao K, Rao A, Karlsson H, Jagani M, Veys P, Amrolia PJ. Improved survival and preserved antiviral responses after combination therapy with daclizumab and infliximab in steroid-refractory graft-versus-host disease. J Pediatr Hematol Oncol. 2009;31(6):456–61.PubMed
104.
Greinix HT, Knobler RM, Worel N, et al. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica. 2006;91(3):405–8.PubMed
105.
Perfetti P, Carlier P, Strada P, et al. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD. Bone Marrow Transplant. 2008;42(9):609–17.PubMed
106.
Couriel DR, Hosing C, Saliba R, et al. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood. 2006;107(8):3074–80.PubMed
107.
Pidala J, Kim J, Perkins J, et al. Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease. Bone Marrow Transplant. 2010;45:91–9924.
108.
Furlong T, Martin P, Flowers ME, et al. Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant. 2009;44(11):739–48.PubMedCentralPubMed
109.
Benito AI, Furlong T, Martin PJ, et al. Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation. 2001;72(12):1924–9.PubMed
110.
Hoda D, Pidala J, Salgado-Vila N, et al. Sirolimus for treatment of steroid-refractory acute graft-versus-host disease. Bone Marrow Transplant. 2010;45(8):1347–51.PubMed
111.
Cutler C, Logan B, Nakamura R, et al. Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood. 2014;124(8):1372–7.PubMed
112.
Bolanos-Meade J, Jacobsohn DA, Margolis J, et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol. 2005;23(12):2661–8.PubMed
113.
Pidala J, Kim J, Roman-Diaz J, et al. Pentostatin as rescue therapy for glucocorticoid-refractory acute and chronic graft-versus-host disease. Ann Transplant. 2010;15(4):21–9.PubMed
114.
Dazzi F, Lopes L, Weng L. Mesenchymal stromal cells: a key player in innate tolerance? Immunology. 2012;137(3):206–13.PubMedCentralPubMed
115.
Ippoliti C, Neumann J. Octreotide in the management of diarrhea induced by graft versus host disease. Oncol Nurs Forum. 1998;25(5):873–8.PubMed
116.
Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75(3):555–62.PubMed
117.
Gratwohl A, Brand R, Apperley J, et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood. 2002;100(12):3877–86.PubMed
118.
Stewart BL, Storer B, Storek J, et al. Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004;104(12):3501–6.PubMed
119.
Wolff D, Gerbitz A, Ayuk F, et al. Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD. Biol Blood Marrow Transplant. 2010;16(12):1611–28.PubMed
120.
Herrera AF, Kim HT, Bindra B, et al. A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(11):1737–43.PubMed
121.
Martin PJ, Weisdorf D, Przepiorka D, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: vI. design of clinical trials working group report. Biol Blood Marrow Transplant. 2006;12(5):491–505.PubMed
122.
Cutler C, Miklos D, Kim HT, et al. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006;108(2):756–62.PubMedCentralPubMed
123.
Kharfan-Dabaja MA, Mhaskar AR, Djulbegovic B, Cutler C, Mohty M, Kumar A. Efficacy of rituximab in the setting of steroid-refractory chronic graft-versus-host disease: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2009;15(9):1005–13.PubMed
124.
Gutierrez-Aguirre CH, Cantu-Rodriguez OG, Borjas-Almaguer OD, et al. Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease. Haematologica. 2012;97(5):717–22.PubMedCentralPubMed
125.
van Dorp S, Pietersma F, Wolfl M, et al. Rituximab treatment before reduced-intensity conditioning transplantation associates with a decreased incidence of extensive chronic GVHD. Biol Blood Marrow Transplant. 2009;15(6):671–8.PubMed
126.
Arai S, Sahaf B, Narasimhan B, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012;119(25):6145–54.PubMedCentralPubMed
127.
Flowers ME, Apperley JF, van Besien K, et al. A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood. 2008;112(7):2667–74.PubMed
128.
Scarisbrick JJ, Taylor P, Holtick U, et al. UK consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol. 2008;158(4):659–78.PubMed
129.
Dignan FL, Greenblatt D, Cox M, et al. Efficacy of bimonthly extracorporeal photopheresis in refractory chronic mucocutaneous GVHD. Bone Marrow Transplant. 2012;47(6):824–30.PubMed
130.
Kuzmina Z, Greinix HT, Knobler R, et al. Proportions of immature CD19+CD2− B lymphocytes predict the response to extracorporeal photopheresis in patients with chronic graft-versus-host disease. Blood. 2009;114:744–6.PubMed
131.
Whittle R, Taylor PC. Circulating B-cell activating factor level predicts clinical response of chronic graft-versus-host disease to extracorporeal photopheresis. Blood. 2011;118(24):6446–9.PubMed
132.
Ghoreschi K, Thomas P, Penovici M, et al. PUVA-bath photochemotherapy and isotretinoin in sclerodermatous graft-versus-host disease. Eur J Dermatol. 2008;18(6):667–70.PubMed
133.
Svegliati S, Olivieri A, Campelli N, et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood. 2007;110(1):237–41.PubMed
134.
Olivieri A, Locatelli F, Zecca M, et al. Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood. 2009;114(3):709–18.PubMed
135.
Stadler M, Ahlborn R, Kamal H. Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host disease, vol. 114. United States: Blood; 2009. p. 3718–9 (author reply 3719–3720).
136.
Magro L, Mohty M, Catteau B, et al. Imatinib mesylate as salvage therapy for refractory sclerotic chronic graft-versus-host disease. Blood. 2009;114(3):719–22.PubMed
137.
Sanchez-Ortega I, Servitje O, Arnan M, et al. Dasatinib as salvage therapy for steroid refractory and imatinib resistant or intolerant sclerotic chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012;18(2):318–23.PubMed
138.
Koreth J, Antin JH. Current and future approaches for control of graft-versus-host disease. Expert Rev Hematol. 2008;1(1):111.PubMedCentralPubMed
139.
Lopez F, Parker P, Nademanee A, et al. Efficacy of mycophenolate mofetil in the treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11(4):307–13.PubMed
140.
Martin PJ, Storer BE, Rowley SD, et al. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood. 2009;113(21):5074–82.PubMedCentralPubMed
141.
Couriel DR, Saliba R, Escalon MP, et al. Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease. Br J Haematol. 2005;130(3):409–17.PubMed
142.
Jedlickova Z, Burlakova I, Bug G, Baurmann H, Schwerdtfeger R, Schleuning M. Therapy of sclerodermatous chronic graft-versus-host disease with mammalian target of rapamycin inhibitors. Biol Blood Marrow Transplant. 2011;17(5):657–63.PubMed
143.
Johnston LJ, Brown J, Shizuru JA, et al. Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11(1):47–55.PubMed
144.
Shin HJ, Baker J, Leveson-Gower DB, Smith AT, Sega EI, Negrin RS. Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+ CD25+ Foxp3+ regulatory T cells. United States: Blood; 2011. p. 2342–50.
145.
Peccatori J, Forcina A, Clerici D. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors, vol. 29. England: Leukemia; 2015. p. 396–405.
146.
Jacobsohn DA, Chen AR, Zahurak M, et al. Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol. 2007;25(27):4255–61.PubMed
147.
Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+) CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196(3):389–99.PubMedCentralPubMed
148.
Wolf D, von Lilienfeld-Toal M, Wolf AM, et al. Novel treatment concepts for graft-versus-host disease. Blood. 2012;119(1):16–25.PubMed
149.
Koreth J, Matsuoka K, Kim HT, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365(22):2055–66.PubMedCentralPubMed
150.
Wang Y, Xu LP, Liu DH, et al. First-line therapy for chronic graft-versus-host disease that includes low-dose methotrexate is associated with a high response rate. Biol Blood Marrow Transplant. 2009;15(4):505–11.PubMed
151.
Inagaki J, Nagatoshi Y, Hatano M, Isomura N, Sakiyama M, Okamura J. Low-dose MTX for the treatment of acute and chronic graft-versus-host disease in children. Bone Marrow Transplant. 2008;41(6):571–7.PubMed
152.
Huang XJ, Jiang Q, Chen H, et al. Low-dose methotrexate for the treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;36(4):343–8.PubMed
153.
Blanco B, Sanchez-Abarca LI, Caballero-Velazquez T, Santamaria C, Inoges S, Perez-Simon JA. Depletion of alloreactive T-cells in vitro using the proteasome inhibitor bortezomib preserves the immune response against pathogens. Leuk Res. 2011;35(10):1412–5.PubMed
154.
El-Cheikh J, Michallet M, Nagler A, et al. High response rate and improved graft-versus-host disease following bortezomib as salvage therapy after reduced intensity conditioning allogeneic stem cell transplantation for multiple myeloma. Haematologica. 2008;93(3):455–8.PubMed
155.
Koreth J, Stevenson KE, Kim HT, et al. Bortezomib-based graft-versus-host disease prophylaxis in HLA-mismatched unrelated donor transplantation. J Clin Oncol. 2012;30(26):3202–8.PubMedCentralPubMed
156.
Vogelsang GB, Farmer ER, Hess AD, et al. Thalidomide for the treatment of chronic graft-versus-host disease. N Engl J Med. 1992;326(16):1055–8.PubMed
157.
Koc S, Leisenring W, Flowers ME, et al. Thalidomide for treatment of patients with chronic graft-versus-host disease. Blood. 2000;96(12):3995–6.PubMed
158.
Cowen EW, Nguyen JC, Miller DD, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31–7.PubMedCentralPubMed
159.
Rocha EM, Pelegrino FS, de Paiva CS, Vigorito AC, de Souza CA. GVHD dry eyes treated with autologous serum tears. Bone Marrow Transplant. 2000;25(10):1101–3.PubMed
160.
Yoshihara S, Yanik G, Cooke KR, Mineishi S. Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13(7):749–59.PubMed
161.
Chen X, Das R, Komorowski R, et al. Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease. Blood. 2009;114(4):891–900.PubMedCentralPubMed
162.
Tawara I, Koyama M, Liu C, et al. Interleukin-6 modulates graft-versus-host responses after experimental allogeneic bone marrow transplantation. Clin Cancer Res. 2011;17(1):77–88.PubMedCentralPubMed
163.
Drobyski WR, Pasquini M, Kovatovic K, et al. Tocilizumab for the treatment of steroid refractory graft-versus-host disease. Biol Blood Marrow Transplant. 2011;17(12):1862–8.PubMedCentralPubMed
164.
165.
Reshef R, Luger SM, Hexner EO, et al. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med. 2012;367(2):135–45.PubMedCentralPubMed
166.
Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117(14):3921–8.PubMed
167.
Al-Homsi AS, Roy TS, Cole K, Feng Y, Duffner U. Post-Transplant High-Dose Cyclophosphamide for the Prevention of Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2014;21:604–11.PubMed
168.
Zhou X, Di Stasi A, Tey SK, et al. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase nine safety transgene. Blood. 2014;123(25):3895–905.PubMed
169.
Dubovsky JA, Flynn R, Du J, et al. Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. J Clin Invest. 2014;124(11):4867–76.PubMedCentralPubMed
Metadata
Title
State-of-the-art acute and chronic GVHD treatment
Authors
Muhammad Omer Jamil
Shin Mineishi
Publication date
01-05-2015
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2015
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-015-1785-1

Other articles of this Issue 5/2015

International Journal of Hematology 5/2015 Go to the issue

Progress in Hematology

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

Progress in Hematology

Intestinal microbiota-related effects on graft-versus-host disease

Case Report

A case of clonally distinct relapse of Burkitt lymphoma 9 years after complete remission

Images in Hematology

Disappearance of double minute chromosomes with MYC amplification in relapsed acute myeloid leukemia after stem cell transplantation

Progress in Hematology

Recent topics in graft-versus-host disease: from the perspectives of pathogenesis and treatment

Original Article

Clinical significance of nontuberculous mycobacteria from respiratory specimens in stem cell transplantation recipients
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits