Increasing Incidence of Chronic Graft-versus-host Disease in Allogeneic Transplantation: a Report from the Center for International Blood and Marrow Transplant Research

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

Citing Articles

Vovk N, Urek M, Cankar K, Nemeth L Healthcare (Basel). 2025; 13(5).

PMID: 40077124 PMC: 11899322. DOI: 10.3390/healthcare13050561.

Belumosudil for the treatment of chronic graft-versus-host disease: a single center real-world experience.

Modi B, Ngo D, Chen J, Yang D, Shan H, Sandhu K Bone Marrow Transplant. 2025; .

PMID: 39905130 DOI: 10.1038/s41409-024-02498-7.

Clonal GZMKCD8 T cells are identified as a hallmark of the pathogenesis of cGVHD-induced bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation.

Gao Y, Liu R, Shi J, Shan W, Zhou H, Chen Z EBioMedicine. 2024; 112:105535.

PMID: 39740295 PMC: 11750515. DOI: 10.1016/j.ebiom.2024.105535.

Semimechanistic Population PK/PD Modeling of Axatilimab in Healthy Participants and Patients With Solid Tumors or Chronic Graft-Versus-Host Disease.

Yang Y, Sokolov V, Volkova A, Liu X, Leon C, Kosinsky Y Clin Pharmacol Ther. 2024; 117(3):704-715.

PMID: 39704205 PMC: 11835428. DOI: 10.1002/cpt.3503.

Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease.

Kambara Y, Fujiwara H, Yamamoto A, Gotoh K, Tsuji S, Kunihiro M Blood. 2024; 145(8):881-896.

PMID: 39693612 PMC: 11867138. DOI: 10.1182/blood.2024024540.

References

Cutler C, Giri S, Jeyapalan S, Paniagua D, Viswanathan A, Antin J . Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol. 2001; 19(16):3685-91. DOI: 10.1200/JCO.2001.19.16.3685. View

Kollman C, HOWE C, Anasetti C, Antin J, Davies S, Filipovich A . Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001; 98(7):2043-51. DOI: 10.1182/blood.v98.7.2043. View

Lee S, Klein J, Barrett A, Ringden O, Antin J, Cahn J . Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002; 100(2):406-14. DOI: 10.1182/blood.v100.2.406. View

Luger S, Sacks N . Bone marrow transplantation for myelodysplastic syndrome--who? when? and which?. Bone Marrow Transplant. 2002; 30(4):199-206. DOI: 10.1038/sj.bmt.1703610. View

Ringden O, Labopin M, Bacigalupo A, Arcese W, Schaefer U, Willemze R . Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia. J Clin Oncol. 2002; 20(24):4655-64. DOI: 10.1200/JCO.2002.12.049. View

Lee S, Vogelsang G, Flowers M . Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003; 9(4):215-33. DOI: 10.1053/bbmt.2003.50026. View

Couriel D, Saliba R, Giralt S, Khouri I, Andersson B, de Lima M . 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. DOI: 10.1016/j.bbmt.2003.10.006. View

Shulman H, Sullivan K, Weiden P, McDonald G, Striker G, Sale G . Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980; 69(2):204-17. DOI: 10.1016/0002-9343(80)90380-0. View

Ringden O, Paulin T, Lonnqvist B, Nilsson B . An analysis of factors predisposing to chronic graft-versus-host disease. Exp Hematol. 1985; 13(10):1062-7. View

10.

Carlens S, Ringden O, Remberger M, Lonnqvist B, Hagglund H, Klaesson S . Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant. 1998; 22(8):755-61. DOI: 10.1038/sj.bmt.1701423. View

11.

Gooley T, Leisenring W, Crowley J, Storer B . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999; 18(6):695-706. DOI: 10.1002/(sici)1097-0258(19990330)18:6<695::aid-sim60>3.0.co;2-o. View

12.

Socie G, Stone J, Wingard J, Weisdorf D, Henslee-Downey P, Bredeson C . Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med. 1999; 341(1):14-21. DOI: 10.1056/NEJM199907013410103. View

13.

Stewart B, Storer B, Storek J, Deeg H, Storb R, Hansen J . Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004; 104(12):3501-6. DOI: 10.1182/blood-2004-01-0200. View

14.

Remberger M, Beelen D, Fauser A, Basara N, Basu O, Ringden O . Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood. 2004; 105(2):548-51. DOI: 10.1182/blood-2004-03-1000. View

15.

Klein J, Andersen P . Regression modeling of competing risks data based on pseudovalues of the cumulative incidence function. Biometrics. 2005; 61(1):223-9. DOI: 10.1111/j.0006-341X.2005.031209.x. View

16.

Aoudjhane M, Labopin M, Gorin N, Shimoni A, Ruutu T, Kolb H . Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective.... Leukemia. 2005; 19(12):2304-12. DOI: 10.1038/sj.leu.2403967. View

17.

Filipovich A, Weisdorf D, Pavletic S, Socie G, Wingard J, Lee S . National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12):945-56. DOI: 10.1016/j.bbmt.2005.09.004. View

18.

Martin P, Weisdorf D, Przepiorka D, Hirschfeld S, Farrell A, Rizzo J . 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. DOI: 10.1016/j.bbmt.2006.03.004. View

19.

Subramaniam D, Fowler D, Pavletic S . Chronic graft-versus-host disease in the era of reduced-intensity conditioning. Leukemia. 2007; 21(5):853-9. DOI: 10.1038/sj.leu.2404642. View

20.

Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C . Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transplant. 2008; 14(7):748-58. PMC: 2668157. DOI: 10.1016/j.bbmt.2008.04.003. View