Significance of Ethnicity in the Risk of Acute Graft-versus-host Disease and Leukemia Relapse After Unrelated Donor Hematopoietic Stem Cell Transplantation

Overview

Journal Biol Blood Marrow Transplant

Date 2013 Jun 11

PMID 23747601

Citations 30

Authors

Yasuo Morishima

Takakazu Kawase

Mari Malkki

Satoko Morishima

Stephen Spellman

Koichi Kashiwase

Shunichi Kato

Anne Cesbron

Jean-Marie Tiercy

David Senitzer

Andrea Velardi

Effie W Petersdorf

Affiliations

Soon will be listed here.

Abstract

The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient-donor pairs from the International Histocompatibility Working Group in HCT met the following 3 criteria: (1) HLA-A, -B, -C, -DRB1, and -DQB1 allele matched donor, (2) diagnosis of leukemia, and (3) non-T cell depleted GVHD prophylaxis. Posttransplantation risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, white, African American, Hispanic, and Native American patients that underwent transplantation from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II to IV and 15.3% grades III to IV; non-Japanese Asian patients: 42.1% grades II to IV and 15.7% grades III to IV) compared with white patients (56.5% grades II to IV and 22.6% grades III to IV) (P < .001). The hazard ratio of acute GVHD for white patients was significantly higher than for Japanese patients. Unexpectedly, the hazard ratio of leukemia relapse in white patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background.

Citing Articles

A randomized controlled trial of conventional GVHD prophylaxis with or without teprenone for the prevention of severe acute GVHD.

Kitamura W, Fujii K, Tsuge M, Mitsuhashi T, Kobayashi H, Kamoi C Ann Hematol. 2025; .

PMID: 39994018 DOI: 10.1007/s00277-025-06269-2.

Racial, ethnic, and socioeconomic diversity and outcomes of patients with graft-versus-host disease: a CIBMTR analysis.

Farhadfar N, Rashid N, Chen K, DeVos J, Wang T, Ballen K Blood Adv. 2024; 8(18):4963-4976.

PMID: 38776400 PMC: 11496972. DOI: 10.1182/bloodadvances.2024013074.

Acute graft-versus-host disease.

Malard F, Holler E, Sandmaier B, Huang H, Mohty M Nat Rev Dis Primers. 2023; 9(1):27.

PMID: 37291149 DOI: 10.1038/s41572-023-00438-1.

Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease.

Kate A, Singh S, Das A, Basu S Indian J Ophthalmol. 2023; 71(4):1538-1544.

PMID: 37026297 PMC: 10276705. DOI: 10.4103/IJO.IJO_2820_22.

Race and Survival in Unrelated Hematopoietic Cell Transplantation.

Morishima Y, Morishima S, Stevenson P, Kodera Y, Horowitz M, McKallor C Transplant Cell Ther. 2022; 28(7):357.e1-357.e6.

PMID: 35405366 PMC: 9387555. DOI: 10.1016/j.jtct.2022.03.026.

References

Lee S, Klein J, Haagenson M, Baxter-Lowe L, Confer D, Eapen M . High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007; 110(13):4576-83. DOI: 10.1182/blood-2007-06-097386. View

Goulmy E . Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev. 1997; 157:125-40. DOI: 10.1111/j.1600-065x.1997.tb00978.x. View

Maiers M, Gragert L, Klitz W . High-resolution HLA alleles and haplotypes in the United States population. Hum Immunol. 2007; 68(9):779-88. DOI: 10.1016/j.humimm.2007.04.005. View

Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K . The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002; 99(11):4200-6. DOI: 10.1182/blood.v99.11.4200. View

Morishima S, Ogawa S, Matsubara A, Kawase T, Nannya Y, Kashiwase K . Impact of highly conserved HLA haplotype on acute graft-versus-host disease. Blood. 2010; 115(23):4664-70. DOI: 10.1182/blood-2009-10-251157. View

Fleischhauer K, Shaw B, Gooley T, Malkki M, Bardy P, Bignon J . Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol. 2012; 13(4):366-74. PMC: 3813000. DOI: 10.1016/S1470-2045(12)70004-9. View

Spellman S, Eapen M, Logan B, Mueller C, Rubinstein P, Setterholm M . A perspective on the selection of unrelated donors and cord blood units for transplantation. Blood. 2012; 120(2):259-65. PMC: 3398760. DOI: 10.1182/blood-2012-03-379032. View

Petersdorf E, Bardy P, Cambon-Thomsen A, Goulmy E, Hansen J, Schwarer A . 14thInternational HLA and Immunogenetics Workshop: report on hematopoietic cell transplantation. Tissue Antigens. 2007; 69 Suppl 1:17-24. DOI: 10.1111/j.1399-0039.2006.759_1.x. View

Penack O, Holler E, van den Brink M . Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood. 2010; 115(10):1865-72. DOI: 10.1182/blood-2009-09-242784. View

10.

Morishima Y, Kawase T, Malkki M, Petersdorf E . Effect of HLA-A2 allele disparity on clinical outcome in hematopoietic cell transplantation from unrelated donors. Tissue Antigens. 2007; 69 Suppl 1:31-5. DOI: 10.1111/j.1399-0039.2006.759_3.x. View

11.

Baschal E, Aly T, Jasinski J, Steck A, Noble J, Erlich H . Defining multiple common "completely" conserved major histocompatibility complex SNP haplotypes. Clin Immunol. 2009; 132(2):203-14. PMC: 3740523. DOI: 10.1016/j.clim.2009.03.530. View

12.

Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H . Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med. 1998; 339(17):1177-85. DOI: 10.1056/NEJM199810223391701. View

13.

Abecasis G, Altshuler D, Auton A, Brooks L, Durbin R, Gibbs R . A map of human genome variation from population-scale sequencing. Nature. 2010; 467(7319):1061-73. PMC: 3042601. DOI: 10.1038/nature09534. View

14.

Petersdorf E . Immunogenomics of unrelated hematopoietic cell transplantation. Curr Opin Immunol. 2006; 18(5):559-64. DOI: 10.1016/j.coi.2006.07.003. View

15.

Kawase T, Matsuo K, Kashiwase K, Inoko H, Saji H, Ogawa S . HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood. 2008; 113(12):2851-8. DOI: 10.1182/blood-2008-08-171934. View

16.

Mielcarek M, Gooley T, Martin P, Chauncey T, Young B, Storb R . Effects of race on survival after stem cell transplantation. Biol Blood Marrow Transplant. 2005; 11(3):231-9. DOI: 10.1016/j.bbmt.2004.12.327. View

17.

Lin M, Storer B, Martin P, Tseng L, Gooley T, Chen P . 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. DOI: 10.1056/NEJMoa022060. View

18.

Hansen J, Petersdorf E, Lin M, Wang S, Chien J, Storer B . Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes. Immunol Res. 2007; 41(1):56-78. DOI: 10.1007/s12026-007-0043-x. View

19.

Petersdorf E, Gooley T, Anasetti C, Martin P, Smith A, Mickelson E . Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood. 1998; 92(10):3515-20. View

20.

Petersdorf E, Malkki M, Gooley T, Spellman S, Haagenson M, Horowitz M . MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation. Sci Transl Med. 2012; 4(144):144ra101. PMC: 3633562. DOI: 10.1126/scitranslmed.3003974. View