The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation

Author:

Ringdén Olle1,Pavletic Steven Z.2,Anasetti Claudio3,Barrett A. John2,Wang Tao4,Wang Dan4,Antin Joseph H.5,Di Bartolomeo Paolo6,Bolwell Brian J.7,Bredeson Christopher4,Cairo Mitchell S.8,Gale Robert P.9,Gupta Vikas10,Hahn Theresa11,Hale Gregory A.12,Halter Jorg13,Jagasia Madan14,Litzow Mark R.15,Locatelli Franco16,Marks David I.17,McCarthy Philip L.11,Cowan Morton J.18,Petersdorf Effie W.19,Russell James A.20,Schiller Gary J.21,Schouten Harry22,Spellman Stephen4,Verdonck Leo F.23,Wingard John R.24,Horowitz Mary M.4,Arora Mukta25

Affiliation:

1. Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden;

2. Experimental Transplantation and Immunology Branch, National Institutes of Health, Bethesda, MD;

3. BMT Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;

4. Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee;

5. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA;

6. Department of Haematology, Ospedale Civile, Pescara, Italy;

7. Cleveland Clinic Foundation, OH;

8. Pediatrics, Columbia University Medical Center, New York, NY;

9. Center for Advanced Studies in Leukemia, Los Angeles, CA;

10. BMT Program, Princess Margaret Hospital, Toronto, ON;

11. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY;

12. St Jude Children's Research Hospital, Memphis, TN;

13. University Hospital Basel, Basel, Switzerland;

14. Hematology/Stem Cell Transplantation, Vanderbilt University Medical Center, Nashville, TN;

15. Mayo Clinic, Rochester, MN;

16. Pediatric Hematology-Oncology, IRCCS Policlinico San Matteo, Pavia, Italy;

17. Adult BMT Unit, United Bristol Healthcare Trust, Bristol, United Kingdom;

18. BMT Division, University of California, San Francisco (UCSF) Children's Hospital;

19. Fred Hutchinson Cancer Research Center, Seattle, WA;

20. Department of Medicine, Tom Baker Cancer Center, Calgary, AB;

21. University of California at Los Angeles (UCLA) School of Medicine;

22. University Hospital Maastricht, Maastricht, The Netherlands;

23. University Hospital Utrecht, Utrecht, The Netherlands;

24. University of Florida, Health Science Center (HSC) College of Medicine, Gainesville; and

25. University of Minnesota, Minneapolis

Abstract

AbstractDo some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]–matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference38 articles.

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2. Graft-versus-leukemia effect in allogeneic marrow transplant recipients with acute leukemia is maintained using cyclosporin A combined with methotrexate as prophylaxis. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.;Ringden;Bone Marrow Transplant,1996

3. Graft-versus-leukemia.;Truitt,1996

4. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation.;Weiden;N Engl J Med,1981

5. Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than syngeneic marrow transplantation.;Fefer,1987

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