Results of Allogeneic Bone Marrow Transplants for Leukemia Using Donors Other Than HLA-Identical Siblings By Richard Szydlo, John M. Goldman, John P. Klein, Robert Peter Gale, Robert C. Ash, Fritz H. Bach, Benjamin A. Bradley, James T. Casper, Neal Flomenberg, James L. Gajewski, Eliane Gluckman, P. Jean Henslee-Downey, Jill M. Hows, Niels Jacobsen, Hans-Jochem Kolb, Bob Lowenberg, Tohru Masaoka, Philip A. Rowlings, Paul M. Sondel, Dirk W. van Bekkum, Jon J. van Rood, Marcus R. Vowels, Mei-Jie Zhang, and Mary M. Horowitz Purpose: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA- matched and mismatched unrelated donors. Patients: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leu- kemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR anti- gen (n = 108). HLA typing was performed using serologic techniques. Results: Transplant-related mortality was significantly higerafter alternative donor transplants than after HLA- identical sibling transplants. Among patients with early leu- kemia (CML in chronic phase or acute leukemia in first re- mission), 3-year transplant-elated mortality (± SE) was 21% + 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor trans- plants studied. Among patients with early leukemia, rela- tive risks of treatment failure (inverse of leukemia-free sur- vival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-anti- gen-mismatched related donors, 3.79 (P < .0001) with 2- HLA-antigen-mismatched related donors, 2.11 (P< .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with I -HLA-antigen-mismatched unrelated donors. For pa- tients with more advanced leukemia, differences in treat- ment failure were less striking: 1 -HLA-antigen-mismatched relatives, 1.22 (P = not significant [NSI); 2-HLA-antigen- mismatched relatives, 1.81 (P < .0001); HLA-matched un- related donors, 1.39 (P = .002); and 1-HLA-antigen-mis- matched unrelated donors, 1.63 (P = .002). Conclusion: Although transplants from alternative do- nors are effective in some patients with leukemia, treat- ment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor- recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This dif- ference is less in advanced leukemia. J Clin Oncol 15:1767-1777. 1997 by American So- ciety of Clinical Oncology. From the International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, WI (JPK, RCA, PAR, MJZ, MMH); Royal Postgraduate Medical School, Ham- mersmith Hospital, London, United Kingdom (RS, JMG); Division of Bone Marrow and Stem Cell Transplantation, Salick Health Care, Inc, Los Angeles, CA (RPG); New England Deaconess Hospital, Harvard Medical School, Boston, MA (FHB); Department of Trans- plantation, University of Bristol, Bristol, United Kingdom (BAB, JMH); Department of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI (JTC); Thomas Jefferson Uni- versity, Philadelphia, PA (NF); MD Anderson Cancer Center, Uni- versity of Texas, Houston, TX (JLG); Hdpital Saint-Louis, Service d'Hematologie, Paris, France (EG); University of South Carolina, Columbia, SC (PJH-D); Department of Haematology, Rigshospi- talet, Copenhagen, Denmark (NJ); Medizinische Klinik III, Universi- tat Muenchen, Munich, Germany (H-JK); The Dr. Daniel den Hoed Cancer Center, Rotterdam, the Netherlands (BL); 5th Internal Medi- cine Center forAdult Diseases, Osaka, Japan (TM); Clinical Cancer Center, University of Wisconsin, Madison, WI (PMS); Radiobiologi- cal Institute, Rijswijk, the Netherlands (DWvB); University Hospital, Leiden, the Netherlands (JJvR); and Sydney Children's Hospital, Randwick, Australia (MRV). Submitted June 24, 1996; accepted February 11, 1997. Supported by Public Health Service grant no. P01-CA-40053 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung and Blood Institute, of the US Department of Health and Human Services, Bethesda, MD; and grants from Alpha Therapeutic Corp, Los Angeles, CA; Amgen, Inc, Thousand Oaks, CA; Astra Pharmaceuti- cal, Westborough, MA; Baxter Healthcare Corp, Deerfield, IL; Bayer Corp, West Haven, CT; Biogen, Cambridge, MA; Blue Cross and Blue Shield Association, Chicago, IL; Lynde and Harry Bradley Foundation, Milwaukee, WI; Bristol-Myers Squibb Company, Princeton, NJ; Frank G. Brotz Family Foundation, Sheboygan, WI; Cancer Center, Medical College of Wisconsin, Milwaukee, WI; Cell- Pro, Inc, Bothell, WA; Centeon, King of Prussia, PA; Center for Advanced Studies in Leukemia, Santa Monica, CA; Charles E. Cul- peper Foundation, Stamford. CT; Eleanor Naylor Dana Charitable Trust, New York, NY; Eppley Foundation for Research, New York, NY; Genentech, Inc, San Francisco, CA; Glaxo Wellcome Company, Research Triangle Park, CA; Hoechst Marion Roussel, Inc, Kansas City, MO; Immunex Corp, Seattle, WA; Janssen Pharmaceutica, Titusville, NJ; Kettering Family Foundation, Denver, CO; Kirin Brewery Company, Tokyo, Japan; Robert J. Kleberg, Jr and Helen C. Kleberg Foundation, San Antonio, TX; Herbert H. Kohl Charities, Inc, Milwaukee, WI; Eli Lilly Company Foundation, Indianapolis, IN; Nada and Herbert P. Mahler Charities, Mequon, WI; Milstein Family Foundation, New York, NY; Milwaukee Foundation /Elsa Schoeneich Research Fund, Milwaukee, WI; Samuel Roberts Noble Journal of Clinical Oncology, Vol 15, No 5 (May), 1997: pp 1767-1777 1767 Copyright © 1997 by the American Society of Clinical Oncology. All rights reserved. Downloaded from www.jco.org at UNIV WISCONSIN MADISON on July 12, 2005 .