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Identical-Twin Bone Marrow Transplants for Leukemia

Robert Peter Gale, MD, PhD; Mary M. Horowitz, MD, MS; Robert C. Ash, MD; Richard E. Champlin, MD; John M. Goldman, MD; Alfred A. Rimm, PhD; Olle Ringden, MD; Judith A. Veum Stone, MS; and Mortimer M. Bortin, MD
[+] Article and Author Information

From the International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, Wisconsin; Salick Health Care, Inc., Los Angeles, California; Methodist Hospital Cancer Center, Indianapolis, Indiana; M.D. Anderson Cancer Center, Houston, Texas; Royal Postgraduate Medical School, London, United Kingdom; Case Western University School of Medicine, Cleveland, Ohio; Huddinge University Hospital, Huddinge, Sweden. Requests for Reprints: Mary M. Horowitz, MD, International Bone Marrow Transplant Registry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 52226. Acknowledgments: The authors thank Ms. D'Etta Waldoch Koser and Sharon K. Nell for help with data management and analysis; and Susan J. Hogg, Dottie J. Jacobson, and Linda J. Hoffman for preparation of the manuscript. Grant Support: In part by Public Health Service grant PO1-CA-40053 from the National Cancer Institute and the National Institute of Allergy and Infectious Diseases of the U.S. Department of Health and Human Services; and grants from Alpha Therapeutic Corporation; Amgen, Inc.; Armour Pharmaceutical Company; Astra Pharmaceutical Products, Inc.; Lynde and Harry Bradley Foundation; Bristol-Myers Oncology; Burroughs-Wellcome Company; Charles E. Culpeper Foundation; Eleanor Naylor Dana Charitable Trust; Eppley Foundation for Research; Hoechst-Roussel Pharmaceuticals; Immunex Corporation; Kettering Family Foundation; Robert J. and Helen C. Kleberg Foundation; Eli Lilly and Company Foundation; Samuel Roberts Noble Foundation; Ortho Biotech Corporation; Elsa U. Pardee Foundation; Jane and Lloyd Pettit Foundation; RGK Foundation; Roche Laboratories; Roerig Division of Pfizer Pharmaceuticals; Sandoz Research Institute; Walter Schroeder Foundation; Stackner Family Foundation; Starr Foundation; Joan and Jack Stein Charities; Swiss Cancer League; and Wyeth-Ayerst Research.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;120(8):646-652. doi:10.7326/0003-4819-120-8-199404150-00004
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Objective: To compare outcomes of identical-twin with HLA-identical sibling bone marrow transplants for leukemia.

Design: Matched-pair analysis comparing relapse, treatment-related mortality, and leukemia-free survival in cohorts matched for disease and variables correlated with transplant outcome, with and without adjustment for graft-versus-host disease.

Setting: 163 institutions worldwide between 1978 and 1990, reporting to the International Bone Marrow Transplant Registry.

Participants: 103 identical-twin transplants: 24 for acute lymphoblastic leukemia (ALL) in first remission, 45 for acute myelogenous leukemia (AML) in first remission, and 34 for chronic myelogenous leukemia (CML) in first chronic phase. Results were compared with those in 1030 concurrent HLA-identical sibling transplants matched for prognostic factors.

Results: Three-year probabilities of relapse after identical-twin compared with HLA-identical sibling transplants were as follows: ALL, 36% (95% CI, 17% to 55%) compared with 26% (CI, 20% to 32%); AML, 52% (CI, 37% to 67%) compared with 16% (CI, 12% to 20%); and CML, 40% (CI, 23% to 57%) compared with 7% (CI, 4% to 10%). Increased relapse risks in AML and CML persisted after adjusting for graft-versus-host disease (relative risk, 3.1 [CI, 1.9 to 5.1] and 5.5 [CI, 2.8 to 11.0], respectively). Although twins had less treatment-related mortality than HLA-identical siblings, leukemia-free survival was similar. Three-year leukemia-free survival probabilities after twin compared with HLA-identical sibling transplants were as follows: ALL, 57% (CI, 37% to 77%) compared with 58% (CI, 52% to 64%); AML, 42% (CI, 27% to 57%) compared with 55% (CI, 50% to 60%); and CML, 59% (CI, 42% to 76%) compared with 61% (CI, 56% to 66%).

Conclusions: Identical-twin transplants in AML and CML are associated with increased relapse risk compared with HLA-identical sibling transplants. A similar trend was observed in ALL but was not statistically significant. Increased relapse in twin transplants is not explained by lack of graft-versus-host disease. Leukemia-free survival after twin and HLA-identical sibling transplants is similar because increased relapse in twins is offset by decreased treatment-related mortality.

Figures

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Figure 1.
Outcome of transplants for acute lymphoblastic leukemia.topbottom

Actuarial probability of relapse ( ) and leukemia-free survival ( ) after identical-twin and HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia in first remission. Numbers in parentheses are numbers at risk (alive in continuous complete remission) at indicated intervals.

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Grahic Jump Location
Figure 2.
Outcome of transplants for acute myelogenous leukemia.topbottom

Actuarial probability of relapse ( ) and leukemia-free survival ( ) after identical-twin and HLA-identical sibling bone marrow transplants for acute myelogenous leukemia in first remission. Numbers in parentheses are numbers at risk (alive in continuous complete remission) at indicated intervals.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Outcome of transplants for chronic myelogenous leukemia.topbottom

Actuarial probability of relapse ( ) and leukemia-free survival ( ) after identical-twin and HLA-identical sibling bone marrow transplantation for chronic myelogenous leukemia in chronic phase. Numbers in parentheses are numbers at risk (alive in continuous complete remission) at indicated intervals.

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