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HLA-Identical Sibling Bone Marrow Transplantation in Younger Patients with Chronic Lymphocytic Leukemia

Mauricette Michallet, MD; Eric Archimbaud, MD; Giuseppe Bandini, MD; Philip A. Rowlings, MBBS; H. Joachim Deeg, MD; Gosta Gahrton, MD; Emilio Montserrat, MD; Ciril Rozman, MD; Alois Gratwohl, MD; Robert Peter Gale, MD, PhD, European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry
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From Edouard Herriot Hospital, Lyon, France; San Orsola Hospital, Bologna, Italy; Medical College of Wisconsin, Milwaukee, Wisconsin; Fred Hutchinson Cancer Research Center, Seattle, Washington; Huddinge Hospital and Karolinska Institute, Huddinge, Sweden; Clinic I Provincial Hospital, Barcelona, Spain; University Hospital, Basel, Switzerland; and Salick Health Care, Inc., Los Angeles, California. Acknowledgments: The authors thank Lisa J. Schneider for assistance in preparing the manuscript and Sandy Kempin, MD, for his review and comments. Grant Support: By Public Health Service Grant PO1-CA-40053 from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Heart, Lung, and Blood Institute; and grants from Alpha Therapeutic Corporation, Armour Pharmaceutical Company, Astra Pharmaceutical, Baxter Healthcare Corporation, Biogen, Lynde and Harry Bradley Foundation, Bristol-Myers Squibb Company, Frank G. Brotz Family Foundation, Burroughs-Wellcome Company, Cancer Center of the Medical College of Wisconsin, Center for Advanced Studies in Leukemia, Charles E. Culpeper Foundation, Eleanor Naylor Dana Charitable Trust, Eppley Foundation for Research, Immunex Corporation, Kettering Family Foundation, Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, Eli Lilly Company Foundation, Nada and Herbert P. Mahler Charities, Marion Merrell Dow, Inc., Milstein Family Foundation, Milwaukee Foundation/Elsa Schoeneich Research Fund, Samuel Roberts Noble Foundation, Ortho Biotech Corporation, John Oster Family Foundation, Elsa U. Pardee Foundation, Jane and Lloyd Pettit Foundation, Pharmacia, RGK Foundation, Roerig/Pfizer Pharmaceuticals, Sandoz Pharmaceuticals, Walter Schroeder Foundation, Stackner Family Foundation, Starr Foundation, Joan and Jack Stein Charities, and Wyeth-Ayerst Laboratories. Requests for Reprints: Philip A. Rowlings, MD, International Bone Marrow Transplant Registry, Medical College of Wisconsin, 8701 Watertown Plank Road, PO Box 26509, Milwaukee, WI 53226. Current Author Addresses: Dr. Michallet: Hopitaux de lyon, Hopital Edouard herriot, Place d'Arsonaval, Pavillion E, 69437 Lyon Cedex 03, France.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(3):311-315. doi:10.7326/0003-4819-124-3-199602010-00005
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Objective: To characterize in detail the outcomes of HLA-identical sibling bone marrow transplantation for chronic lymphocytic leukemia (CLL) in patients younger than 60 years of age.

Design: Retrospective cohort study.

Setting: 30 centers for bone marrow transplantation worldwide, which reported data on outcome of HLA-identical sibling bone marrow transplantation for CLL to the European Group for Blood and Marrow Transplantation or the International Bone Marrow Transplant Registry between 1984 and 1992.

Patients: 54 patients diagnosed with CLL (median age, 41 years; range, 21 to 58 years). The median interval from diagnosis to transplantation was 37 months (range, 5 to 130 months). At the time of transplantation, 3 patients were at Rai stage 0; 10 were at stage 1; 10 were at stage 2; 7 were at stage 3; and 22 were at stage 4.

Intervention: Transplant regimens varied. Most patients received high-dose cyclophosphamide and total body irradiation, followed by infusion of bone marrow from an HLA-identical sibling. After transplantation, immune suppression with cyclosporine or methotrexate or both was generally used to prevent graft-versus-host disease.

Measurements: The primary outcome was survival. We also studied hematologic remission, defined as normalization of the leukocyte count, hemoglobin level, and platelet count, and absence of lymphadenopathy and splenomegaly.

Results: 38 patients (70%) achieved hematologic remission. Twenty-four (44%) remain alive a median of 27 months (range, 5 to 80 months) after transplantation. Three-year survival probability was 46% (95% CI, 32% to 60%). Three patients who received transplants at Rai stage 0 remain alive 21, 32, and 45 months after transplantation. Three-year survival probabilities were as follows: 68% (CI, 38% to 98%) in 10 patients who received transplants at Rai stage 1, 30% (CI, 2% to 58%) in 10 patients who received transplants at Rai stage 2, 57% (CI, 21% to 93%) in 7 patients who received transplants at Rai stage 3, and 34% (CI, 12% to 56%) in 22 patients who received transplants at Rai stage 4 CLL. Five patients (9%) died of progressive leukemia and 25 (46%) of treatment-related complications.

Conclusions: Bone marrow transplants from HLA-identical siblings can result in hematologic remission and survival in persons with CLL, but it is uncertain how these results compare with those of conventional therapies.

*For additional contributors and participating centers, see the Appendix.


Grahic Jump Location
Figure 1.
Probability of survival among 54 patients after HLA-identical sibling bone marrow transplantation for chronic lymphocytic leukemia.

Numbers in parentheses indicate patients at risk for dying at each time point.

Grahic Jump Location




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