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Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia Using Sibling and Volunteer Unrelated Donors: A Comparison of Complications in the First 2 Years

David I. Marks, PhD; Jonathan O. Cullis, MB; Katherine N. Ward, PhD; Sandra Lacey, MB; Richard Szydlo, PhD; Timothy P. Hughes, MD; Anthony P. Schwarer, MB; Edwin Lutz, MD; A. John Barrett, MD; Jill M. Hows, MD; J. Richard Batchelor, MD; and John M. Goldman, MD
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From Hammersmith Hospital, London, United Kingdom. Requests for Reprints: John M. Goldman, DM, LRF Centre for Adult Leukaemia, Haematology Department, Royal Postgraduate Medical School, DuCane Rd, London W12, ONN, United Kingdom. Acknowledgments: The authors thank Paul Brookes, Jan Green, and Ed Kaminski for performing the tissue typing and analysis of cytotoxic T-lymphocyte precursor frequencies; Linda Casey, Susan Cleaver and Dr. Dick Goffin for donor searching, and Julie Bungey and Andrew Chase for performing the cytogenetic analyses; and Drs. H. Waldman and G. Hale, Department of Pathology, Cambridge University, Cambridge, United Kingdom, for producing and supplying all monoclonal antibodies of the Campath series used in this study. Grant Support: Drs. Marks, Cullis, Szydlo, Hughes, and Schwarer were supported by the Leukaemia Research Fund, United Kingdom.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(3):207-214. doi:10.7326/0003-4819-119-3-199308010-00005
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Objective: To compare the short- and medium-term complications (particularly infection) of bone marrow transplantation for chronic myeloid leukemia in patients with HLA-identical sibling donors or volunteer unrelated donors.

Design: Retrospective review of two cohorts of patients.

Setting: Tertiary referral center.

Patients: One hundred three patients with chronic myeloid leukemia in first chronic phase.

Intervention: Patients were treated with bone marrow transplantation using marrow from HLA-identical siblings (n = 57) and volunteer donors (n = 46).

Main Results: In total, 68 patients survived a median of 22 months from bone marrow transplant (range, 7 to 81 months). The actuarial probabilities of overall survival and leukemia-free survival at 2 years for the sibling donor group were 73% (95% CI, 60% to 86%) and 72% (CI, 60% to 84%), respectively, and for the volunteer donor group, 47% (CI, 31% to 63%) and 42% (CI, 26% to 58%) (P = 0.07 and 0.05, respectively). However, after adjustment for duration of disease, overall and disease-free survival in the two donor groups did not differ significantly. A major problem was an increased incidence of severe viral infection in the volunteer unrelated donor group (19 episodes in 16 of 46 patients compared with 7 episodes in 7 of 57 sibling donor patients, P = 0.01). The actuarial incidence of chronic graft-versus-host disease (GVHD) was higher in volunteer unrelated donor patients (77% [CI, 63% to 91%] compared with 49% [CI, 35% to 63%]; P = 0.02) but that of acute GVHD was not. The median performance status of the survivors in the volunteer donor group is similar to that in the sibling donor group. The incidence of hematologic relapse in both groups so far is low.

Conclusion: Results appear to justify the continued use of volunteer donors in chronic-phase chronic myeloid leukemia, but infection and chronic GVHD are still major problems.


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Figure 1.
Overall (top) and leukemia-free (bottom) survival.

Surviving patients are represented by vertical tick marks. Survival analysis was performed on 31 August 1992. SD = sibling donor; VUD = volunteer unrelated donor.

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Figure 2.
Overall (top) and leukemia-free survival in bone marrow transplant recipients according to donor group adjusted for duration of disease.

SD = sibling donor; VUD = volunteer unrelated donor.

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Figure 3.
Cumulative number of viral infections versus time.

Nineteen severe viral infections occurred in 16 volunteer unrelated donor patients and 7 in 7 sibling donor patients. BMT = bone marrow transplant; SD = sibling donor; VUD = volunteer unrelated donor.

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