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Blood, 1 February 2002, Vol. 99, No. 3, pp. 806-814
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Superior survival associated with transplantation of matched
unrelated versus one-antigen-mismatched unrelated or highly human
leukocyte antigen- disparate haploidentical family donor marrow
grafts for the treatment of hematologic malignancies: establishing
a treatment algorithm for recipients of alternative donor
grafts
William R. Drobyski,
John Klein,
Neal Flomenberg,
Daniel Pietryga,
David H. Vesole,
David A. Margolis, and
Carolyn A. Keever-Taylor
From the Bone Marrow Transplant Program, the Division
of Biostatistics, and the Departments of Medicine and Pediatrics,
Medical College of Wisconsin, Milwaukee.
The purpose of this study was to compare transplantation outcomes
in patients with hematologic malignancies who received marrow grafts
from either phenotypically matched unrelated, one- antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning
regimen and a graft-versus-host disease (GVHD) prophylaxis schedule
with the exception of recipients of haploidentical marrow grafts, who
received antithymocyte globulin after bone marrow transplantation as
additional immunosuppression. There was no statistically significant
difference in the rate of engraftment, or the cumulative incidences of
acute and chronic GVHD between any of the 3 groups. The 2-year
cumulative incidence of relapse was lower in matched unrelated patients
(25%, P = .01) and mismatched unrelated patients (26%,
P = .014) than in haploidentical patients (42%).
Transplant-related mortality was significantly higher in recipients of
mismatched unrelated grafts (45%, P = .01) and
haploidentical grafts (42%, P = .001) compared with
recipients of matched unrelated marrow grafts (23%). This resulted in
a significantly higher probability of overall survival for matched
unrelated patients (58%) versus either mismatched unrelated (34%,
P = .01) or haploidentical (21%, P = .002)
patients. There was no statistically significant difference in survival
between patients who received mismatched unrelated grafts versus
those who received haploidentical grafts. This study supports a donor
selection algorithm whereby patients who lack a closely matched family
donor be offered a phenotypically matched unrelated donor if available.
There is no apparent advantage to using a mismatched unrelated versus a
highly HLA-disparate family donor.
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