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Use of partially mismatched related donors extends access to allogeneic
marrow transplant
PJ Henslee-Downey, SH Abhyankar, RS Parrish, AR Pati, KT Godder, WJ Neglia, KS Goon-Johnson, SS Geier, CG Lee and AP Gee
Division of Transplantation Medicine of the University of South Carolina
School of Medicine, Richland Memorial Hospital, Columbia, USA.
Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not
have an HLA-matched sibling donor. A phenotypically matched unrelated donor
graft has been made available for approximately 50% of Caucasians and less
than 10% of ethnic and racial minorities in need. However, almost all
patients have a readily available partially mismatched related donor
(PMRD). We summarize our experience with 72 patients who ranged from 1 to
50 years of age (median, 16 years) and who were recipients of a PMRD
allo-BMT from haploidentical family members following conditioning therapy
using total body irradiation (TBI) and multiagent, high-dose chemotherapy.
T-cell depletion and post- BMT immunosuppression were combined for
graft-versus-host disease (GVHD) prophylaxis. The probability of
engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft
achieved engraftment after secondary transplant. Grade II to IV acute GVHD
was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was
seen in 4 of 48 (8%) evaluable patients. There was a statistically
significant difference in 2-year survival probability between low-risk and
high- risk patients (0.55 v 0.27, P = .048). Prognostic factors that
affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-
antigen rejection mismatch decreased stable engraftment (P = .005 and P =
.002, respectively); (2) a higher T-cell dose increased acute GVHD (P =
.058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a
high-risk disease category increased treatment failure from relapse or
death (P = .037). A PMRD transplant can be performed with acceptable rates
of graft failure and GVHD. Using sequential immunomodulation, the disease
status at the time of transplant is the only prognostic factor
significantly associated with long-term successful outcome after PMRD
allo-BMT. When allogeneic rather than autologous BMT is indicated,
progression in disease status before transplant can be avoided using a PMRD
with equal inclusion of all ethnic or racial groups.
Volume 89,
Issue 10,
pp. 3864-3872,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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