USE OF PARTIALLY MISMATCHED RELATED DONORS EXTENDS ACCESS TO ALLOGENEIC MARROW TRANSPLANT

Most patients requiring allogeneic bone marrow transplant (allo-BMT) d o not have an HLA-matched sibling donor. A phenotypically matched unre lated donor graft has been made available for approximately 50% of Cau casians and less than 10% of ethnic and racial minorities in need. How ever, almost all patients have a readily available partially mismatche d related donor (PMRD). We summarize our experience with 72 patients w ho ranged from 1 to 50 years of age (median, 16 years) and who were re cipients of a PMRD allo-BMT from haploidentical family members followi ng conditioning therapy using total body irradiation (TBI) and multiag ent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppr ession were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patient s who failed to engraft achieved engraftment after Secondary transplan t. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patie nts; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patient s. 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 anal ysis were (1) a lower TBI dose and 3-antigen rejection mismatch decrea sed stable engraftment (P = .005 and P = .002, respectively); (2) a hi gher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dos e increased chronic GVHD (P = 0.16); and (4) a high-risk disease categ ory increased treatment failure from relapse or death (P = .037). A PM RD 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 associ ated with long-term successful outcome after PMRD allo-BMT. When allog eneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclus ion of all ethnic or racial groups. (C) 1997 by The American Society o f Hematology.