Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factorsdetermining outcome

Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic leuk emia (ALL) received a matched unrelated donor transplant using marrow procu red by National Marrow Donor Program (NMDP) collection centers and sent out to 46 transplant centers worldwide. Poor risk was defined by the presence of the translocations t(9;22) (n = 97), or t(4;11) (n = 25), or t(1;19) (n = 5). Sixty-four patients underwent transplantation in first remission (CR1 ), 16 in CR2 or CR3, and 47 patients had relapsed ALL or primary induction failure (PIF). Overall survival at 2 years from transplant was 40% for pati ents in CR1, 17% in CR2/3, and 5% in PIF or relapse. Treatment-related mort ality (TRM) and relapse mortality, estimated as competing risk factors, wer e 54% and 6%, respectively, in CR1, 75% and 8% in CR2/3, and 64% and 31% in PIF or relapse. Currently 23 CR1 patients are alive and free of disease wi th a median follow-up of 24 months (range, 3-97). Multivariable analysis sh owed that CR1, shorter interval from diagnosis to transplantation, DRB1 mat ch, negative cytomegalovirus (CMV) serology (patient and donor), and presen ce of the Philadelphia chromosome, t(9;22), were independently associated w ith better disease-free survival (DFS). Transplantation in CR and presence of t(9;22) were associated with lower risk of relapse. Shorter interval fro m diagnosis to transplantation, DRB1-match, negative CMV, higher marrow cel l dose, and Karnofsky score of 90 or higher were associated with less TRM, These results indicate that, despite a relatively high TRM, the low relapse rate resulted in a 37% +/- 13% DFS for CR1 patients, comparing favorably t o results obtained with chemotherapy alone and matching results following H LA-identical sibling transplantation. (Blood, 2001;97:1572-1577) (C) 2001 b y The American Society of Hematology.