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

Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic leukemia (ALL) received a matched unrelated donor transplant using marrow procured 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 patients in CR1, 17% in CR2/3, and 5% in PIF or relapse. Treatment-related mortality (TRM) and relapse mortality, estimated as competing risk factors, were 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 with a median follow-up of 24 months (range, 3-97). Multivariable analysis showed that CR1, shorter interval from diagnosis to transplantation, DRB1 match, negative cytomegalovirus (CMV) serology (patient and donor), and presence of the Philadelphia chromosome, t(9;22), were independently associated with better disease-free survival (DFS). Transplantation in CR and presence of t(9;22) were associated with lower risk of relapse. Shorter interval from diagnosis to transplantation, DRB1-match, negative CMV, higher marrow cell 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 to results obtained with chemotherapy alone and matching results following HLA-identical sibling transplantation.