Effect of Stem Cell Source on Transplant Outcomes in Adults with Acute Leukemia: A Comparison of Unrelated Bone Marrow (BM), Peripheral Blood (PB) and Cord Blood (CB)

Abstract

Currently, in the absence of an HLA matched sibling donor, an unrelated adult donor matched at 8 of 8 alleles for HLA A, B, C, DRB1 is preferred. However, the conditional probability of finding an 8 of 8 matched adult donor based on a preliminary analysis of the current National Marrow Donor Program donor registry is 51% for Caucasians, 30% for Hispanics, 20% for Asians and 17% for African Americans. Over the past decade, CB has emerged as an alternative. Just as an 8/8 HLA match with allele level typing is standard for recipients of BM and PB, a cell dose ≥2.5 × 107 nucleated cells/kg and ≥4/6 match with antigen level typing for A and B and allele-level for DRB1 are standard for recipients of CB today. To determine the relative efficacy of the three stem cell sources in the current era, we evaluated outcomes in 1240 adults aged >16 years with acute leukemia (707 AML; 533 ALL) transplanted after a myeloablative transplant preparatory regimen in 2002–2006. The graft was T replete BM (243 8/8 and 111 7/8 matched), T replete PB (518 8/8 and 210 7/8 matched) or CB (38 5–6/6 and 110 4/6 matched). Median follow up was 2 years in all groups. Compared to recipients of BM and PB, recipients of CB were younger (median age: 29 vs. 39 and 35 years, respectively) and more likely to have ALL. Disease status at transplantation was similar in all groups. As shown previously in children, the incidence of neutrophil recovery (□500/ul at day−42) was poorest in recipients of CB (78%) as compared to PB (96%) and BM (92%). Importantly, incidence of transplantrelated mortality (TRM) was less in recipients of 8/8 matched PB and BM as compared to those transplanted with 7/8 PB or 7/8 BM (p=0.001) or CB (p<0.001; recognizing that 74% of CB transplants were mismatched at 2 antigens). Probabilities of leukemia-free (LFS) and overall survival (OS) rates were highest in recipients of 8/8 matched PB and BM with no significant differences in TRM, LFS and OS rates in recipients of CB and 7/8 matched PB and BM. Together, these data suggest that8/8 matched PB or BM donor should be the first choice for adults with acute leukemia if time permits andpartially matched CB with an adequate cell dose is a suitable alternative for the large proportion of patients for whom an 8/8 matched unrelated adult donor cannot be identified or transplant is urgent.On the basis of prior studies in children demonstrating the potential impact of cell dose on outcomes, new strategies continue to be explored to reduce TRM and increase the efficacy of CB for adults with acute leukemia.TRMRelapseLFSOSPB, matched at A, B, C, DRB1 (8 of 8)27%30%43%45%BM, matched at A, B, C, DRB1(8 of 8)26%28%46%48%CB, matched or mismatched (6/6 n=9, 5/6 n=29, 4/6 n= 110)41%26%33%35%PB, mismatched at 1-locus (7 of 8)42%24%33%36%BM, mismatched at 1-locus (7 of 8)37%26%34%38%