Graft Source and HLA-Matching Degree-Based Analyses of Long-Term Outcomes of Unrelated Donor Transplants in Adult High-Risk Acute Lymphoblastic Leukemia: Similar Outcomes Between Bone Marrow and Peripheral Blood Progenitor Cells Transplants,

Adults with high-risk acute lymphoblastic leukemia (ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated donor stem cell transplantation (URD-SCT) if a matched sibling donor is not available. However, long-term results of URD-SCT, especially based on HLA-matching degree and graft source, are scarce in adult high-risk ALL. To assess the effect of HLA-matching degree and graft source, we analyzed long-term outcomes of 109 consecutive URD transplants with adult high-risk ALL (2000–2008).

Using allele-level typing, graft sources were classified as 8/8-matched bone marrow (BM; n=31), 8/8-matched peripheral blood progenitor cells (PBPC; n=19), 7/8-matched BM (n=35), and 7/8-matched PBPC (n=24). Patients received total body irradiation (≥12 Gy)-based full-intensity (n=95) or reduced-intensity (fludarabine plus melphalan; n=14) conditioning regimens. All patients received the same graft-versus-host disease prophylaxis consisting of tacrolimus plus methotrexate. Antithymocyte globulin was administered to all 7/8-matched transplants.

After a median follow-up of 57 months, the 5-year cumulative incidence of relapse was 19% for 8/8-matched BM, 16% for 8/8-matched PBPC, 37% for 7/8-matched BM, and 48% for 7/8-matched PBPC (P=0.013). Conversely, no significant difference in the 5-year cumulative incidence of non-relapse mortality was observed between each group of patients. Consequently, disease-free survival (DFS) at 5 years was inferior using 7/8-matched BM (46%) or 7/8-matched PBPC (42%), compared with 8/8-matched grafts (65% for BM and 58% for PBPC) (P=0.044). However, when considering pre-transplant disease status and conditioning intensity, no influence of HLA-matching degree and graft source on outcomes was found in transplants receiving full-intensity conditioning in first complete remission (CR1). Notably, outcomes were similar between BM and PBPC transplants in each group of patients showing the same HLA-matching degree. Regardless of HLA-matching degree and graft source, pre-transplant disease status (CR1 versus >CR1) was an independent predictive factor affecting relapse (RR 3.09, P=0.005) and DFS (RR 2.69, P=0.003). The absence of chronic graft-versus-host disease was also associated with higher relapse (RR 5.60, P<0.001) and poorer DFS (RR 2.49, P=0.005).

Our long-term data suggest that outcomes are similar for transplantation using BM or PBPC in the setting of 8/8-matched or 7/8-matched URD-SCT in adult high-risk ALL.

No relevant conflicts of interest to declare.