Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Relapse of Ph chromosome-positive ALL (Ph + ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph + ALL, a xenograft assay recently determined that LPCs are enriched in the CD34 + CD38 − CD58 − fraction. Therefore, the prognostic significance of LPCs in Ph + ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph + ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58–FITC/CD10–PE/ CD19–APC–Cy7/CD34–PerCP/CD45–Vioblue/ CD38–APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34 + CD38 − CD58 − group ( N =15) and other phenotype group ( N =65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34 + CD38 − CD58 − group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34 + CD38 − CD58 − LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34 + CD38 − CD58 − LPCs at diagnosis, and BCR–ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34 + CD38 − CD58 − LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.