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.

Abstract

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.