Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis.

Abstract

BackgroundTargeted therapy has revolutionized the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact.MethodsSeventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed.ResultsSeventeen patients had blasts with the pattern of LPCs (CD34+CD38−CD58−), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+CD38−CD58− phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38−CD58− phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38− CD58− phenotype was an independent risk factor for overall survival.ConclusionThe presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.