Sequential NGS for PhALL

We performed a comprehensive molecular analysis using next-generation sequencing (NGS) to identify genetic alterations during the disease course and the significance of allogeneic hematopoietic cell transplantation (HCT) in patients with Philadephia positive adult acute lymphoblastic leukemia (ALL). Among the 43 patients, 41 patients achieved complete remission (CR), and allogeneic HCT was performed in 25 patients (58%). Somatic mutations were detected in 10 patients, and the copy number aberration (CNA) was identified in 36 patients (84%) in diagnostic samples. The most frequent genetic abnormality was IKZF1 deletion (n=25, 58%). In all relapsed samples available for analysis (n=15), at least one genetic abnormality (loss, gain, or persistent) was observed compared to at the time of diagnosis. The most frequently mutated gene was ABL1 in 8 patients (53%). We could not find the prognostic significance of frequently detected genetic alterations at diagnosis. In multivariate analysis, receiving allogeneic HCT was a favorable prognostic factor for overall survival, relapse-free survival, and cumulative incidence of relapse (all, p<0.05). Our data support that the leukemic clone would progress with acquisition or loss of genetic alterations during leukemic relapse in most Ph-positive ALL. Allogeneic HCT prominently improves survival regardless of genetic alteration by NGS.