Poster Session I: Acute lymphoblastic leukemia - Clinical
B-cell acute lymphoblastic leukemia (B-ALL) is a clinically and biologically heterogeneous disease that is characterized by the clonal expansion of developmentally arrested B-cell precursors. Despite significant improvements in the management of this disease in children, the prognosis of adult patients remains poor. Identifying new prognostic markers is necessary to help select the best therapeutic schedules. Wilms' tumor gene 1 (WT1) is a transcription factor that is overexpressed in diverse neoplasms, including acute leukemia. The prognostic role of WT1 in ALL is still controversial. No study has focused on the prognostic role of WT1 expression in adult B-ALL patients receiving chemotherapy only.
To investigate the prognostic value of WT1 expression in adult patients with B-ALL.
The WT1 transcript levels of 162 de-novo adult B-ALL patients were determined by TaqMan-based real time quantitative PCR (RQ-PCR) at the time of diagnosis. Eighty-eight patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Survival functions were estimated by the Kaplan-Meier method and compared by the log-rank test. Cumulative incidences were estimated for relapse to accommodate competing risks. A Cox proportional hazard regression model was used to determine the associations between WT1 transcript levels and CIR, RFS and OS.
WT1 overexpression was defined as a transcript level higher than 0.50%, which is the upper limit in normal bone marrow. WT1 overexpression was identified in 66.0% of the patients. WT1 overexpression was an independent positive prognostic factor for the cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) in patients who received chemotherapy only (CIR: HR = 0.236 [95% confidence interval 0.094-0.592]; P = 0.002; RFS: HR = 0.223 [0.092-0.543]; P = 0.001; OS: HR = 0.409 [0.214-0.783]; P = 0.007) and in patients who did not have BCR-ABL fusion or KMT2A rearrangements (CIR: HR = 0.431 [0.201-0.921]; P = 0.030; RFS: HR = 0.449 [0.224-0.899]; P = 0.024; OS: HR = 0.521 [0.278-0.977]; P = 0.042). However, WT1 overexpression had no prognostic value in patients who received allogenic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, allo-HSCT could improve the prognosis of patients with low WT1 expression.
Therefore, testing for WT1 expression at the time of diagnosis may predict outcomes in adult B-ALL patients who receive only chemotherapy and who do not have the BCR-ABL fusion gene or KMT2A rearrangements. Allo-HSCT may improve the prognosis of patients with low WT1 transcript levels.