Association between measurable residual disease kinetics and outcomes of Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract

The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has improved dramatically. Although measurable residual disease (MRD) kinetics during pretransplant treatment has been recently reported to correlate with patient outcomes, it is unclear whether prognosis is better if the MRD falls below the detection sensitivity soon after induction therapy. We retrospectively analyzed data of 37 Ph + ALL patients who were treated with autologous or allogeneic stem cell transplantation (auto-SCT, allo-SCT) at our institute from 2003 to 2019. Based on MRD kinetics, patients were divided into three groups: early responders (MRD became negative after induction therapy [n = 10, 27.0%]); late responders (MRD remained positive after induction therapy and became negative just before SCT [n = 12, 32.4%]); and poor responders (MRD was positive until just before SCT [n = 15, 40.5%]). The 5-year disease-free survival (DFS) rates for the three groups were 80.0%, 60.0%, and 29.9%, respectively (P = 0.037). The 5-year overall survival rates were not significantly different. The 5-year relapse rates were 0.0%, 31.7%, and 49.5%, respectively (P = 0.045). Non-relapse mortality (NRM) rates were similar among the three groups. Subgroup analysis for the cases that received posttransplantation tyrosine kinase inhibitor maintenance therapy revealed that DFS was similarly dependent on MRD kinetics (P = 0.022). This study clarified that MRD kinetics was a significant prognosticator for DFS and relapse rate in Ph + ALL.

Keywords: Dasatinib; Hematopoietic stem cell transplantation; Imatinib; Measurable residual disease; Philadelphia chromosome-positive acute lymphoblastic leukemia; Tyrosine kinase inhibitor.