Detection of T315I using digital polymerase chain reaction in allogeneic transplant recipients with Ph-positive acute lymphoblastic anemia in the dasatinib era

Abstract

Dasatinib, a potent tyrosine kinase inhibitor (TKI), is currently used as first-line treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, emergence of the T315I mutation has been found to be a main cause of failure after dasatinib-containing treatments. We assessed the prognostic value of small clones with the T315I mutation at specific time points using the novel technology digital polymerase chain reaction (PCR), which is more sensitive than direct sequencing. This study included 25 consecutive adult patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) following dasatinib-based chemotherapy at our center. Among six patients who experienced hematologic relapse after HSCT, four harbored the T315I mutation at relapse. However, the detection of small subclones with T315I at either diagnosis or HSCT was not associated with an increased risk of relapse. In contrast, all patients with the T315I mutation at molecular relapse after HSCT (n = 4) eventually had a hematologic relapse, and only two of the 10 patients without the T315I mutation at molecular relapse after HSCT relapsed. In conclusion, the detection of small clones with the T315I mutation at molecular relapse after HSCT, but not before HSCT, could support an early clinical decision to change treatments.