SOHO State of the Art Updates and Next Questions, Measurable Residual Disease in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Assessment of measurable residual disease (MRD) provides important prognostic information and can inform decision-making about appropriate consolidative therapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Many contemporary treatment protocols for Ph+ ALL achieve high rates of MRD negativity, and several analyses suggest that allogeneic hematopoietic stem cell transplant in first remission can be safely deferred in most patients who achieve MRD negativity by PCR for BCR::ABL1 within 3 months. Given the close association between achievement of MRD negativity and favorable long-term outcomes in Ph+ ALL, MRD response rates may aid in the evaluation of novel regimens, particularly in the absence of randomized data or robust survival data. While most studies in Ph+ ALL have used PCR for BCR::ABL1 to measure MRD and correlate with outcomes, this assay has several limitations. PCR or next-generation sequencing-based assays for immunoglobin or T-cell receptor (IG/TR) gene rearrangements may provide a more accurate assessment of clinically significant MRD in Ph+ ALL, particularly in patients with multilineage involvement of BCR::ABL1. Herein, we discuss the prognostic and therapeutic role of MRD in Ph+ ALL. We review the available methods of MRD assessment in Ph+ ALL and discuss the advantages of MRD assays that track IG/TR rearrangements rather than BCR::ABL1.