Presence of measurable residual disease (MRD) may be prognostic of survival and relapse following treatment for acute lymphoblastic leukemia (ALL), but there are numerous methods to assess and interpret MRD. A recent review in the American Journal of Hematology emphasized the importance of evaluating MRD and provided recommendations for assessment and treatment approaches.
The primary MRD assessment methods recommended in the report included multiparameter flow cytometry (MFC), quantitative polymerase chain reaction (qPCR)-based techniques, and next-generation sequencing (NGS). Sensitivity varies for each: In regular practice, MFC provides sensitivity on the order of 10-4, qPCR on the order of 10-4 to 10-5, and NGS on the order of 10-6. The authors considered a sensitivity of at least 10-4 necessary for appropriate MRD assessment. NGS was highlighted for its ability to potentially track clonal evolution, but it is analytically more complex than the other methods. Regardless of assessment method, the authors advised use of bone marrow rather than peripheral blood samples.
The authors made recommendations on the timing of MRD assessment based on phase of frontline or salvage therapy. They also suggested detailed treatment approaches for newly diagnosed patients based on results of MRD assessments and with respect to cytogenetic and genomic risk factors and disease type. In some circumstances of MRD positivity or high-risk disease, allogeneic hematopoietic stem cell transplant (HSCT) was highlighted as an option, sometimes including pretreatment with blinatumomab.
The authors concluded that “NGS holds significant promise” for accurate MRD assessment, though it should be tested more with peripheral blood samples. They also suggested further research to refine the prognostic value of MRD in regard to genetic changes in ALL and to determine whether novel treatments aided by MRD assessment can circumvent reliance on HSCT.
1. Short NJ, Jabbour E, Albitar M, et al. Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of North American experts [published online November 5, 2018]. Am J Hematol. doi: 10.1002/ajh.25338