In patients with acute leukemia, peripheral blood and bone marrow samples are periodically examined to monitor response to therapy and recovery of normal hematopoiesis. This is traditionally done by assessing cell morphology, a practice that lacks sensitivity and is prone to errors. Assays that can detect minimal residual disease (MRD), referring to leukemic cells undetectable by standard methods, have a higher sensitivity than morphology and are generally much more precise.
The most reliable methods to study MRD in acute leukemia are flow cytometric detection of aberrant immunophenotypes and polymerase chain reaction amplification of rearranged immunoglobulin and T-cell receptor genes. The latter approach has been refined by deep-sequencing analysis. These methods can detect 1 leukemic cell among 10,000 or greater normal bone marrow or peripheral blood cells and are applicable to most patients with acute lymphoblastic leukemia (ALL). In patients with acute myeloid leukemia (AML), flow cytometry is the only method that allows MRD monitoring in the majority of patients. This approach has been considerably improved by the recent discovery of new markers that can be used to distinguish AML cells from normal myeloid cells, and by the availability of increasingly sophisticated analytical software.
It is indisputable that MRD monitoring in patients with newly diagnosed ALL and AML provides critical information to guide treatment decisions. MRD methods can refine assessment of early treatment response, and provide powerful prognostic parameters for risk-classification algorithms. More recent applications include the use of MRD using an eligibility or response criterion for new agents. In the context of chimeric antigen receptor (CAR)-T cell therapy, MRD by flow cytometry allows a precise assessment of the immunophenotype of residual leukemic cells, defining the proportion of cells expressing the targeted antigen before and after CAR-T cell infusion.
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