Minimal residual disease in acute leukemias in children and adults

Abstract

Biological and genetic heterogeneity of acute leukemias is a major cause of therapeutic difficulties. Response to chemotherapy is one of the most important prognostic factors in this group of diseases. In acute lymphoblastic leukemia (ALL), and progressively more in acute myeloid leukemia (AML), the best parameter of that response is the presence of minimal residual disease (MRD). MRD monitoring is performed based on the flow cytometer analysis of leukemic immunophenotypes or detection of gene rearrangement by PCR. Both methods are characterized by high sensitivity and specificity, which clearly distinguishes them from the standard morphologic examination. This review presents the current state of knowledge of the importance and use of MRD in children and adults, in ALL and AML, emphasizing similarities and differences. Current opinions show that the MRD is the most important prognostic factor in ALL and an important factor in AML. Based on current data in children and adults, it seems that in acute lymphoblastic leukemia, presence of MRD is a continuous variable; the older the patient, the higher the risk of MRD and therapy failure. This paper presents also a new insight to the concept of MRD, because of the presence of leukemic stem cells that survive chemotherapy in AML and any of the maturational stages of leukemia-propagating cells in ALL. This idea combines the phenomenon of drug resistance of tumor stem cells and the presence of residual cells undetectable by methods of optical microscopy after applied chemotherapy. The concept of leukemic stem cells explains the occurrence of resistant clones both in ALL and AML. Based on studies of genetic profiles, there is growing evidence to suggest that acute leukemia is a highly heterogeneous disease, which goes hand in hand with the hierarchy of leukemic stem cells and leukemia initiating cells. In the light of the current knowledge based on MRD, it seems necessary to review the concept of complete remission in MRD-positive leukemic patients.