Minimal residual disease in acute lymphoblastic leukemia: optimal methods and clinical relevance, pitfalls and recent approaches.

After advances in experimental and clinical testing, minimal residual disease (MRD) assay results are considered a determining factor in treatment of acute lymphoblastic leukemia patients. According to MRD assay results, bone marrow (BM) leukemic burden and the rate of its decline after treatment can be directly evaluated. Detailed knowledge of the leukemic burden in BM can minimize toxicity and treatment complications in patients by tailoring the therapeutic dose based on patients' conditions. In addition, reduction of MRD before allo-HSCT is an important prerequisite for reception of transplant by the patient. In direct examination of MRD by morphological methods (even by a professional hematologist), leukemic cells can be under- or over-estimated due to similarity with hematopoietic precursor cells. As a result, considering the importance of MRD, it is necessary to use other methods including flow cytometry, polymerase chain reaction (PCR) amplification and RQ-PCR to detect MRD. Each of these methods has its own advantages and disadvantages in terms of accuracy and sensitivity. In this review article, different MRD assay methods and their sensitivity, correlation of MRD assay results with clinical symptoms of the patient as well as pitfalls in results of these methods are evaluated. In the final section, recent advances in MRD have been addressed.