Clinical significance of minimal residual disease in leukemia detected by polymerase chain reaction: is molecular remission a milestone for achieving a cure?

Polymerase chain reaction (PCR) technology has been useful in clarifying molecular or minimal residual disease (MRD) status in patients with leukemia. Although PCR has several inherent problems, accumulated data have demonstrated that patients with leukemia harbor PCR-detectable residual disease for a certain period despite clinical remission. This has been for approximately 1 year in childhood acute lymphoblastic leukemia and adult acute promyelocytic leukemia after chemotherapy and for approximately 2 years in chronic myelogenous leukemia after bone marrow transplantation. Ultimately, PCR-undectable residual disease is necessary for achieving cures in most patients. However, it is difficult to make an early prediction of subsequent relapse after obtaining PCR negatively, since the emergence of PCR-detectable disease occurs only several months before clinical relapse. Therefore, PCR negativity is necessary but not sufficient for achieving cures in most patients with leukemia. Periods of persistent PCR-detectable disease will require further investigations for relapse prediction. More accurate serial quantitation would clarify a precise MRD status in leukemia patients and might allow for more accurate prediction of relapse. Since PCR-undectable residual disease is necessary for cures in most patients, it can be proposed that a "molecular remission", defined as PCR-undetectable disease, is a milestone and target for achieving cure by cytoreductive therapy.