Late relapse of childhood acute lymphoblastic leukemia and pcr-monitoring of minimal residual disease: how much time can elapse between "molecular" and clinical relapse?

Leukemia relapse, the most frequent cause of treatment failure in childhood acute lymphoblastic leukemia (ALL), usually occurs in the bone marrow within three years after achieving complete remission (CR). Together with flow-cytometry and analysis of breakpoint fusion regions of chromosome aberrations, detection of clone-specific immunoglobulin and T-cell receptor gene rearrangements by PCR offers the opportunity to identify leukemic cells undetectable at light microscopy,1 allowing detection of leukemic cells during CR even at very low concentration (<=10-4). Repeated measurement of PCR-defined minimal residual disease (MRD) is currently considered one of the most promising strategies for treatment tailoring and understanding ALL biology.2-4 The growth pattern of relapsing ALL clones remains unclear. In particular no information is available on the results of PCR-defined MRD in children who suffer a late relapse.