Detection and quantification of residual disease in chronic myelogenous leukemia

The degree of tumor load reduction after therapy is an important prognostic factor for patients with CML. Conventional metaphase analysis has been con sidered to be the 'gold standard' for evaluating patient response to treatm ent but this technique normally requires bone marrow aspiration and is ther efore invasive. The frequency of cytogenetic analyses can be considerably r educed if patients are also monitored by molecular methods, which can be pe rformed on peripheral blood specimens. Of the various techniques available, most attention has been paid to RT-PCR for BCR-ABL mRNA since this is by f ar the most sensitive. Simple, non-quantitative RT-PCR analysis gives only limited information on patients after treatment. Quantitative RT-PCR assays have been developed to monitor the kinetics of residual BCR-ABL transcript s over time. Variables in the quantitative PCR assay may be controlled for by quantification of transcripts of a normal gene (eg ABL or glucose-6-phos phate dehydrogenase, G6PD) as an internal standard. After allogeneic stem c ell transplantation, most patients become RT-PCR negative, often after a pe riod of low level positivity that may persist for several months. Those pat ients destined to relapse are characterized by the reappearance and/or risi ng levels of BCR-ABL transcripts. In contrast, for patients treated with in terferon-alpha (IFN) residual disease is rarely, if ever, eliminated. The a ctual level of minimal residual disease in complete cytogenetic responders to IFN correlates with the probability of relapse. New quantitative real ti me procedures promise to simplify the protocols that are currently in use, but standardization and the introduction of rigorous, internationally accep ted controls are required to enable RT-PCR to become a robust and routine b asis for therapeutic decisions.