Clinical implications of qualitative and quantitative polymerase chain reaction analysis in the monitoring of patients with chronic myelogenous leukemia. The European Investigators on Chronic Myeloid Leukemia Group.
Recent progress in the development of diagnostic techniques has greatly facilitated the monitoring of minimal residual disease (MRD) in patients with hematologic neoplasia. The presence of genetic markers, such as the BCR/ABL rearrangement in chronic myelogenous leukemia (CML), has allowed highly sensitive detection of residual leukemic cells by polymerase chain reaction (PCR). However, complete eradication of the leukemic clone may not be a necessary prerequisite for long-term remission or cure. This observation limits the value of qualitative PCR analysis for prediction of progressive disease and highlights the need to monitor the proliferative activity of the malignant clone in order to permit timely detection of impending relapse. We have developed a quantitative PCR protocol based on the principle of competitive enzymatic amplification and demonstrated its applicability to the monitoring of treatment efficacy and early assessment of clonal expansion in patients with CML. We have introduced the term 'PCR relapse' for the detection of a proliferating leukemic clone by serial quantitative PCR (Q-PCR) analyses. At a recent meeting of the group of European Investigators on Chronic Myelogenous Leukemia (EICML Group) the use of Q-PCR investigation has been recommended for the monitoring of MRD, and the detection of PCR relapse was accepted as a basis for therapeutic decisions. This article discusses problems in the interpretation of MRD by PCR and presents guidelines for the clinical use of qualitative and quantitative PCR analyses.
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Children's Cancer Research Institute, St. Anna Children's Hospital, Vienna, Austria.
D016026:Bone Marrow Transplantation; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000628:therapy; D016133:Polymerase Chain Reaction
D007372:Interferons