Quantitative reverse transcription polymerase chain reaction should not replace conventional cytogenetics for monitoring patients with chronic myeloid leukemia during early phase of imatinib therapy

• Published in: Haematologica (Roma) 2004-01, Vol.89 (1), p.49-57
• Main Authors: Lange, T, Bumm, T, Otto, S, Al-Ali, HK, Kovacs, I, Krug, D, Kohler, T, Krahl, R, Niederwieser, D, Deininger, MW
• Format: Article
• Language: English
• Subjects: Adult; Aged; Benzamides; Biological and medical sciences; Bone Marrow - chemistry; Bone Marrow - metabolism; Bone Marrow - pathology; Chromosome aberrations; Cytogenetic Analysis - methods; Cytogenetic Analysis - statistics & numerical data; Disease-Free Survival; Female; Fusion Proteins, bcr-abl - blood; Fusion Proteins, bcr-abl - genetics; Glyceraldehyde-3-Phosphate Dehydrogenases - blood; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; In Situ Hybridization, Fluorescence - methods; In Situ Hybridization, Fluorescence - statistics & numerical data; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical genetics; Medical sciences; Middle Aged; Multivariate Analysis; Philadelphia Chromosome; Piperazines - therapeutic use; Prognosis; Pyrimidines - therapeutic use; Remission Induction - methods; Reverse Transcriptase Polymerase Chain Reaction - methods; Reverse Transcriptase Polymerase Chain Reaction - statistics & numerical data
• ISSN: 0390-6078; 1592-8721

Department of Hematology, University of Leipzig, Germany. BACKGROUND AND OBJECTIVES: Imatinib is the new standard drug treatment for patients with chronic myelogenous leukemia (CML). Quantitative reverse transcription-polymerase chain reaction (qPCR) for detection of BCR-ABL transcripts is frequently used for monitoring patients in addition to or instead of conventional cytogenetics, although its place in the overall diagnostic framework is not yet clear. In this study, we compared qPCR and conventional cytogenetics for monitoring of patients during the early phases of imatinib therapy. DESIGN AND METHODS: One hundred and seventeen patients treated with imatinib for CML in chronic or accelerated phase were prospectively followed with qPCR and karyotyping. Comparisons were made between both methods and between qPCR results from bone marrow and peripheral blood. To determine the prognostic impact of qPCR and cytogenetics during the early phase of imatinib treatment on subsequent cytogenetic response and progression-free survival (PFS), a multivariate model was generated that included established prognostic baseline variables. RESULTS: We found a significant correlation between the proportion of Philadelphia (Ph) chromosome-positive metaphases and qPCR in the bone marrow and peripheral blood. Low qPCR values after 3 months of therapy were correlated with major cytogenetic response (MCyR) at 6 months and PFS at 2 years. However, in multivariate analysis, the cytogenetic response at 3 months emerged as the only independent parameter predictive of MCyR at 6 months and PFS at 2 years. INTERPRETATION AND CONCLUSIONS: Our data suggest that conventional karyotyping should remain the standard method for following patients on imatinib during the early phases of therapy.