Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL.
Real-time quantitative polymerase chain reaction (PCR) for BCR-ABL mRNA in the peripheral blood (RQ-PCR) provides an accurate and reliable measure of response to therapy in chronic myeloid leukaemia (CML). We wanted to determine in what circumstances additional clinically relevant information was provided by simultaneous cytogenetic analysis in RQ-PCR monitored patients receiving imatinib treatment. We analysed 828 simultaneous RQ-PCR and bone marrow cytogenetic analyses from 183 patients with chronic phase CML with a median follow-up of 20 months. Cytogenetic progression was defined as Philadelphia (Ph)-positive clonal evolution, loss of complete cytogenetic response or an increase of > or = 20% Ph-positive cells. Cytogenetic progression occurred in 24/183 (13%) patients. At the time of cytogenetic progression, none of the 24 patients had a major molecular response (MMR; > or = 3-log reduction in BCR-ABL from standardised baseline). There were 320 RQ-PCR results from 95 patients indicating MMR. No abnormality was detected in any of the corresponding cytogenetic analyses. A policy of regular RQ-PCR monitoring with cytogenetic analysis targetted only to patients who have not achieved, or have lost MMR would represent a rational approach to monitoring and spare most patients the discomfort of multiple marrow aspirates. This approach depends upon availability of an accurate, reproducible RQ-PCR assay with ongoing quality assurance.
Division of Haematology, Institute of Medical & Veterinary Science, Adelaide, Australia. david.ross@imvs.sa.gov.au
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Ross
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Branford
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Moore
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Hughes
D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology*; D002869:Chromosome Aberrations; D003001:Cloning, Molecular; D020732:Cytogenetic Analysis / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl