title: Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate.
abstract: Survival among chronic myelogenous leukemia (CML) patients can be linked to the reduction in leukemic cell burden. Treatment with imatinib mesylate results in a high frequency of complete cytogenetic response, which can be further stratified using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We have serially monitored peripheral blood and bone marrow BCR-ABL transcripts using qRT-PCR in CML patients commencing imatinib therapy, and compared the results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with Philadelphia chromosome positive CML in first chronic phase were treated with imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33 mo). Every third month the product of the BCR-ABL fusion gene was evaluated in both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL transcript values agreed well with cytogenetic data. Blood and bone marrow specimens gave comparable values for BCR-ABL transcripts. Before start of imatinib therapy there was a considerable variation in BCR-ABL transcripts among the patients, ranging approximately one log (base 10). Similarly, patients with a complete cytogenetic response following imatinib therapy had variable BCR-ABL transcript levels, ranging at least three logs (base 10). The major decline in BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The decline in BCR-ABL transcripts, following imatinib therapy, appears to level off at 12-15 mo. Two late responders were identified with a still decreasing level in BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA quantification in peripheral blood is suitable for routine monitoring of the response to treatment and long-term disease status in CML, especially in patients who have achieved a complete cytogenetic response. A plateau in BCR-ABL transcripts seems to have been reached after 12-15 mo of imatinib treatment; however, some "late responders" are seen.
authors.affiliation: Department of Internal Medicine, Haematology section, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. mats.hardling@medic.gu.se
authors.forename: Mats
authors.initials: M
authors.lastname: Hardling
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Birgitta
authors.initials: B
authors.lastname: Swolin
authors.forename: Dick
authors.initials: D
authors.lastname: Stockelberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Gustavsson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ekeland-Sjöberg
authors.forename: Hans
authors.initials: H
authors.lastname: Wadenvik
authors.forename: Anne
authors.initials: A
authors.lastname: Ricksten
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis*; D001853:Bone Marrow; D005260:Female; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D016315:Proto-Oncogene Proteins c-abl / Q000032:analysis*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl