title: BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML.
abstract: Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P < .001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, OR 97201, USA. pressr@ohsu.edu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Press
authors.forename: Zac
authors.initials: Z
authors.lastname: Love
authors.forename: Ashlie A
authors.initials: AA
authors.lastname: Tronnes
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Thuan
authors.initials: T
authors.lastname: Tran
authors.forename: Solange
authors.initials: S
authors.lastname: Mongoue-Tchokote
authors.forename: Motomi
authors.initials: M
authors.lastname: Mori
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mauro
authors.forename: Michael W
authors.initials: MW
authors.lastname: Deininger
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D020732:Cytogenetic Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D013997:Time Factors
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl