title: Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR.
abstract: Around 40-50% of patients with chronic myeloid leukemia (CML) who achieve a stable complete molecular response (CMR; undetectable breakpoint cluster region-Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA) on imatinib can stop therapy and remain in CMR, at least for several years. This raises the possibility that imatinib therapy may not need to be continued indefinitely in some CML patients. Two possible explanations for this observation are (1) CML has been eradicated or (2) residual leukemic cells fail to proliferate despite the absence of ongoing kinase inhibition. We used a highly sensitive patient-specific nested quantitative PCR to look for evidence of genomic BCR-ABL1 DNA in patients who sustained CMR after stopping imatinib therapy. Seven of eight patients who sustained CMR off therapy had BCR-ABL1 DNA detected at least once after stopping imatinib, but none has relapsed (follow-up 12-41 months). BCR-ABL1 DNA levels increased in all of the 10 patients who lost CMR soon after imatinib cessation, whereas serial testing of patients in sustained CMR showed a stable level of BCR-ABL1 DNA. This more sensitive assay for BCR-ABL1 provides evidence that even patients who maintain a CMR after stopping imatinib may harbor residual leukemia. A search for intrinsic or extrinsic (for example, immunological) causes for this drug-free leukemic suppression is now indicated.
authors.affiliation: Department of Haematology, Flinders Medical Centre, SA Pathology, Bedford Park, Adelaide, South Australia, Australia. david.ross@health.sa.gov.au
authors.forename: D M
authors.initials: DM
authors.lastname: Ross
authors.forename: S
authors.initials: S
authors.lastname: Branford
authors.forename: J F
authors.initials: JF
authors.lastname: Seymour
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: C
authors.initials: C
authors.lastname: Arthur
authors.forename: P A
authors.initials: PA
authors.lastname: Bartley
authors.forename: C
authors.initials: C
authors.lastname: Slader
authors.forename: C
authors.initials: C
authors.lastname: Field
authors.forename: P
authors.initials: P
authors.lastname: Dang
authors.forename: R J
authors.initials: RJ
authors.lastname: Filshie
authors.forename: A K
authors.initials: AK
authors.lastname: Mills
authors.forename: A P
authors.initials: AP
authors.lastname: Grigg
authors.forename: J V
authors.initials: JV
authors.lastname: Melo
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006086:Graft vs Host Disease / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004273:DNA, Neoplasm; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl