title: Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy.
abstract: The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect.
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@mte.biglobe.ne.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugiura
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Akiyama
authors.forename: Atsuo
authors.initials: A
authors.lastname: Maruta
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yujiri
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishii
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Hiroto
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010879:Piperazines / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl