title: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group.
abstract: OBJECTIVE
  A novel therapeutic approach is urgently needed for BCR-ABL-positive acute lymphoblastic leukemia (ALL). In this study, we assessed the efficacy and feasibility of chemotherapy combined with imatinib.
  
  
  METHODS
  A phase II study of imatinib-combined chemotherapy was conducted for newly diagnosed BCR-ABL-positive ALL in adults. Eighty patients were entered into the trial between September 2002 and January 2005.
  
  
  RESULTS
  Remission induction therapy resulted in complete remission (CR) in 77 patients (96.2%), resistant disease in one patient, and early death in two patients, as well as polymerase chain reaction negativity of bone marrow in 71.3%. The profile and incidence of severe toxicity were not different from those associated with our historic chemotherapy-alone regimen. Relapse occurred in 20 patients after median CR duration of 5.2 months. Allogeneic hematopoietic stem-cell transplantation (HSCT) was performed for 49 patients, 39 of whom underwent transplantation during their first CR. The 1-year event-free and overall survival (OS) rates were estimated to be 60.0%, and 76.1%, respectively, which were significantly better than those for our historic controls treated with chemotherapy alone (P < .0001 for both). Among the current trial patients, the probability for OS at 1 year was 73.3% for those who underwent allogeneic HSCT, and 84.8% for those who did not.
  
  
  CONCLUSIONS
  Our results demonstrated that imatinib-combined regimen is effective and feasible for newly diagnosed BCR-ABL-positive ALL. Despite a relatively short period of observation, a major potential of this treatment is recognized. Longer follow-up is required to determine its overall effect on survival.
authors.affiliation: Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. myanada@med.nagoya-u.ac.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Yanada
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugiura
authors.forename: Hideki
authors.initials: H
authors.lastname: Akiyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Maruta
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
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 / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D005240:Feasibility Studies; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D007564:Japan; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl