title: Administration of imatinib in the first 90 days after allogeneic hematopoietic cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.
abstract: BACKGROUND
  Relapse happens frequently after allogeneic hematopoietic cell transplantation (allo-HCT) in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Detection of the minimal residual disease (MRD) before and after allo-HCT is associated with higher relapse rate. Early administration of imatinib after allo-HCT may prevent recurrent Ph(+) ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after allo-HCT.
  
  
  METHODS
  Patients with Ph(+) ALL that underwent allo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the MRD (bcr-abl transcript levels). Imatinib therapy was initiated prior to 90 days after allo-HCT if the patient's absolute neutrophil count (ANC) was above 1.0 × 10(9)/L (without granulocyte colony-stimulating factor (G-CSF) administration) and the platelet count was greater than 50.0 × 10(9)/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were ≥ 10(-2) after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m(2) for children (younger than 17 years). Imatinib was administered for at least 1 month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission (CR(mol)) was sustained for at least 3 months.
  
  
  RESULTS
  From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years (range 6 - 50 years). Imatinib therapy was started at a median time of 60 days (range 20 - 122 days) post HCT (only one patient started Imatinib therapy at 122nd day after HCT). Twenty-five adult patients could tolerate a dose of 300 - 400 mg/d of imatinib, and three children tolerated a dose of 260 mg×m(-2)×d(-1). Sixty-eight percent of the patients experienced various adverse events during imatinib therapy, hematological toxicity being the most common adverse event. The median duration of imatinib treatment was 3 months (range 7 days-18 months). During the median follow-up of 24 months (range 16.0 - 54.5 months), 3 out of 27 patients that could be evaluated for efficacy died from relapse. The 3-year probability of relapse for the evaluated patients was (11.3 ± 0.61)%. The relapse rates among the subgroup of positive and negative bcr-abl patients before allo-HCT were 13.6% and 0, respectively (P > 0.05). The relapse rates among the subgroups of bcr-abl positive and negative patients after allo-HCT were 20.0% and 5.9%, respectively (P > 0.05). The relapse rates among the patients in first complete remission (CR(1)) and second complete remission/non-remission (CR(2)/NR) before transplantation were 0 and 31.4%, respectively (P < 0.05). The 3-year probability of overall survival (OS) and disease-free survival (DFS) for the all enrolled patients were (75.3 ± 8.1)%. The 3-year probabilities for OS and DFS among the subgroup of patients in CR(1) and CR(2)/NR before transplantation were (87.7 ± 8.2)% and (54.6 ± 15.0)%, respectively (P < 0.05).
  
  
  CONCLUSIONS
  Administration of imatinib at a dose of 300 - 400 mg/d in the first 90 days after allo-HCT is feasible in Ph(+) ALL patients. With this treatment, bcr-abl positive patients before or after transplantation do not have a higher relapse rate after allo-HCT compared with the bcr-abl negative patients. Because of lower relapse rate and better OS and DFS, we recommend that Ph(+) ALL patients receive allo-HCT in CR₁.
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.forename: Dai-Hong
authors.initials: DH
authors.lastname: Liu
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhan
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy*; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000379:methods*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate