title: Use of azathioprine for graft-vs-host disease is the major risk for development of secondary malignancies after haematopoietic stem cell transplantation: a nationwide population-based study.
abstract: BACKGROUND
  As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors.
  
  
  METHODS
  We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM.
  
  
  RESULTS
  Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine.
  
  
  CONCLUSIONS
  This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Shipai Road, Section 2, Taipei 11217, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Chien
authors.affiliation: 1] Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Shipai Road, Section 2, Taipei 11217, Taiwan [2] Institute of Public Health, National Yang-Ming University, Taipei, Taiwan [3] School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: 1] School of Medicine, National Yang-Ming University, Taipei, Taiwan [2] Division of Hematology and Oncology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Hong
authors.affiliation: 1] School of Medicine, National Yang-Ming University, Taipei, Taiwan [2] Division of Oncology and Heamtology, Department of Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Teng
authors.affiliation: 1] Institute of Public Health, National Yang-Ming University, Taipei, Taiwan [2] School of Medicine, National Yang-Ming University, Taipei, Taiwan [3] Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Hu
authors.affiliation: 1] Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan [2] Department of information management, National Chung-Cheng University, Chiayi, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Shen
authors.affiliation: Department of Hematology and Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: F-C
authors.initials: FC
authors.lastname: Ku
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Shipai Road, Section 2, Taipei 11217, Taiwan.
authors.forename: S-C
authors.initials: SC
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: C-M
authors.initials: CM
authors.lastname: Yeh
authors.affiliation: 1] School of Medicine, National Yang-Ming University, Taipei, Taiwan [2] Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: T-J
authors.initials: TJ
authors.lastname: Chiou
authors.affiliation: 1] Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Shipai Road, Section 2, Taipei 11217, Taiwan [2] School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: J-P
authors.initials: JP
authors.lastname: Gau
authors.affiliation: 1] Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Shipai Road, Section 2, Taipei 11217, Taiwan [2] School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Tzeng
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors; D013624:Taiwan / Q000453:epidemiology; D019172:Transplantation Conditioning / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001379:Azathioprine