title: Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis.
abstract: OBJECTIVE
  The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010.
  
  
  METHODS
  Cancer incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs).
  
  
  RESULTS
  The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non-melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow-up, with SIR estimates for these latency periods of 5.3 (95% CI 1.1, 15), 14.4 (95% CI 5.3, 31) and 10.5 (95% CI 1.2, 38), respectively. The incidence of myeloid leukaemia was significantly increased during years 5-9 [SIR 23.9 (95% CI 2.7, 86)]. Increased incidence of NMSC, bladder cancer and myeloid leukaemia was observed among patients exposed to cumulative CYC doses >36 g, while the only malignancy type observed in excess among those treated with lower CYC doses was NMSC. The cancer risk among CYC-naive patients was not significantly increased.
  
  
  CONCLUSIONS
  GPA patients experience a greater than expected number of specific malignancies following conventional therapies. Our analyses demonstrate a substantially increased risk of very late-occurring NMSC and bladder cancer in this patient group.
authors.affiliation: Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, mikkelf@dadlnet.dk.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Faurschou
authors.affiliation: Virus, Lifestyle, and Genes, Danish Cancer Society Research Center, Copenhagen.
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjaer
authors.affiliation: Department of Rheumatology, Odense University Hospital, Odense and.
authors.forename: Anne
authors.initials: A
authors.lastname: Voss
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kresten Krarup
authors.initials: KK
authors.lastname: Keller
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Ib Tonder
authors.initials: IT
authors.lastname: Hansen
authors.affiliation: Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet.
authors.forename: Bo
authors.initials: B
authors.lastname: Baslund
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use*; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D003520:Cyclophosphamide
keywords: bladder cancer; granulomatosis with polyangiitis; leukaemia; long-term follow-up; malignancy; non-melanoma skin cancer