Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients.
OBJECTIVE
To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG.


METHODS
In total, 293 patients diagnosed with WG between 1973 and 1999 were studied. Cancer incidence in the cohort was assessed through 2003 by linkage to the Danish Cancer Registry and compared to that of the general population by calculation of standardized incidence ratios (SIR). Analyses were stratified according to treatment with low cumulative CYC doses (< or = 36 g) and high doses (> 36 g, corresponding to treatment with 100 mg CYC/day for > 1 year).


RESULTS
Fifty cancers occurred during 2121 person-years of followup (SIR of cancer of 2.1, 95% CI 1.5-2.7). Significantly increased SIR were observed for acute myeloid leukemia (AML; SIR 19.6, 95% CI 4.0-57), bladder cancer (SIR 3.6, 95% CI 1.2-8.3), and non-melanoma skin cancers (SIR 4.7, 95% CI 2.8-7.3). Leukemias and bladder cancers were diagnosed 6.9-18.5 years after initiation of CYC therapy. The risk of these malignancies was not increased for patients who never received CYC or for patients treated with cumulative CYC doses < or = 36 g. In contrast, high risks of AML (SIR 59.0, 95% CI 12-172) and bladder cancer (SIR 9.5, 95% CI 2.6-24) were observed for patients treated with cumulative CYC doses > 36 g.


CONCLUSIONS
Treatment with high cumulative CYC doses implies a substantial risk of late-occurring, serious malignancies in WG. Patients with WG should be monitored for development of cancer for several decades after cessation of CYC therapy. These findings emphasize the need for development of new treatment regimens in WG.
Faurschou
Mikkel
M
Department of Rheumatology, The National University Hospital, Rigshospitalet, Copenhagen, Denmark.
Sorensen
Inge Juul
IJ
Mellemkjaer
Lene
L
Loft
Anne Gitte Rasmussen
AG
Thomsen
Bjarne Svalgaard
BS
Tvede
Niels
N
Baslund
Bo
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D003718:Denmark / Q000453:epidemiology; 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; D009153:Mutagens / Q000008:administration & dosage / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*
D018501:Antirheumatic Agents; D009153:Mutagens; D003520:Cyclophosphamide