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Malignancies in Wegener's Granulomatosis: Incidence and Relation to Cyclophosphamide Therapy in a Cohort of 293 Patients
MIKKEL FAURSCHOU, INGE JUUL SORENSEN, LENE MELLEMKJAER, ANNE GITTE RASMUSSEN LOFT, BJARNE SVALGAARD THOMSEN, NIELS TVEDE, and BO BASLUND
ABSTRACT. 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 (≤ 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 ≤ 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. Conclusion. 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. (First Release Oct 15 2007; J Rheumatol 2008;35:100-5) Key Indexing Terms:
WEGENER'S GRANULOMATOSIS
From the Department of Rheumatology, The National University Hospital, Rigshospitalet, Copenhagen; Department of Rheumatology, The University Hospital of Hvidovre, Copenhagen; Institute of Cancer Epidemiology, The Danish Cancer Society, Copenhagen; and Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark. M. Faurschou, MD, PhD, Department of Rheumatology, The National University Hospital, Rigshospitalet; I.J. Sorensen, MD, PhD, Department of Rheumatology, The University Hospital of Hvidovre; L. Mellemkjaer, PhD, Institute of Cancer Epidemiology, The Danish Cancer Society; A.G.R. Loft, MD, DMSci, Department of Rheumatology, Aarhus University Hospital; B.S. Thomsen, MD, DMSci, Department of Rheumatology, Aarhus University Hospital; N. Tvede, MD, Department of Rheumatology, The National University Hospital, Rigsho; B. Baslund, MD, PhD, Department of Rheumatology, The National University Hospital, Rigshospitalet. Address reprint requests to Dr. B. Baslund, Department of Rheumatology, 4242, The National University Hospital, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen OE, Denmark. E-mail: baslund@rh.dk. Accepted for publication July 18, 2007. |