Background/Purpose: Cyclophosphamide (CYC) remains an important treatment option for Behçet’s syndrome (BS) pts with life threatening conditions such as arterial aneurysms. However, several adverse events are associated with CYC treatment and this has led to increased use of biologic agents such as rituximab in other vasculitides. The aim of this study is to survey the outcome and short and long term adverse events with CYC use among BS pts.

Methods: We conducted a retrospective chart review of all BS patients treated with oral or intravenous CYC between 1972 and 2006.  Patients were called and a standard form was used for collecting demographic characteristics, indication for CYC use, the reason for the cessation of therapy, cumulative dose of CYC, short and long term adverse events and outcome.

Results: We evaluated 99 pts who had an available contact information. After a median follow up of 18 (12-26) yrs after the initiation of CYC therapy, 27 pts had died within a median follow-up of 4 (0-10) yrs, 13 were lost after a median follow-up of 2.5 (0-11) yrs, and 59 were reached. CYC was prescribed for vascular involvement in 62 pts, eye involvement in 24, central nervous system involvement in 2, both vascular and eye involvement in 8 and both vascular and central nervous system involvement in 2. The median duration of CYC use and cumulative dose of CYC were 16 (6-63) gr and 12 (3-26) mo respectively. The reasons for death among the pts were shown in Table.

Twelve pts experienced serious adverse events associated with short term CYC use and 1 of them died due to infection. Among these adverse events, hemorrhagic cystitis occurred in 3 pts, infections in 5, ischemic stroke, acute myocardial infarction, anaphylactic reaction and grand mal epileptic seizure in 1 patient each. CYC treatment was terminated due to refractory disease in 30 pts and adverse events in 13. CYC induction was completed with beneficial results in the remaining 56 pts. During long term follow-up, malignancies and/or cardiovascular disease occurred in 27% of the pts. Overall, 9 malignancies were observed in 8 pts after a median follow up of 20 (12-25) yrs. The malignancies were t-MDS-AML, bladder carcinoma (n=2), lymphoma (n=2), HCC, colon adenocarcinoma, squamous cell carcinoma and prostate adenocarcinoma. Sixteen pts had cardiovascular disease and 3 had stroke.

Conclusion: CYC treatment was effective in about half of the pts. Serious adverse events including infections and malignancies occurred in 12% of the pts during CYC treatment and malignancies and cardiovascular events in 27% of the pts during long term follow-up. Other immunosuppressives used by these pts may also have contributed to these results and concomitant use of high dose corticosteroids may be responsible for the cardiovascular events. These results underline the need for safer and effective alternatives to CYC for serious organ involvement in BS, similar to that in other vasculitides.