An evaluation of three methods used in the prophylaxis of cyclophosphamide-induced haemorrhagic cystitis in bone marrow transplant patients

Abstract

Background. Bone marrow transplant (BMT) recipi ents, who receive high-dose cyclophosphamide as part of conditioning therapy, are at considerable risk of developing haemorrhagic cystitis (HC). The role of prophylaxis of cyclophosphamide-induced HC is well- established in the literature, however, the literature is inconclusive with respect to the most effective form of prophylaxis. This study was undertaken to evaluate three methods of prophylaxis for HC used in BMT recipients in terms of the rate and severity of HC. The incidence and type of adverse effects attributed to each prophylactic regimen were also documented.

Method. A retrospective cohort study was con ducted in four teaching hospitals. During the 5-week data collection period, the medical records of 354 adult BMT patients were reviewed. Routine prophy laxis for cyclophosphamide-induced HC was used in all four hospitals. Three methods of prophylaxis were identified; bladder irrigation, forced diuresis, and Mesna.

Results. The incidence of HC (micro- and mac rohaematuria combined) was significantly higher in the hospital using bladder irrigation for prophylaxis than in the hospitals using Mesna or forced diuresis (P < 0.0001). The effect was more pronounced when the incidence of microhaematuria and macrohaema turia were compared separately. Patients receiving bladder irrigation for prophylaxis experienced an approximately threefold higher incidence of micro haematuria (35.4%) than patients receiving either Mesna or forced diuresis. The incidence of macroh aematuria in the bladder irrigation group was approx imately twice as high (21.1%) as in other methods. The difference in the incidence of HC between Mesna and forced diuresis was not statistically significant, with a reported incidence of microhaematuria of 9.6% and 8.9%, respectively, and for macrohaematuria of 13.2% and 8.9%, respectively. Logistic regression anal ysis was performed to examine the relationship be tween potential risk factors, methods of prophylaxis, and the incidence of HC. The final model included previous incidence of HC and graft failure during the current BMT. The most significant contributing factor was found to be the use of bladder irrigation for prophylaxis of HC (P = 0.001).

Conclusions. The results of this study suggest that the use of Mesna or forced diuresis for prophy laxis may reduce the incidence of cyclophosphamide- induced HC by approximately 20% compared with the 40% incidence in unprotected patients reported in the literature. Bladder irrigation was associated with a higher incidence of HC (57%), particularly in terms of microhaematuria. The findings suggest that bladder irrigation is the least effective method of prophylaxis and is possibly even a detrimental one because of the bladder trauma it induces. Mesna and forced diuresis appear to be more effective in pre venting the incidence of cyclophosphamide-induced HC, although, there is no clear difference in efficacy between these two methods.