Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD and prior cyclophosphamide.

The frequency of haemorrhagic cystitis (HC) is evaluated in a paediatric population undergoing bone marrow transplantation (BMT) and its relationship to therapy with cyclophosphamide (CY) prior to conditioning for BMT (prior CY), infectious agents and graft-versus-host disease (GVHD) assessed. HC was defined as macroscopic haematuria with early onset HC occurring within 2 days of and delayed onset beyond 2 days from CY infusion. Sixty-three children received a total of 65 BMTs between July 1988 and January 1991, with 60 children receiving CY and 3 l/m2/24 h of post-hydration fluid post-CY as part of their conditioning. There were no cases of early onset HC. Eleven (17%) children had a total of 19 episodes of delayed onset HC. Overall, an infective agent was identified in the urine at the time of 17 of 19 (89%) episodes of HC. While papovavirus was the most common organism (12 episodes), adenovirus (2), cytomegalovirus (1) and bacteria (3) were also identified. The frequency of HC in transplants complicated by acute GVHD grade II-IV was 40% (p = 0.016), in children who had received prior CY was 43% (p < 0.001) and in mismatched transplants was 32% (p = 0.06). Four children who developed GVHD had exacerbations of symptoms associated with the use of high-dose steroid therapy. Our results suggest that most cases of delayed onset HC are temporally associated with an infective organism, predominantly papovavirus, and identify GVHD and prior CY as risk factors. Increased symptomatology was associated with acute GVHD and its treatment and this may be explained by the added immune suppression, resulting in greater viral reactivation and further mucosal damage.