ASSOCIATION OF BK VIRUS WITH FAILURE OF PROPHYLAXIS AGAINST HEMORRHAGIC CYSTITIS FOLLOWING BONE-MARROW TRANSPLANTATION

Purpose: hemorrhagic cystitis (HC) after bone marrow transplantation ( BMT) has been ascribed to cyclophosphamide metabolites. HC has also be en associated with excretion of the BK type of polyomavirus. The relat ive contributions of cyclophosphamide metabolites and BK virus in the development of HC following BMT are unknown. Patients and Methods: We conducted a randomized trial to compare mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We studied the associat ion of BK virus with HC in 95 consecutive BMT recipients by prospectiv ely monitoring urinary excretion of BK virus using polymerase chain re action amplification of viral gene sequences. Results: HC occurred in 37 of 147 (25.2%) transplant recipients. the incidence of HC was simil ar in patients given mesna (26.8%, 19 of 71) or forced diuresis (23.7% , 18 of 76), and in recipients of allogeneic (27.2%, 18 of 64) or auto logous marrow (22.9%, 19 or 83). The incidence of HC was unrelated to primary disease, preparative regimen, or occurrence of graft-versus-ho st disease (GVHD). Excretion of BK virus was demonstrated in 50 BK vir uria (greater than or equal to two consecutive positive samples). HC o ccurred in 19 of 38 patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single urine sample positive for BK virus, an d in none of 45 who did not excrete BK virus (P < .0001). Shedding of BK virus also had a strong temporal correlation with onset of HC (r = .95). Conclusion: Mesna and forced diuresis are equally effective in a brogating the urothelial toxicity of preparative regimens for BMT. Sin ce HC after BMT is virtually always associated with persistent BK viru ria, strategies aimed at the prevention or elimination of viruria in B K seropositive recipients are warranted.