BK Polyoma Virus (BKV)-Associated Hemorrhagic Cystitis (HC) after Hematopoietic Stem Cell Transplantation (HSCT): Retrospective Evaluation of Epidemiology and Treatment

Background: The association of BKV with HC has been reported in allogenic HSCT recipients. However correlations between BKV load in the urine/blood and severity of HC and the efficacy of cidofovir (CDV) therapy for BKV are poorly defined.

Objective: A retrospective case-control study was performed to examine risk factors for severe BKV-HC, correlation of quantitative BKV DNA assays with clinical severity of HC, and the efficacy of CDV therapy in severe BKV-HC

Methods: Allogenic HSCT recipients transplanted from 2003-2008 who developed BKV-HC were enrolled. Fourteen patients with severe BKV-HC who required treatment with CDV (cases) were compared with 35 patients with non-severe BKV-HC not treated with CDV (controls). HC was defined as painful gross hematuria, standard grading was used for severity of HC. Risk factors evaluated included: age, source of hematopoietic stem cells [sibling donor (SD) vs. matched unrelated donor (MUD)], conditioning regimens, and presence of graft-vs-host-disease (GVHD). All patients with BKV-HC were initially managed with reduction of immunosuppression; CDV (1 mg/kg x 3 weekly doses) was initiated in severe BKV-HC cases

Results: Mean age of cases and controls were 49.7 vs 50.2 years, Karnosky’s and Charlson’s scores were 26.75 and 25.10 in cases vs 24.30 and 24.95 in controls. Source of donor cells in cases vs controls were: SD (36% vs 40%), MUD (43% vs 43%), mismatched (21% vs 17%). Conditioning regimens in cases vs controls were: busulfan (93% vs 74%) with fludarabine (93% vs 86%), thymoglobulin (21% vs 14%), tacrolimus (93% vs 97%), and mycophenolate (86% vs 80%). Neutropenia (50% vs 60%) and GVHD requiring corticosteroid therapy was noted in (79% cases vs 71%) controls prior to HC. Clinical manifestations of HC in cases vs controls: bladder spasms (86% vs 31%), hematuria (64% vs 69%), clot passage (50% vs 6%); Grade 3-5 HC (36% vs 14%). Median days for BKV appearance in urine after the HSCT in cases and controls were 43 and 65 days respectively. Median viruria levels were high in cases as compared to controls (remove this if no data is presented). BK viremia was found in 21% cases vs 14% controls. Steroids tapering (64% vs 60%) with tacrolimus dose change (43% vs 40%) were made in cases vs controls. 9/12 of cases responded to CDV with resolution of symptoms and viruria. Three of the cases and 2 control died <90 days of HSCT.

Conclusions: Severe BKV-HC was associated with more intense immunosuppression and early appearance of BK viruria. Severity of BKV-HC was reflected in higher frequency of bladder spasms, passage of clots, and was more often associated with BKV viremia. CDV therapy was effective in 75% of cases, but had no impact on mortality.