BK Virus Epidemiology, Risk Factors and Outcomes: A Retrospective Analysis of Hematopoietic Stem Cell Transplant Patients at Texas Children's Hospital

Abstract

Background. BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after pediatric Hematopoietic Stem Cell Transplant (HSCT). Limited data exist regarding the risk factors and treatment strategies for severe BKV-HC. Methods. We performed a retrospective review of HSCT patients at Texas Children's Hospital diagnosed with HC from 1 January 2011 to 31 December 2014. Results. Forty HSCT patients developed BKV-HC during the study period. The mean age was 10.9 years (2.1-20 years). Twenty-nine (72.5%) patients were male. Thirty-eight (95%) patients underwent allogenic HSCT (underlying diagnoses: leukemia (19), aplastic anemia/ myelodysplastic syndrome (9), primary immunodeficiency (4), hemoglobinopathy (3), lymphoma (2), and adrenoleukodystrophy). Two patients underwent autologous HSCT for high-risk neuroblastoma. BKV-HC occurred an average of 75 days after transplant (range 0-1222 days). The mean duration of HC was 175 days (2-1305 days). Patients required a total of 54 admissions for HC (0-4 admissions/patient). Mean peak serum creatinine associated with HC was 3.7 times baseline (range 1-14.7 times baseline). Seventeen patients had HC grade 4; 13 had HC grade 3. Seventeen patients (42.5%) required Foley placement to relieve urinary obstruction, 13 (32.5%) required continuous bladder irrigation, and 6 (15%) required nephrostomy tubes. All-cause mortality for patients with BKV-HC was 37.5%. The peak in creatinine above baseline was associated with duration of viremia (P = 0.03) but not viruria. Likewise, HC grades 3-4 were associated with peak viremia >10 000 (P = 0.02) but not peak viruria. Thirty-nine patients (98%) received fluoroquinolone (FQ) therapy, 15 (37.5%) received intravenous (IV) cidofovir, 13 (32.5%) received intravesicular cidofovir, and 5 (12.5%) received virus-specific cytotoxic T-lymphocytes (CTLs). For patients with grade 3-4 HC who survived >6 weeks after BKV-HC diagnosis, 6 of 21 (29%) had a partial or complete response to FQ, 7 of 9 (78%) to IV cidofovir, 8 of 11 (73%) to intravesicular cidofovir, and 4 of 4 (100%) to CTLs. Conclusion. Pediatric HSCT patients who develop BKV-HC experience significant morbidity. Peak and duration of viremia is associated with clinical outcome. Cidofovir therapy is associated with clinical response. New therapeutic modalities such as virus-specific CTLs might be a promising new intervention for pediatric HSCT patients with BKV-HC.