BK Virus Associated Hemorrhagic Cystitis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant

Hemorrhagic cystitis (HC) is a severe complication in pediatric and adult patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (HCT). HC is characterized by urothelial inflammation and painful hematuria which can be microscopic (Grade I) or macroscopic with blood clots and urinary tract obstruction (grade II-IV). The incidence of HC in pediatric HCT pts ranges from about 10% to 20 % and morbidity and mortality is as high as 75% depending on the severity of HC. The etiology of delayed onset of HC (greater than 2 weeks from conditioning therapy) is multifactorial, including damage from conditioning therapy, irradiation, graft-versus host disease (GVHD), steroids, and viral infection. Multiple viruses have been associated with HC, such as BK polyoma virus (BKV), CMV, and Adenovirus. Medical records of 30 pediatric pts who had undergone allogeneic or autologous HCT at our center between March of 2007 and April of 2010 have been reviewed. Urine of all patients was sent for quantitative BKV by PCR. BKV positive was considered as a load of ≥ 10E6 copies/ml. CMV was monitored quantitatively by PCR. Categorical tables were analyzed using Pearson's chi-square test and the Cochran-Mantel-Haenszel test. Tabular and graphical descriptive survival analyses were performed using cumulative incidence methods accounting for competing risks. Median age at transplant was 12.3 yrs. Nineteen pts had alternative donor HCT: 13 from a matched unrelated donor, 4 from double cord blood units (CBU) and 2 from a single CBU. Ten HCT were from matched related donors (MRD), including 1 with MRD CBU. One pt had an autologous transplant. All pts had received a full myeloablative conditioning therapy. Acute GVHD occurred in 28 pts (96.5%); all were treated with methylprednisolone at a median dose of 60mg daily. Out of 30 patients 10 (33.3%) patients had HC at a median of 37 days post HCT (range 24 to 73 days). Five (50%) had grade II HC, two pts (20%) had moderate grade III, and 3 (30%) had severe, grade IV HC. HC occurred in 2 of 12 (17%) BKV- pts compared with 8 of 18 (44%) BKV+ pts. (p = 0.11). One of 10 CMV-, BKV- pts (10%) pts had HC; compared to 5 of 15 (33%) of CMV+, BKV+ pts. (p = 0.18). The occurrence of severe HC was correlated with advanced disease state but not with higher steroid doses. BKV may play a role in HCT. A prospective study is needed to better identify the role of BKV and CMV in the development of HC.