BK Virus Induced Haemorrhagic Cystitis in Haematopoietic Stem Cell Transplant Setting — a 10 Year Retrospective Case Control Study

INTRODUCTION: BK virus (BKV) is a human polyomavirus that usually causes asymptomatic or mild respiratory illness in childhood and thereafter remains latent in renal epithelial cells. With decreased cell-mediated immunity, reactivation of BKV causing haemorrhagic cystitis (HC) is a well-known complication of haematopoietic stem cell transplantation (HSCT) that is associated with increased morbidity, mortality, longer hospital stays and increased hospital costs. This analysis was done to ascertain etiological risk factors, incidence and outcomes of BKV induced HC following HSCT.

METHODS: In this retrospective case control study of patients undergoing HSCT in the Department of Haematology at CMC Vellore between 2007 and 2016, we compared patients who developed BKV induced HC with those without BKV infection [controls] matched for age, diagnosis, conditioning regimen and donor source. Data was collected from individual medical records and databases maintained in the Departments of Haematology and Virology. The BKV PCR was designed as a real time PCR that targets the VP1 region of the BKV genome. Viral nucleic acid extraction was performed as recommended on the urine samples of these patients using the QIAamp DNA blood Mini kit (Qiagen, GMBH, Germany). Real-time PCR detection was performed as described previously.

RESULTS: There were 1276 (120 haploidentical) transplants that were performed between 2007 to 2016. Two hundred and sixty two (20.5%) patients had HC and BKV qualitative PCR was performed for 189 patients, of which 105 were positive. Among the cases, males were more affected and the median age was 20 years. The most common indication for transplant was aplastic anemia (31.4%), followed by acute myeloid (19.0%) and lymphoblastic (15.2%) leukemia. Predominant conditioning regimens were myeloablative conditioning (57.1%) with reduced intensity conditioning being least common (8.6%). In the patients with HC, Grade 3 HC was most commonly (57.1%) seen and the median time to development of HC was 35 (range 0-858) days. Specific treatment with cidofovir was given to only 5 patients, surgical intervention in 2 patients and foscarnet in 1 patient. Acute GVHD was seen in 53.35%. HLA matched sibling (53.3%) donors, followed by 8 or 9/10 matched unrelated (16.2%) donors were most frequent. Survival was significantly lower in the cases (42.9% vs 61%, p=0.013). Protective effect of non myeloablative conditioning, residual disease at time of transplant, lower CD34 dose, presence of acute GVHD and chronic GVHD, reactivation of CMV and presence of bacterial urinary tract infections (UTI) were significant factors on univariate analysis. Multivariate logistic regression confirmed presence of acute GVHD, bacterial UTI and residual disease at time of transplant as significant risk factors for BK viruria and disease.

CONCLUSION: BKV HC was seen in 8% of HSCT patients with mortality of 57.1%. Presence of acute GVHD, bacterial UTI and residual disease at time of transplant emerged as significant risk factors.