Risk factors for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis

Objective and Background: BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients. Methods: We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC. Results: Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I2 = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I2 = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I2 = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I2 = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I2 = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I2 = 79%) were significantly associated with BKV-HC in the univariable analysis. Conclusions: Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.