We observed that BK viremia was able to predict the risk of HC in haploidentical SCT. Moreover, HC severity correlated with quantitative BK viremia. The DAC-intensified conditioning regimen tended to result in a higher incidence of BK viremia; however, no other possible factors were identified. No correlation was found between BK and CMV or EBV infection, acute GVHD, and overall survival.
HC is believed to occur at a higher rate in haploidentical SCT than in fully matched related donors. In a study by Copelan et al., the incidence of HC was twofold greater in the haploidentical HCT setting than in the matched related donor HCT setting. The reported incidence of HC is approximately 30%, varying between 5.4% and 62.0%, after haploidentical SCT 7, 31, 32 33, 34. In our cohort, the frequency was 31.7% at a median of one-month post-SCT, which was consistent with previous reports.
HC is the result of the interplay of diverse elements, with BK reactivation being a key event in most cases. Several studies have examined the association between BK viremia or viruria with HC. Although considered to be less sensitive than BK viruria, BK viremia was more specific for the diagnosis of BK-related HC. BK viremia > 10,000 copies/ml had a sensitivity of 63% and specificity of 95% for diagnosing HC. Analysis of the association between HC and quantitative BK viremia showed that patients with a viral load > 104 copies/ml had a significantly higher risk of HC than those with a viral load of less than 104 copies/ml 22. Cesaro et al. prospectively observed that BK viremia > 1000 copies/ml had a sensitivity of 40% and a specificity of 93% for the detection of HC 35. Laskin et al. found that BK viremia of > 100 000 copies/ml had an adjusted HR of 116.8 for cystitis in children undergoing SCT 23. In the current study, the prevalence of BK viremia was 19.4%, similar to that reported by Yamada, in which the prevalence of BK viremia was 30% 36. Additionally, BK viremia at any level could significantly predict the occurrence of HC in haploidentical settings. More intensified conditioning regimens could be a risk factor for BK viremia because they may expose patients to agents that can cause damage to the bladder mucosa, such as radiation or medications that cause greater immunosuppression, resulting in viral reactivation 30. The present study showed that the more intense DAC preconditioning regimen could promote BK viremia.
Although BK viruria has been reported earlier and more frequently in SCT, BK viremia may serve as a more specific quantitative follow-up marker. In a pediatric study, a urine BK load > 107 copies/ml had a sensitivity of 86% and specificity of 60%, whereas a blood BK load > 103 copies/ml had a sensitivity of 100% and specificity of 86% for HC 35. The prognosis of BK viremia in patients with SCT remains uncertain. Haines et al. showed that patients with high BK viremia (> 10,000 copies/mL) experienced worse clinical outcomes than those with low BK viremia 37.
This study does have certain limitations. Data were obtained retrospectively through reviewing charts and are, therefore, susceptible to documentation errors or biases associated with more detailed documentation among patients with more visits. BK PCR, monitoring, and management were clinically dependent, non-routine, and non-serially collected. Therefore, further dynamic monitoring investigations are warranted.
In this study, the BK virus was closely related to the occurrence of HC, and infection with the BK virus has a very important predictive significance. Thus, prospective monitoring of BK viremia weekly during the first 100 days after allogeneic haploidentical SCT is necessary. Therefore, measures for the early identification of risk factors to prevent the progression of viral replication and infection are preferred. Further studies should be conducted to better monitor the trend of HC occurrence after transplantation, focusing on severe HC to guide medication monitoring.