Cytomegalovirus is a potential risk factor for late‐onset hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation

Abstract

Late-onset hemorrhagic cystitis (LOHC) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is primarily associated with viral infection. We prospectively quantified cytomegalovirus (CMV), BK virus (BKV), and adenovirus in urine and plasma using Q-RT-PCR in 50 consecutive patients to define the relationship between virus and LOHC. Of the 50 patients, 21 developed LOHC at a median of 29 days (range 4-64 days), with a cumulative incidence of 42% (67.1%). The cumulative incidence of LOHC on day 100 in patients with and without CMV viremia (prior to or at the onset of LOHC) were 56.3% (68.9%) and 16.7% (69.1%) (P 5 0.018), respectively, and it was 59.3% (69.8%) and 21.7% (68.8%) in patients with and without CMV viruria (prior to or at the onset of LOHC) (P 5 0.021), respectively. The cumulative incidence of LOHC was also higher in patients with a plasma BKV load increased 3 log 10 or with a urine BKV load increased 4 log 10 than those without the increase (P < 0.001). Only one patient with LOHC was tested positive for ADV. Both the univariate and multivariate analyses showed that CMV viremia (HR 5 3.461, 95% CI: 1.005-11.922, P 5 0.049) and a plasma BKV load that was increased 3 log 10 (HR 5 10.705, 95%CI: 2.469-46.420, P 5 0.002) were independent risk factors for the development of LOHC. We conclude that both CMV viremia and an increase of plasma BKV are independent risk factors for LOHC. And the role of CMV viremia was firstly demonstrated.

Intravesical cidofovir application in BK virus cystitis after allogeneic hematopoetic stem cell transplantation (HSCT) is safe and highly effective

“…Additional co-reactivations/infections with other viruses reflects the immunosuppressive status as known risk factor for BKPyV cystitis [11]. Accordingly, in our cohort 59% of the BKPyV cases also had CMV reactivation within the 1st 100 days, which is in line with findings by others showing that 59% of patients with CMV [12]. aGvHD is a known risk factor for viral reactions [13], which was also verified here, as 64% of all BKPyV cases suffered from aGvHD II-IV°and 73% received steroid-medication (≥5 mg/d) at the time of BKPyV cystitis.…”

Dynamics of BKPyV reactivation and risk of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

“…Several risk factors alone or in association with BKPyV have been reported to contribute to the development of HC, including GVHD, chemotherapeutics and supportive medications, and other bacterial or viral infections . In the present study, patients affected by HC showed a higher incidence of CMV reactivations (>1000 IU/mL), which has been previously correlated with BKPyV‐associated HC .…”

“…Fittingly, patients detected to be BKPyV positive in urine only did not develop clinical relevant HC. 15,30,[32][33][34][35][36] In the present study, patients affected by HC showed a higher incidence of CMV reactivations (>1000 IU/mL), which has been previously correlated with BKPyV-associated HC. 15 In line with the more protracted course of higher-grade HC (above) in conjunction with lymphocyte recovery and GVHD, patients with HC of grade II/III developed significantly more often GVHD after day+100 than those with low-grade HC.…”

Differential risk of viral infections in children undergoing complex anticancer therapy or hematopoietic stem cell transplantation

“…Age of the HCT recipient > 7 years is regarded as a risk factor for BKV reactivation [20]. CMV or human herpesvirus 6 (HHV6) viremia facilitates BKV hemorrhagic cystitis [21].…”