Cytomegalovirus Viremia Is a Risk Factor for Late-Onset Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation

Purpose: Late-onset hemorrhagic cystitis (LOHC) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), which was mainly associated with BK virus and adenovirus (ADV). However, there still some patients developed LOHC without infection of BKV and ADV. Several retrospective studies showed that CMV infection was associated with LOHC. So, we design this prospective study to define the relationship between CMV infection and LOHC.

Design and Methods: Fifty consecutive patients who received allo-HSCT between October 2011 and December 2011 were prospectively investigated to screen BKV, ADV and CMV in the urine and plasma using Real-time Polymerase Chain Reaction (RT-PCR).

Results: Twenty-one out of the 50 patients developed LOHC with a cumulative incidence of 42%±7.1%.The median time from transplantation to onset of LOHC was 29 (range, 4-64) days. There are 34 patients and 21 patients developed CMV viremia and CMV viruria, respectively, within day 100. The cumulative incidence of LOHC in patients with CMV viremia was significantly higher than those without CMV viremia (58.8% vs. 6.3%, P=0.001) on day 100 after transplantation. Patients with CMV viruria had a significant higher cumulative incidence of LOHC than those without CMV viruria (60.7% vs. 18.2%, P=0.006). The cumulative incidence of CMV viremia and CMV viruria in patients with LOHC (n=21) versus those without LOHC (n=29) were 95.2% vs. 48.3% (P=0.001) and 80.9% vs. 34.5% (P=0.001), respectively. The cumulative incidence of LOHC in patients whose plasma BKV load increased more than or equal to 10³-fold over baseline was significantly higher than those with plasma load increase less than 10³-fold (67.9%±9.2%vs. 9.1%±6.3%, P<0.001). The cumulative incidence of LOHC in patients whose urine BKV load increased more than or equal to 10⁴-fold over baseline was significantly higher than those with urine load increase less than 10⁴-fold (66.7% ±10.3% vs. 19.2%±7.9%, P=0.002). ADV was positive in 4 patients including one patient with LOHC. Multivirariate analysis showed that CMV viremia (HR=10.496, 95% CI: 1.527-86.570, p=0.018) and plasma BKV load increased more than or equal to 10³-fold compared to baseline level (HR=10.669, 95% CI: 2.452-46.419, p=0.002) were two independent risk factors for LOHC.

Conclusion: Our data suggest that CMV viremia is a risk factor for LOHC following allo-HSCT.