The Characteristics of Hemorrhagic Cystitis After Allogeneic Stem Cell Transplantation, and Possible Predictive Value of Absolute Lymphocyte Count for Clinical Outcome.

Hemorrhagic cystitis (HC) after allogeneic stem cell transplantation (SCT) is a common complication associated with frequent prolongation of hospitalization and occasional death and yet, the observed risk and prognostic factors as well as the understanding of pathophysiology remain inconsistent. Recent evidences point to HC being triggered by reactivation of viral replication, mainly BK virus, implicating factors standing for recipients’ status of immunity may correlate with the incidence, severity and prognosis of HC.

We retrospectively investigated 450 adult patients who underwent allogeneic SCT from January 2007 through December 2009 in order to analyze the incidence, risk and prognostic factors of HC.

The median age was 38 years old (range, 15–70) and 90 % of the patients had malignant disease. Thirty-five percent of patient (n=159) had advanced disease status at transplantation. Two hundred thirty-nine patients (53%) and 211 (47%) had related and unrelated donors, respectively. Conditioning regimens consisted of myeloablative (n=266, 59%) and reduced-intensity regimens (n=184, 41%). With a median follow-up of 549 days (range, 83 – 1172), 58 patients developed HC (cumulative incidence, 13.2%±1.6%) and the median day of onset was 36 days after transplant (range, 1–441) consisting of pre-engraft (n=13) and post-engraft HC (n=45). Among 58 patients with HC, urine virus was detected in 54 patients. Thirty patients had positive PCR for BK virus and 19 patients were positive by JC virus PCR. Not all the patients with positive PCR results showed growth by urine culture. Eleven patients were BK virus culture positive and 7 patients showed growth of adenovirus. Four patients showed positive PCR results for both BK virus and JC virus. The overall severity of HC was as follows; grade I (19%), grade II (21%), grade III (47%), and grade IV (14%). On multivariate analyses, advanced disease status at transplantation [HR (95% CI), 1.81 (1.003-3.266), P-value=0.049] and concurrent acute graft-versus-host disease (GVHD) [HR (95% CI), 1.88 (1.013-6.487), P-value=0.046] were revealed to be significantly associated with the occurrence of HC. All patients with HC were initially treated with forced hydration and/or bladder irrigation, and cidofovir at 5 mg/kg/day for two consecutive weeks and biweekly thereafter was used in 18 patients with documented test results associated with BK virus showing no improvement within 7 days after treatment. In 4 cases of grade IV HC with urinary tract obstruction, double-J catheterization or percutaneous nephrostomy were performed. The overall complete response (CR) rate of HC patients was 72%. Notably, multivariate analyses showed that patients with absolute lymphocyte count over 1000/μL at onset of HC had significantly better outcome in the achievement of CR [HR (95% CI), 10.8 (1.16-100.81), P-value=0.036)].

This study demonstrates the incidence, risk and prognostic factors of 58 patients with HC, and the value of the absolute lymphocyte count at onset of HC as a prognostic predictor. Patients who have advanced disease status at transplantation or develop acute GVHD are at high risk of developing HC, and early monitoring should be implemented. Our data also indicates that replication of JC virus as well as BK virus may account for a considerable portion of etiologies of HC. Prospective trials on analyzing the risk and prognostic factors for HC are needed for the development of reliable tools for predicting HC, and the relation between degree of immune reconstitution or JC virus and the occurrence of HC after SCT should also be further investigated.

No relevant conflicts of interest to declare.