BK Virus-Associated Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation; Incidence and Risk Factors

Introduction:

Hemorrhagic cystitis (HC) is one of common complications after allogeneic hematopoietic SCT (HSCT) with reported incidence varying from 7 to 70%. Several reports have shown that BK is strongly associated with HC (BK-HC) following HSCT. We conducted an institutional retrospective study to analyze the incidence and clinical factors associated with BK-HC following HSCT.

Methods:

A total of 517 consecutive patients above the age of 14 years receiving HSCT from 2009 and June 2015 were included in this retrospective analysis and evaluated for HC and urinary BK. HC was defined as documented hematuria of any grade and BK viruria was defined as positive at any level by BKV quantitative PCR testing in urine.

Patients were stratified, based on hematuria and urinary BK virus, into the following groups (a) BK virus positive hemorrhagic cystitis (BK+HC), (b) BK virus negative hemorrhagic cystitis (BK-HC) and (c) Non-hemorrhagic cystitis (HC-). Screening for microscopic hematuria was performed only for patients with any kind of urinary symptoms.

Results:

479 patients (92.6%) were matched related donor and 308 (60%) were male with a median age of 24 (range 14 to 66). Diagnoses were AML for 195 (38%), ALL for 183 (35%) and bone marrow failure for 44 (8.5%). Conditioning regimen was cyclophosphamide based in 427 (82.6%) patients (97%) versus others in 90 (17.4%) patients. GVHD prophylaxis was CSA/MTX for 456 (88.4%) however, T cell depletion was used in 13%. Peripheral blood stem cells were used for 56% of patients.

With a median follow-up of 60 months for survivors (range 2 to 116.5 months), 43 (8%) patients showed BK+HC, 264 (51%) BK- HC while 209 (41%) did not have any hematuria (HC- group). Median time from transplantation to BK+ HC was 67 days (range 7 to 1261 days).

Univariate analysis for risk factors of BK+ HC showed male, use of T-cell depletion and AML diagnosis were statistically significant factors. Other factors like age, conditioning regimen, GVHD prophylaxis, stem cell source, mismatched and remission status were not statistically significant. BK+ HC group was associated with higher incidence of other infections like CMV viremia (p=0.01) and fungal infection (p<0.01). Incidence of acute GVHD was 62.8% in BK+ HC group, 43% in HC- BK and 33.3% in HC- group (p=<0.01), suggesting higher incidence of acute GVHD in BK+ HC group. There was no difference in incidence of chronic GVHD.

Conclusion:

Hematuria following allogeneic bone marrow transplantation occurs in almost half of patients (51%) while BK associated HC develops in 8% of patients. Factors associated with BK+ HC were male gender, use of T-cell depletion and AML diagnosis. BK+HC is usually associated with other infections like CMV viremia and fungal infections. Further studies are needed to minimize or prevent BK+ HC following HSCT especially in high risk group.