Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type

Abstract

BackgroundHemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis. Design and MethodsTo test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19-71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8). ResultsTwenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, P<0.001). ConclusionsHemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria.

Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

“…Hemorrhagic cystitis (HC) may occur after HSCT either as early-onset disease due to conditioning toxicity, or late-onset disease associated with GVHD or viral infections such as BK virus, adenovirus, and cytomegalovirus (CMV) [4,5,6,7,8,9]. The incidence of HC after HSCT has been reported to range from 10 to 70%.…”

Mesenchymal Stromal Cells as an Adjuvant Treatment for Severe Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

“…Given the timing of its occurrence, HC can be divided into early onset (occurring within a few days after transplantation) and late onset (LO; occurring weeks later) subtypes, each with distinct pathogenetic factors. Early-onset HC mainly results from uroepithelial injury induced by chemotherapy/irradiation during conditioning, while LO-HC is frequently associated with viral infection and ongoing acute graft-versus-host disease (GVHD) [3,4,5]. …”

Evaluation and Management of BK Virus-Associated Nephropathy Following Allogeneic Hematopoietic Cell Transplantation

“…Hemorrhagic cystitis is commonly associated with BK infection, occurring in 10% to 25% of recipients [8,15], although a direct correlation for BK viruria and hemorrhagic cystitis has not been established. In fact, in a multivariate analysis for predictors of hemorrhagic cystitis in patients receiving HCT at M. D. Anderson, the presence of BK viruria was not found to be a significant factor [17]. …”

“…Development of BK viruria and associated nephropathies, including hemorrhagic cystitis, is dependent on several factors including type of conditioning regimen, use of T cell-depleted grafts, and use of related or unrelated donor grafts [17,18]. Leung et al suggested 3 phases for the development of BK virus hemorrhagic cystitis [19].…”