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

Abstract

Background: Hemorrhagic 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 methods: To 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).

Results: Twenty-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).

Conclusions: Hemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria.

Figure 1.

Polyoma viruria and hemorrhagic cystitis during the first 60 days after transplant. Median time to cystitis was 49 days (n=168 on day 60).

Figure 2.

(A) Cumulative incidence of hemorrhagic cystitis as a function of donor type. Recipients of haploidentical (haplo) and cord blood (CB) transplants had a higher incidence of hemorrhagic cystitis than recipients of unrelated bone marrow or peripheral blood transplants. (B) Cumulative incidence of hemorrhagic cystitis as a function of conditioning regimen intensity. (C) High cumulative incidence of hemorrhagic cystitis in recipients of ablative haploidentical (haplo) or cord blood (cord) transplants who had BK viruria (+ve) prior to transplant, when compared to recipients of unrelated donor (UD) transplants (PCR +ve or PCR negative –ve).