Incidence, risk factors, and outcomes of BK hemorrhagic cystitis in hematopoietic stem cell transplantation from HLA-matched and haploidentical donors with post-transplant cyclophosphamide

Background: BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes.

Objectives: This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes.

Study design: Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used prophylactically with PTCy.

Results: The incidence of grade 2-4 BK-HC was 23%, with a higher prevalence of grades 3-4 in HAPLO (19%), compared to MSD (11%) and MUD (8%) recipients (p=0.02). BK-HC was diagnosed at a median of 29 days after HSCT and symptoms persisted for a median of 27 days, with longer duration in grade 3-4 cases (p=0.02). Additionally, higher grades were associated with a greater transfusion burden (p<0.001). JC virus coinfection was detected in 24%, and cytomegalovirus viruria in 17%, which was not treated. BK antiviral treatment beyond supportive care was used in only two patients, while antibacterial treatments were prescribed in 28% for urinary symptoms and in 57% for concomitant infections in other sites. Younger age and HAPLO donors were significant risk factors for developing higher-grade BK-HC. No interaction was seen between age and conditioning intensity. Importantly, BK-HC did not significantly impact overall survival or graft-versus-host disease-free relapse-free survival as a time-dependent variable, as well as non-relapse mortality. Furthermore, BK-HC patients maintained stable creatinine renal clearance at 1 year post-transplant.

Conclusions: BK-HC is a relatively early frequent complication in allogeneic HSCT with PTCy, especially in HAPLO recipients, with symptoms typically lasting a median of three weeks. Supportive care remains the mainstay of treatment, while specific antiviral treatments are rarely needed. The role of cidofovir and concomitant CMV viruria treatment are yet to be established. Our findings suggest that BK-HC does not significantly impact transplant outcomes and renal function.