Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy

Eur J Haematol. 2024 Apr;112(4):577-584. doi: 10.1111/ejh.14147. Epub 2024 Jan 6.

Abstract

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.

Keywords: CMV; allogeneic hematopoietic stem cell transplantation; hemorrhagic cystitis; letermovir.

MeSH terms

  • Acetates*
  • Alkylating Agents
  • Cystitis* / diagnosis
  • Cystitis* / epidemiology
  • Cystitis* / etiology
  • Cystitis, Hemorrhagic*
  • Cytomegalovirus
  • Cytomegalovirus Infections* / diagnosis
  • Cytomegalovirus Infections* / epidemiology
  • Cytomegalovirus Infections* / etiology
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Male
  • Quinazolines*
  • Retrospective Studies
  • Risk Factors

Substances

  • letermovir
  • Alkylating Agents
  • Acetates
  • Quinazolines