Evaluation of risk for bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation with myeloablative conditioning regimens

Bone Marrow Transplant. 2024 Dec;59(12):1744-1753. doi: 10.1038/s41409-024-02422-z. Epub 2024 Sep 27.

Abstract

Bronchiolitis obliterans syndrome (BOS), as chronic manifestation of graft-versus-host disease (GVHD), is a debilitating complication leading to lung function deterioration in patients after allogeneic hematopoietic cell transplantation (allo-HCT). In the present study, we evaluated BOS development risk in patients after receiving myeloablative conditioning (MAC) regimens. We performed a retrospective analysis of patients undergoing allo-HCT, who received MAC with busulfan/cyclophosphamid (BuCy, n = 175) busulfan/fludarabin (FluBu4, n = 29) or thiotepa/busulfan/fludarabine (TBF MAC, n = 37). The prevalence of lung disease prior allo-HCT, smoking status, GvHD prophylaxis, HCT-CI score, EBMT risk score and GvHD incidence varied across the groups. The cumulative incidence of BOS using the NIH diagnosis consensus criteria at 2 years after allo-HCT was 8% in FluBu4, 23% in BuCy and 19% in TBF MAC (p = 0.07). In the multivariate analysis, we identified associated factors for time to BOS such as FEV1<median (99% of predicted) (HR = 2.39, p = 0.004), CMV patient serology positivity (HR = 2.11, p = 0.014), TLC < 80% of predicted (HR = 0.12, p = 0.02) and GvHD prophylaxis with in vivo T-cell depletion (HR = 0.29, p = 0.001) as predictors of BOS. In summary, we identified risk factors for BOS development in patients receiving MAC conditioning. These findings might serve to identify patients at risk, who might benefit from closely monitoring or early therapeutic interventions.

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Bronchiolitis Obliterans Syndrome
  • Bronchiolitis Obliterans* / etiology
  • Busulfan* / administration & dosage
  • Busulfan* / adverse effects
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myeloablative Agonists / adverse effects
  • Myeloablative Agonists / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Thiotepa / administration & dosage
  • Transplantation Conditioning* / adverse effects
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Busulfan
  • fludarabine
  • Vidarabine
  • Myeloablative Agonists
  • Cyclophosphamide
  • Thiotepa