Caspofungin for primary antifungal prophylaxis after T-cell-replete haploidentical stem cell transplantation with post-transplant cyclophosphamide

Eur J Haematol. 2019 Apr;102(4):357-367. doi: 10.1111/ejh.13214. Epub 2019 Feb 13.

Abstract

Objectives: T-cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is at high risk of invasive fungal infections (IFI), and anti-mold-active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting.

Methods: Here, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo-SCT. Caspofungin was administered only during the pre-engraftment phase.

Results: Hundred-day cumulative incidence of proven-probable IFI (PP-IFI) was 8.7% and median day of onset was 19 post-SCT. No patient died of PP-IFI, and overall survival (OS) and non-relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three-year overall survival (OS) and 1-year non-relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre-transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis.

Conclusion: In summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo-SCT with PT-Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections.

Keywords: caspofungin; haploidentical stem cell transplant; primary antifungal prophylaxis.

MeSH terms

  • Antibiotic Prophylaxis
  • Antifungal Agents / pharmacology*
  • Case-Control Studies
  • Caspofungin / pharmacology*
  • Cyclophosphamide / adverse effects*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Mycoses / etiology*
  • Mycoses / mortality
  • Mycoses / prevention & control*
  • Proportional Hazards Models

Substances

  • Antifungal Agents
  • Cyclophosphamide
  • Caspofungin