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

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.

Figure 1

Cumulative incidence of invasive fungal infections (IFI) of patients receiving haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy): (A) day‐100 cumulative incidence of possible‐proven‐probable IFI of patients receiving caspofungin as primary antifungal prophylaxis; (B) day‐100 cumulative incidence of proven‐probable IFI of patients receiving caspofungin as primary antifungal prophylaxis; and (C) comparison of day‐100 cumulative incidence of proven‐probable IFI between patients receiving caspofungin or itraconazole as primary antifungal prophylaxis

Figure 2

Outcome of patients receiving haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy) and caspofungin as primary antifungal prophylaxis: (A) Kaplan‐Meier estimate of 3‐year overall survival; (B) 1‐year cumulative incidence of non‐relapse mortality; (C) 6‐month cumulative incidence of grade 2‐4 acute GVHD; and (D) 2‐year cumulative incidence of moderate‐severe chronic GVHD