Sequential systematic anti-mold prophylaxis with micafungin and voriconazole results in very low incidence of invasive mold infections in patients undergoing allogeneic hematopoietic stem cell transplantation

Transpl Infect Dis. 2018 Aug;20(4):e12897. doi: 10.1111/tid.12897. Epub 2018 May 7.

Abstract

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk for invasive mold infections (IMI). The goal of the study is to describe the incidence and outcome of IMI in patients after allo-HSCT in a large cohort of patients receiving anti-mold prophylaxis. We conducted a retrospective review of 988 consecutive adults who underwent allo-HSCT in our center from 2008 through 2014. Standard prophylaxis consisted of micafungin 150 mg IV daily from admission to day +7 ± 3 followed by voriconazole until day +75 to +100. Cases meeting criteria for proven or probable IMI according to EORTC-MSG criteria were included. Median age at HSCT was 54 years. The most common diagnoses were acute myeloid leukemia (n = 351, 36%) and lymphoid malignancies (n = 248, 25%). Matched related or unrelated donors (URD) were used in 686 (69%) patients, mismatched URD in 142 (14%) and cord blood units in 154 (16%). Twenty-one patients were diagnosed with IMI after allo-HSCT, 19 probable and 2 proven, and one patient was diagnosed postmortem. Microbiological diagnosis was established in 9 cases, 5 of them being Aspergillus. One-year cumulative incidence (CI) of IMI was 1.6% (95% CI 0.9-2.5) while 12-week overall survival after IMI was 39% (95% CI 24-65) Analyzed by disease, there was a trend for a higher 1-year CI of IMI in patients with ALL (5% [95% CI 1.6-11.4]) when compared with AML (1.4%), MDS (1.5%) and lymphoma (1.2%), P = .06. The 1-year CI of IMI after transplantation is low in patients receiving anti-mold prophylaxis with micafungin bridged to voriconazole, although these infections are associated with a higher risk of mortality.

Keywords: allogeneic hematopoietic stem cell transplantation; antifungal; invasive fungal infection; molds.

MeSH terms

  • Adult
  • Aged
  • Antibiotic Prophylaxis / methods*
  • Antifungal Agents / therapeutic use*
  • Echinocandins / therapeutic use
  • Female
  • Fungi / isolation & purification*
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / surgery
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Incidence
  • Invasive Fungal Infections / epidemiology*
  • Invasive Fungal Infections / microbiology
  • Invasive Fungal Infections / prevention & control
  • Lipopeptides / therapeutic use
  • Male
  • Micafungin
  • Middle Aged
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects
  • Treatment Outcome
  • Voriconazole / therapeutic use
  • Young Adult

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Voriconazole
  • Micafungin