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Post-Transplant Complications

Efficacy and safety of micafungin for prophylaxis of invasive fungal infections in patients undergoing haplo-identical hematopoietic SCT

Bone Marrow Transplantation volume 48, pages 1472–1477 (2013)Cite this article

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Abstract

Invasive fungal infections (IFIs) such as candidiasis and mold infections have caused significant morbidity and mortality among immunocompromised patients in recent years. Micafungin, a new echinocandin, inhibits fungal cell wall β-glucan synthesis, with potent activity against most species of Candida and Aspergillus. The aim of this observational study was to investigate the efficacy and safety of micafungin in prophylaxis of IFIs in 26 high-risk adult patients with various hematological diseases receiving haplo-identical Allo-SCT. Only two patients had a history of possible aspergillosis before transplant treated by voriconazole. The patients received a median of four lines (2–7) of treatment before Allo-SCT. Thirteen patients (50%) received at least one prior Auto-SCT; and eight patients (31%) received a previous Allo-SCT. Patients received a median of 29 infusions (range, 15–85) of micafungin (50 mg/day i.v. as a 1-h infusion). The treatment was initiated at the beginning of the transplant conditioning regimen until the hospital discharge. None of our patients discontinued the treatment for drug-related adverse events. Micafungin was not associated with any hepatotoxicity. Only one patient (4%) discontinued the treatment because of early disease progression. In all patients no Candida and/or Aspergillus species was documented after 3 and 6 months from transplant. None of our patients presented a positive galactomannan antigenemia >0.5. Nine patients (35%) presented a CMV reactivation. Four patients presented an acute GVHD grade II and two patients presented a chronic GVHD. The median follow-up was 11 months (3–23). At the last follow-up, there were 20 patients (77%) who were alive; four patients (12%) died because of disease progression and two patients because of graft failure. Micafungin has a good safety and tolerability profile, with an efficacy in preventing IFI in this high-risk population. Our data provide support for an efficacy study in a prophylaxis setting, but prospective and comparative clinical trials using micafungin are urgently needed to define the role of this drug in prophylaxis after haplo-identical Allo-SCT.

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Acknowledgements

We thank the Association pour la Recherche sur le Cancer (ARC) (Pole ARECA) for their generous support of our research. Our group was supported by several grants from the French Ministry of Health as part of the Programme Hospitalier de Recherche Clinique (PHRC). We thank the nursing staff for providing excellent care for our patients and the physicians of the Hematology Department at the Institut Paoli-Calmettes for their important study contributions and dedicated patient care.

Author contributions: JE-C conceived and designed the study, collected and analyzed data, performed statistical analyses, provided clinical care, and wrote and revised the manuscript; GV and RC collected and analyzed data, performed statistical analyses, provided clinical care and revised the manuscript. SF, CF, CO, AG, DC, RB and NV provided clinical care and commented on the manuscript. SD and EF provided pharmaceuticals controls and commented on the manuscript. PBperformed microbiologic monitoring and controls, and commented on the manuscript. CC is in charge of the cell therapy facility that collected and delivered allogeneic blood cell grafts infused into patients included in this analysis, and commented on the manuscript. DB recruited patients, provided clinical care and commented on the manuscript.

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Authors and Affiliations

  1. Unité de Transplantation et de Thérapie Cellulaire (U2T), Institut Paoli-Calmettes, Marseille, France

    J El-Cheikh, G Venton, R Crocchiolo, S Fürst, C Faucher, A Granata, C Oudin & D Blaise

  2. Département d’Onco-Hématologie, Institut Paoli-Calmettes, Marseille, France

    J El-Cheikh, G Venton, R Crocchiolo, S Fürst, C Faucher, A Granata, C Oudin, D Coso, R Bouabdallah, N Vey & D Blaise

  3. Pharmacie Centrale, Institut Paoli-Calmettes, Marseille, France

    S Duran & E Fougereau

  4. Département de Microbiologie, Institut Paoli-Calmettes, Marseille, France

    P Berger

  5. Centre de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France

    C Chabannon

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  1. J El-Cheikh
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Correspondence to J El-Cheikh.

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El-Cheikh, J., Venton, G., Crocchiolo, R. et al. Efficacy and safety of micafungin for prophylaxis of invasive fungal infections in patients undergoing haplo-identical hematopoietic SCT. Bone Marrow Transplant 48, 1472–1477 (2013). https://doi.org/10.1038/bmt.2013.87

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