Anti-fungal prophylaxis for allogeneic stem cell transplants – pro
Lay Summary: A discussion of anti-fungal prophylaxis for allogeneic stem cell transplant recipients.
Candida spp. and Aspergillus spp. are the most important fungal pathogens contributing to significant morbidity and mortality in immunocompromised patients. Yeast infections are mainly caused by fungi colonizing the gastrointestinal tract, which overgrow under antibacterial treatment and subsequently invade tissue and blood vessels during neutropenia. All allogeneic stem cell recipients should receive anti-fungal prophylaxis; traditionally fluconazole to prevent systemic infection with susceptible yeasts during neutropenia. A recent study published the superiority of itraconazole over fluconazole. However, oral administration of itraconazole is sometimes limited by gastrointestinal side-effects (BI). Voriconazole is a more recent alternative. Overall, antifungal prophylaxis is recommended at least until day +75 post transplant. If immunosuppression is given after day +75, as it would be after an allogeneic transplant, longer antifungal prophylaxis should be considered. A recent data published in the New England Journal of Medicine showed a clear role of posaconazole in terms of being efficacious and safe and prolonging survival. Voriconazole, being less recent is less studied but is very similar. Based on NCCN IF-3, it can be approved for 75+ days in total, since he optimal duration of therapy is not known and guidelines that recommend prophylaxis are silent on it duration, except that 75+ days is stated .Voriconazole, being less recent is less studied but is very similar to other drugs of the same class and should be considered to be an accepted option.
A recent review concluded that included evidence-based guidelines recommended posaconazole as an alternative to voriconazole for salvage therapy of IA, and for the primary antifungal prophylaxis against IA in patients with AML or myelodysplastic syndrome, as well as HSCT recipients. The guidelines also suggest posaconazole prophylaxis as an alternative to fluconazole in patients at least 13 years of age with AML or myelodysplastic syndrome during chemotherapy, especially for those considered at higher risk for IA. Posaconazole may be considered in children at least 13 years of age with GVHD after allogeneic HSCT.
A recent review concluded that included evidence-based guidelines recommended posaconazole as an alternative to voriconazole for salvage therapy of IA, and for the primary antifungal prophylaxis against IA in patients with AML or myelodysplastic syndrome, as well as HSCT recipients. The guidelines also suggest posaconazole prophylaxis as an alternative to fluconazole in patients at least 13 years of age with AML or myelodysplastic syndrome during chemotherapy, especially for those considered at higher risk for IA. Posaconazole may be considered in children at least 13 years of age with GVHD after allogeneic HSCT.
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Ye, P., Pei, R., Hu, Y. et al. Posaconazole oral suspension for secondary antifungal prophylaxis in allogeneic stem cell transplantation recipients: a retrospective study. BMC Infect Dis 22, 465 (2022)
Posaconazole for the Prophylaxis and Treatment of Invasive Aspergillosis: A Review of Clinical Effectiveness and Guidelines2022, https://www.ncbi.nlm.nih.gov/books/NBK531401/ Accessed 3/8/2023
Posaconazole Prescribing Information 2023
V. David I., Marks et al for the IMPROVIT Study Group Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic haematopoietic stem-cell transplantation British Journal of Haematology Volume 155, Issue 3, pages 318–327, November 2011
W. H. Krüger et al, Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Oncology Annals of Oncology 2005 16(8):1381-1390;
G. Corrado Prophylaxis and Treatment of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Results of a Consensus Process by Gruppo Italiano Trapianto di Midollo Osseo (GITMO) Clin Infect Dis. (2009) 49 (8): 1226-1236.
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