Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplantation and Post-Transplant Cyclophosphamide

Abstract

Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined.We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (PT-Cy).Overall, 99 patients were identified: 30 patients received micafungin, 50 and 19 patients received itraconazole and fluconazole, respectively. After a median follow-up of 12 months (range: 1–51), proven or probable IFIs were reported in 3 patients (10%) in the micafungin, 5 patients in the itraconazole (10%) and 2 patients (11%) in the fluconazole group (p=0.998). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 3 [6%] in the itraconazole vs. 2 [11%] in the fluconazole group, p=0.589). Four patients (13%) in the micafungin group vs 13 (26%) patients in the itraconazole group and 10 (53%) patients in the fluconazole received empirical antifungal therapy (P = 0.19).No serious adverse events related to treatment were reported by patients, and there was no treatment discontinuation because of drug-related adverse events in both groups.The present analysis shows that micafungin did better than fluconazole in preventing invasive aspergillosis after transplant in these high-risk hematological diseases, as expected. In addition, micafungin was more effective than itraconazole in preventing all IFI episodes when also considering possible fungal infections. Future prospective studies would shed light on this issue, concerning this increasingly used transplant platform.

Prospective Evaluation of Infection Episodes in Cancer Patients in a Tertiary Care Academic Center: Microbiological Features and Risk Factors for Mortality

“…There are some reports showing azole-resistant breakthrough fungemia, but a recent study from the EORTC revealed that antifungal prophylaxis was protective in fungemia in cancer patients [39]. As there are various studies on different oral antifungal prophylaxes with different outcomes favoring posaconazole, itraconazole, or fluconazole use in high-risk patients, further studies are required about which drug to use for which patient and how long these drugs must be used [40,41,42]. …”

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients

“…It has been compared to posaconazole in patients with acute leukaemias and myelodysplastic syndromes on induction treatment in a randomised study, proving to be a safe prophylactic alternative in this type of patients [28]. It has also been compared to fluconazole and traconozole in patients undergoing haploidentical transplantation, presenting good efficacy [29]. We also have data from a meta-analysis performed with 1,049 cases and 959 controls, confirming that micafungin had a significantly higher treatment success rate than the other antifungals, with a better secure profile [30].…”

Fluconazole is as effective as other anti-mold agents in preventing early invasive fungal disease after allogeneic stem cell transplantation: assessment of antifungal therapy in haematological disease in China

“…The GITMO guidelines ( 19 ) recommend an anti-mold agent for such patients, but the evidence supporting this recommendation is not strong. A small retrospective study ( 27 ) from France compared micafungin, fluconazole, and itraconazole in 99 patients who underwent haplo-identical HSCT and received post-transplant cyclophosphamide. As expected, the results demonstrated micafungin had better efficacy than fluconazole in preventing invasive aspergillosis in these patients.…”