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

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.

A Single-Center, Open-Label Trial of Isavuconazole Prophylaxis against Invasive Fungal Infection in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

“…In accordance with the institutional standard of care, HCT recipients received antifungal prophylaxis with micafungin 150 mg i.v. once daily from the day of admission for HCT until day +7 post-transplantation (D+7) [19,20]. The dose of micafungin was chosen based on early studies suggesting administration of high doses of micafungin when used for antimold prophylaxis [21,22].…”

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

“…35,[46][47][48] Therefore, because of the high risk of aspergillosis in these patients, prophylaxis with drugs such as caspofungin, micafungin, voriconazole, posaconazole, liposomal amphotericin B (LAMB), and caspofungin may be beneficial. [48][49][50] Noteworthy, depending on the patient's condition, these drugs can have different effects; however, side effects and toxicity of these drugs may limit their longterm use. 51 Fontana and his colleagues reported that, although isavuconazole was used for prophylaxis patients with hematologic malignancies or hematopoietic cell transplant recipients to prevent IFI, the results showed an increase in the rate of IFI, especially invasive pulmonary aspergillosis in these patients.…”

Treatment of invasive fungal diseases in cancer patients—Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…Voriconazole is inactive in mucormycosis, and breakthrough infections during voriconazole exposure have been reported from retrospective evaluations and various case reports 109,203‐206 . However, prospective clinical trials on voriconazole prophylaxis did not confirm an increased incidence 207‐209 …”