Mucormycosis in adult hematopoietic stem cell transplant recipients during the antifungal prophylaxis era: a single-center retrospective case series

Background Mucormycosis is an uncommon but severe invasive fungal infection in hematopoietic stem cell transplant recipients. Contemporary cases may occur outside the classic early neutropenic post-transplant window and during antifungal prophylaxis. Methods We performed an International Classification of Diseases code-screened retrospective case series using the institutional denominator of adult hematopoietic stem cell transplant recipients at Mayo Clinic from January 1, 2008, through December 1, 2025. Cases were adjudicated using 2020 European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium criteria. We analyzed transplant characteristics, immune and pulmonary host factors, prophylaxis and therapeutic drug monitoring, diagnostic evidence, management, critical care use, and outcomes. Results Among 6,340 adult transplant recipients, 13 met criteria for invasive mucormycosis; eleven had allogeneic transplant and 2 had autologous transplant. Median age was 61 years, and median onset was 681 days after transplant. Underlying conditions included acute myeloid leukemia in 4 patients, chronic lymphocytic leukemia and chronic myeloid leukemia in 2 each, and diffuse large B-cell lymphoma, T-cell lymphoma, acute lymphoblastic leukemia, multiple myeloma, and VEXAS syndrome in one each. All patients were receiving systemic antifungal prophylaxis; 11 were receiving mold-active azoles and 6 were receiving posaconazole. Five patients had pre-diagnosis azole levels available. Neutropenia was present in 4 patients, while lymphopenia, low helper T-cell counts when measured, graft-versus-host disease, targeted or immunomodulatory therapies, and pulmonary host-defense abnormalities were frequent. Pulmonary or mixed pulmonary involvement occurred in 8 patients, disseminated disease in 3, and 9 cases were proven. Liposomal amphotericin B was used in 12 patients, source-control surgery in 6, intensive care unit admission in 6, mechanical ventilation in 5, and all-cause mortality was 5 of 13 at 30, 42, and 90 days. Conclusions This series describes mucormycosis in adult transplant recipients rather than establishing causal attribution to transplantation in every case. The findings support diagnostic vigilance for Mucorales infection in chronically immunocompromised transplant recipients, including those remote from transplant, receiving prophylaxis, and without neutropenia.