Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Incidence, epidemiology, and risk factors of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can vary from different cohorts and countries. Therefore, we performed a nationwide study to establish a proper antifungal prophylaxis strategies based on risk stratifications of IFDs after all-HSCT in Korea (RISK study). This was a multicenter, retrospective, and observational study in Korea. All consecutive adult patients who received allo-HSCT in 2013 were included. The 12-month cumulative incidence of proven/probable IFDs (PP-IFDs) was calculated during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT. Cox proportional hazard regression analysis was performed to identify risk factors for PP-IFDs at each phase. A total 521 allo-HSCT cases in 518 patients were analyzed. Overall cumulative incidence of PP-IFDs were 4.09% (95% confidence interval [CI], 2.38 to 5.81), 7.38% (95% CI, 5.09 to 9.67), and 15.36% (95% CI, 12.04 to 18.68) at the early, late and very phases, respectively. In multiple Cox regression analysis, variables were associated with PP-IFDs in each period were identified. Variables associated with early phase include underlying pulmonary diseases, underlying nonmalignant stable or chronic disease at allo-HSCT, unrelated or family mismatched donor, and prolonged neutropenia. Variables associated with the late phase include high ferritin level at the time point of allo-HSCT, use of secondary immunosuppressive agents due to refractory graft-versus-host disease (GVHD), and cytomegalovirus reactivation. For the very late phase, variables were secondary neutropenia, severe chronic GVHD, and use of TNF-alpha inhibitor for refractory GVHD. This study revealed the high cumulative incidence of IFDs in Korean allo-HSCT recipients, which have distinct risk factors in each phase after allo-HSCT. Our findings indicate that tailored antifungal prophylaxis is necessary for high-risk patients. Clinicians should consider using mold-active antifungal prophylaxis in allo-HSCT recipients who have high risks at different treatment period.