Association between candidemia and non-infectious interstitial pneumonia after allogeneic hematopoietic cell transplantation: JSTCT Transplant Complications Working Group

Abstract Background α-Mannan from Candida albicans reportedly induces Th17-mediated pulmonary graft-versus-host disease (GVHD) in a mouse model. This study aimed to evaluate the association between candidemia and non-infectious interstitial pneumonia (IP) in allogeneic hematopoietic cell transplantation (HCT) recipients. Methods By using a Japanese transplant registry database, we analyzed 9,143 pediatric and adult patients with hematological malignancies who underwent their first (n = 7,531) or second (n = 1,612) allogeneic HCT between 2009 and 2019. Results Non-infectious IP was observed in 694 patients at a median of 63 days (range 0-1,292) after HCT. Candidemia occurred in 358 patients at a median of 31 days (range, 0-903 days) after HCT. Candidemia treated as a time-dependent covariate was significantly associated with an increased incidence of non-infectious IP (hazard ratio [HR], 2.51; 95%CI, 1.48-4.25) along with total body irradiation (> 8Gy) (HR, 1.57; 95%CI, 1.18-2.10) and malignant lymphoma (vs. acute myeloid leukemia) (HR, 1.30; 95%CI, 1.004-1.69). On the other hand, prompt platelet recovery (HR, 0.58; 95%CI, 0.45-0.75) and acute lymphoblastic leukemia (vs. acute myeloid leukemia) (HR, 0.68; 95%CI, 0.49-0.94) were associated with a reduced incidence of non-infectious IP. The median survival after the development of non-infectious IP in patients with prior candidemia was significantly shorter than that in those without it (22 days vs. 59 days, P < 0.001). Conclusions Candidemia was associated with an increased incidence of non-infectious IP. The prognosis of non-infectious IP after candidemia was extremely poor.