P1515: metagenomic next-generation sequencing based diagnosis of non-aspergillus mold infections in patients who received allogeneic hematopoietic stem cell transplantation: a single-center study

Topic: 22. Stem cell transplantation - Clinical Background: Non-Aspergillus mold infection (NAMI) is a rare invasive fungal infection in patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and noninvasive diagnostic options are limited. Aims: To analyze the clinical characteristics and overall survival (OS) of patients with NAMI using rapid pathogen detection through Metagenomic Next-Generation Sequencing(mNGS) of infected body fluids or tissues following allo-HSCT. Methods: We retrospectively studied 3098 patients who received allo-HSCT from January 1, 2019 to December 31, 2021 in Hebei Yanda Lu Daopei hospital. We summarized cases diagnosed with NAMI one month before allo-HSCT and after allo-HSCT, and analyzed the clinical characteristics and prognostic factors. Culture and mNGS were performed simultaneously to clarify the pathogen when the patient had clinical symptoms. Results: We identified 45 (1.45%) patients with proven or probable NAMI, 15(33.33%) of them had acute lymphoblastic leukemia, 19 (42.22%) had acute myeloid leukemia, 5 (11.11%) had aplastic anemia, and the remaining 6(13.33%) had other hematological disease. The median age was 26 (range:3-65) years. Thirty three(73.33%) patients underwent haploidentical Doner(HID)-HSCT, while 8(17.78%) received-Matched Unrelated Donor(MUD)-HSCT and 4(8.89%) underwent Matched Sibling Donor (MSD)-HSCT. Ten patients were diagnosed with NAMI one month before HSCT, and 35 patients were identified with NAMI after stem cell infusion. Pathogens included Rhizopus spp. (n=19), Fusarium spp. (n=9), Rhizomucor spp. (n=8), Absidia spp. (n=8), and Cunninghamella spp. (n=4). All pathogens were detected rapidly by mNGS, mainly from blood samples (n=34), and the rest from skin tissue(n=3), alveolar lavage fluid(n=3), sputum(n=2), nasal tissue(n=2), lung tissue(n=2), aqueous humor(n=2), intestinal tissue(n=1), pleural effusion(n=1), and cerebrospinal fluid(n=1). The median reads number was 210(range10-13748). Only 6 patients had positive blood cultures, 5 of whom were Fusarium. Pneumonia(62.22%) was the most common infection, following disseminated, intracranial, skin, sinuses, eye and intestinal lesions. For the 36 Mucorales-infected patients, 32 received combination therapy of liposome amphotericin B and Posaconazole including 6 of whom received surgical operation, and the remaining 4 received liposome amphotericin B or Posaconazole. Nineteen (52.78%) responded to therapy. For the 9 Fusarium-infected patients, 7 received combination therapy of liposome amphotericin B and Voriconazole including 1 with surgical operation, and the remaining 2 received Voriconazole. Only 2(22.22%) responded to therapy. The median follow-up time was 67(2-1240) days. The 2-year OS was (31.1±6.9)%, and the 2-year transplant-related mortality (TRM) was (41±7.5)%. After the diagnosis of NAMI, 31 patients died with a median time of 24(2-340) days from fungal infection (61.29%), relapse (16.1%), and graft-versus-host disease (GVHD,12.9%), respectively. Univariate analysis showed that infection involving the central nervous system (CNS, P=0.003), disseminated infection(P=0.027), GVHD (P<0.01), and without receiving surgical operation (P=0.032) were associated with a lower OS. Multivariate analysis confirmed that GVHD (P=0.03) was an adverse factor for OS. Summary/Conclusion: Patients with NAMI following allo-HSCT have a very poor prognosis. The major pathogen is Rhizopus. Traditional culture methods for pathogens are limited, and mNGS can quickly obtain evidence of pathogens. GVHD is an independent factor predicting inferior survival.Keywords: Fungal infection, HSCT, Hematopoietic cell transplantation