title: Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study.
abstract: The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather than autologous (17 of 348; 4.9%) HSCT and was significantly higher in patients receiving pre-emptive (18.6%) rather than empirical (6.1%) or targeted (9.5%) antifungal therapy (P = .002). Improvements in the selection and timing of prophylactic antifungals would be welcome. Health care providers should remain alert to the increased risk of IFD and associated mortality in allogeneic HSCT recipients and the ongoing risk of IFD even after discharge from the hospital.
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Nanfang Hospital, Nanfang Medical University, Guangzhou, China.
authors.forename: Fanyi
authors.initials: F
authors.lastname: Meng
authors.affiliation: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Han
authors.affiliation: Xinqiao Hospital, The Second Affiliated Hospital of Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Chinese PLA General Hospital (301 Hospital), Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.affiliation: The First Hospital of Peking University, Beijing, China.
authors.forename: Hanyun
authors.initials: H
authors.lastname: Ren
authors.affiliation: The First People's Hospital of Shanghai, Shanghai, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address: xjhrm@medmail.com.cn.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D002681:China; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology / Q000401:mortality; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D035781:Siblings; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D061349:Unrelated Donors
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014230:Triazoles
keywords: Allogeneic; Autologous; China; Fungal infection; Stem cells; Transplant