title: Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.
abstract: This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses.
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan; Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Matsumura-Kimoto
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan. Electronic address: yinamoto@ncc.go.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Inamoto
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kinuko
authors.initials: K
authors.lastname: Tajima
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kawajiri
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Hirakawa
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ino
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Asao
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tamogami
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Kono
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Takeda
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Okinaka
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Blood Transfusion and Cellular Therapy, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000150:complications* / Q000188:drug therapy* / Q000209:etiology; D016946:Gram-Negative Aerobic Rods and Cocci; D016905:Gram-Negative Bacterial Infections / Q000139:chemically induced / Q000382:microbiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000139:chemically induced; D013997:Time Factors; D014184:Transplantation, Homologous; D014777:Virus Diseases / Q000139:chemically induced; D055815:Young Adult
chemical_list: D005938:Glucocorticoids
keywords: Adenovirus; Cytomegalovirus; Fungal infection; Graft-versus-host disease; Hematopoietic cell transplantation; Steroid dose