The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation.
Idiopathic pneumonia syndrome (IPS) refers to a diffuse, noninfectious, acute lung injury after hematopoietic stem cell transplantation. Historically, IPS is associated with respiratory failure and mortality rates exceeding 50%. Preclinical studies have implicated tumor necrosis factor-alpha as an important effector molecule in the development of disease. We studied the tumor necrosis factor-alpha inhibitor, etanercept, combined with corticosteroids in treating 15 patients (median age, 18 years; range, 1-60 years) with IPS. Eight of 15 patients required mechanical ventilation at therapy onset. Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (maximum 25 mg) twice weekly, for a maximum of 8 doses. Therapy was well tolerated with no infectious pulmonary complications noted. Ten of 15 patients had a complete response, defined as the ability to discontinue supplemental oxygen support during study therapy. The median time to complete response was 7 days (range, 3-18 days), with a day 28 survival of 73%. IPS onset was associated with elevations of several inflammatory proteins in the bronchoalveolar lavage fluid and plasma, and response to therapy correlated with reductions in pulmonary and systemic inflammation. The combination of etanercept and corticosteroids is safe and is associated with high response rates and improved survival in patients with IPS.
Yanik
Gregory A
GA
Department of Pediatrics, University of Michigan, Ann Arbor, USA. gyanik@umich.edu
Ho
Vincent T
VT
Levine
John E
JE
White
Eric S
ES
Braun
Thomas
T
Antin
Joseph H
JH
Whitfield
Joel
J
Custer
Joseph
J
Jones
Dawn
D
Ferrara
James L M
JL
Cooke
Kenneth R
KR
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000068800:Etanercept; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D013577:Syndrome; D014184:Transplantation, Homologous / Q000009:adverse effects*; D016896:Treatment Outcome
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept