Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation

Abstract

Acute pulmonary dysfunction remains a frequent and severe complication of hematopoietic stem cell transplantation (SCT). Almost half of the pulmonary insults that occur in this seating are noninfectious in origin and are referred to as idiopathic pneumonia syndrome (IPS). In this series of 3 patients, etanercept (Enbrel; Immunex, Seattle, WA), a soluble, dimeric tumor necrosis factor alpha-binding protein, was administered to 3 consecutive pediatric allogeneic BMT recipients with IPS. The administration of etanercept, in combination with standard immunosuppressive therapy, was well tolerated and associated with significant improvements in pulmonary dysfunction within the first week of therapy. These data suggest that etanercept may represent a safe, non-cross-reactive, therapeutic option for patients with IPS and that clinical trials studying etanercept for this indication are warranted.

Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease?

“…6 A recent review from the University of Michigan Medical Center demonstrated that the frequency of IPS after allogeneic SCT ranged from 5 to 25% depending upon the donor source and the degree of antigenic mismatch between donor and recipient. 12 The median time for development of IPS at Michigan was 14 days after transplant, and the overall day 100 mortality was 80%. Of note, the median time to death from diagnosis of IPS was 13 days despite aggressive treatment with highdose steroids and broad-spectrum antimicrobial therapy.…”

“…Of note, the median time to death from diagnosis of IPS was 13 days despite aggressive treatment with highdose steroids and broad-spectrum antimicrobial therapy. 12 The definition of IPS encompasses various forms of pulmonary toxicity (Table 3). In one small subset of patients with IPS, acute pulmonary hemorrhage or hemorrhagic alveolitis occurs.…”

“…29,30 Etiology of IPS As shown in Table 5, potential etiologies for IPS are several and include direct toxic effects of SCT conditioning regimens, occult pulmonary infections and the release of inflammatory cytokines that have been implicated in other forms of pulmonary injury. [31][32][33][34][35] Other immunologic factors may also be important as suggested by the association of Table 4 Risk factors for idiopathic pneumonia syndrome GVHD prophylaxis (methotrexate) 3 Acute GVHD (grades II-IV) 2,25 Acute GVHD (grade IV) 3,6 Increasing recipient age (X21 years) 3,25 (440 years) 28 Total body irradiation (TBI) X1200 cGy 2,3,28 ; dose rate of TBI (X6 Cgy/min) 3 Myeloablative conditioning High-dose 1-3 bis chloroethyl-1 nitrosurea 25 Decreased pre-transplant performance status 3 Longer duration from diagnosis to transplant 3 Transplantation for malignancy other than leukemia 6 Transplantation for hematologic malignancy 9 HLA disparity (donor:recipient) 12 IPS and severe GVHD in several large series. 2,3,[5][6][7]11 Moreover acute GVHD often precedes IPS, suggesting a possible causal relationship between the two disorders.…”

“…42 Lung injury correlated with the presence but not the severity of GVHD in that study, consistent with clinical reports of IPS in allogeneic SCT recipients whose signs and symptoms of GVHD were mild or absent. 12,[52][53][54][55][56] The inflammatory effectors TNFa and lipopolysaccharide (LPS)…”

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

“…25,28,32 In addition, etanercept has been successfully used in prevention of experimental GVHD-associated pulmonary complications and might be effective in the treatment of idiopathic pneumonia syndrome in patients. 33,34 We present data of a phase II study combining daclizumab with etanercept, aiming to increase response rates in steroid-refractory aGVHD without increasing infection related mortality.…”