Inflammatory cytokines and the development of pulmonary complications after allogeneic hematopoietic cell transplantation in patients with inherited metabolic storage disorders

Sandhya Kharbanda, Angela Panoskaltsis-Mortari, Imad Y. Haddad, Bruce R. Blazar, Paul J. Orchard, David N. Cornfield, Satkiran S. Grewal, Charles Peters, Warren E. Regelmann, Carlos E. Milla, K. Scott Baker

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Patients with inherited metabolic storage disorders are at a higher risk of developing pulmonary complications after hematopoietic cell transplantation (HCT). This single-center prospective study of 48 consecutive inherited metabolic storage disorder patients was performed to identify risk factors for the development of pulmonary complications after HCT. Before HCT, subjects underwent bronchoalveolar lavage (BAL) for cell count, culture, nitrite levels, and analysis of proinflammatory cytokines and chemokines. The overall incidence of pulmonary complications was 52% (infectious, 23%; noninfectious, 29%) over a period of 4 years. Diffuse alveolar hemorrhage was the most frequent noninfectious complication and occurred in 19% of patients, all of whom had a diagnosis of mucopolysaccharidosis (Hurler and Maroteaux-Lamy syndromes). Levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor α, macrophage inflammatory protein 1α, and granulocyte colony-stimulating factor in BAL fluid samples obtained before HCT were higher in patients with mucopolysaccharidoses than in patients with leukodystrophies. In addition, levels of IL-1β, IL-6, IL-8, and granulocyte colony-stimulating factor were increased in the BAL fluid of patients who developed noninfectious pulmonary complications compared with those who did not develop pulmonary complications. It is interesting to note that most noninfectious pulmonary complications occurred in patients with mucopolysaccharidoses, especially diffuse alveolar hemorrhage, which occurred exclusively in patients with mucopolysaccharidoses. Higher levels of bronchial proinflammatory cytokines and chemokines may be predictive of the development of subsequent posttransplantation noninfectious complications in patients with mucopolysaccharidoses, especially those with Hurler syndrome. Larger studies will be required to further elucidate etiologic mechanisms and predictive factors.

Original languageEnglish (US)
Pages (from-to)430-437
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Bronchoalveolar lavage
  • Hematopoietic cell transplantation
  • Inflammatory cytokines
  • Inherited metabolic storage disorder
  • Pulmonary complications

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