Work

Correlation of pre-hematopoietic cell transplant (HCT) pro-inflammatory cytokines in bronchioalveolar lavage (BAL) fluid with pulmonary complications following HCT in patients with inherited metabolic storage disorders (IMSDs)

Year: 2004

Type: article

Abstract: Introduction: HCT is recommended in selected patients with inherited lysosomal and peroxisomal storage disorders including the mucopolysaccharidoses (Hurler and Maroteaux-Lamy syndrome) and the leukodystrophies (adrenoleukodytsrophy [ALD], globoid cell leukodystrophy [GLD], metachromatic leukodystrophy [MLD]). However, patients with IMSDs undergoing HCT are at a higher risk of life threatening pulmonary complications such as diffuse alveolar hemorrhage (DAH) and idiopathic pneumonia syndrome (IPS). The etiology and risk factors for these complications are unknown. We obtained BAL fluid from IMSD patients prior to transplant and analyzed it for the levels of various pro-inflammatory cytokines in order to investigate their correlation with the development of subsequent pulmonary complications. Methods: Between August 1999 and March 2003, 60 BAL specimens were obtained from 48 IMSD patients pre-HCT (Hurler -21, ALD-16, MLD-6, Maroteaux-Lamy-2, GLD-1, Mucolipidosis II-1, and α-mannosidosis-1). BAL fluid was analyzed for various pro-inflammatory cytokines including IL-1β, TNF-α, IFN-γ, IL-2, IL-6, as well as chemokines including Migration Inhibitory Factor (MIP-1α) and Monocyte Chemotactic Protein (MCP). Results: In this series, the overall incidence of pulmonary complications was 54% (26/48), this included 25% (12/48) infectious complications and 29% (14/48) non-infectious complications (mainly DAH and IPS)). Evaluable pre-HCT BAL cytokine data was available on 35 patients. These included 5 patients in the infectious, 8 in the non-infectious and 22 in the no complications groups respectively. There were trends towards higher levels of pre-HCT IL-1β and IL-6 in patients who subsequently developed non-infectious complications(P = NS, however) Conclusions: Our study confirms a high incidence of pulmonary complications in the early post transplant period in patients with IMSDs. Patients with mucopolysacchridoses are at a higher risk of developing non-infectious complications like DAH as compared to patients with other IMSDs. In this study sample of 48 patients, the levels of pro-inflammatory cytokines were not found to be correlated with this increased risk; however, there were definite trends towards higher levels of IL-1β and IL-6 in the BAL fluids; this may be attributable to the small numbers of patients in the study. Further studies are needed to confirm the role of pro-inflammatory cytokines in the pathogenesis of pulmonary complications in patients with IMSDs.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2003.12.160