Abstract
e18013 Background: Despite allele level HLA matching, graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). Differences in minor histocompatibility antigens impact GVHD and HCT outcome via activation of donor T cells that also mediate a graft-versus-leukemia (GVL) effect. Non-HLA determinants, such as immunomodulatory cytokines can promote or protect against GVHD. Certain cytokine gene polymorphisms have been associated with acute GVHD in related and unrelated donor HCT. Methods: 17 patients (pts) who underwent related or unrelated donor HCT for hematologic malignancies and their donors were retrospectively analyzed for polymorphisms in gene sequences for interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and interferon gamma (IFN-γ) using SSP-PCR reagents from One Lambda Inc. (Canaga Park, CA, USA). Pts and donors were categorized into low, intermediate or high producers of respective cytokines based on single nucleotide polymorphisms (SNPs) identified by sequence specific primers as per manufacturer’s instructions. Conditioning regimens included tacrolimus/sirolimus or alemtuzumab/cyclosporine. Results: A marginal association was found between development of acute GVHD and donor intermediate producers of TGF-β (p=0.056). None of the other cytokine gene polymorphisms tested showed significant relationships to either acute or chronic GVHD. Of seven pts tested who received alemtuzumab conditioning, only one pt developed GVHD; both pt and donor were high producers of all five cytokine genes tested. Conclusions: These results suggest that TGF-β gene polymorphisms may affect risk of developing acute GVHD following allogeneic HCT. Further study is warranted in larger cohorts with measurement of low, intermediate, and high cytokine producers, as well as evaluation of the interplay of cytokines and alemtuzumab in GVHD.
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