CORRELATION BETWEEN TUMOR NECROSIS FACTOR-A POLYMORPHISM AND PREVALENCE OF GRAFT VS. HOST DISEASE AFTER ALLOGENEIC BONE MARROW TRANSPLANTATION.

O.Rosina, O.Gudzowaty, DS.Bernstein, and L.Isola.Department of Medicine, Division of Hematology, Tissue Typing Laboratory, Mount Sinai Medical Center, N Y.

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We analyzed the relationship between TNF-? genotypes for high and low producers and development of GvHD in 41 bone marrow transplant patients. Patients and donors were matched at HLA-A, B loci by low resolution molecular typing (equivalent to serological antigen definition), and at DRB1 locus by high resolution molecular typing (allele level).High and low producers were defined by PCR-based molecular typing for polymorphic variants (allelic substitution at position -308 in the promoter region) with cytokine genotyping trays (One Lambda Inc). TNF-? high producers were patients with genotype A/A or A/G nucleotide sequences. Gene dose effect was disregarded for this group of patients.Low producers had G/G genotype. The severity of GvHD was defined as previously described by Vogelsang, and in our cohort was independent of TNF-? genotype. 

The patients received an allogeneic unmanipulated HLA matched marrow from identical siblings or unrelated donors. Patients=age was in the range 2 to 59 (median 33). Donors=age was in the range 8 to 62 (median 35). Sex-mismatched marrow was received by 37%. The patients were treated for hematologic malignancies and aplastic anemia. GvHD prophylaxis included cyclosporin or tacrolimus, methotrexate, and prednisone (12% of the patients).

The ratio of high to low producers was 29% and 71%.GvHD was observed in 75% of TNF-? high and in 56% low producers (RR=1.6). These findings suggest that, although low producer phenotype does not exclude the development of GvHD, high producer phenotype is associated with higher incidence of GvHD.This trend is still not statistically significant (p=0.1) possibly due to the small size of the cohort.