TNF Polymorphisms Independently Predict Outcome in Patients with B-Cell Non-Hodgkin’s Lymphoma

Tumour necrosis factor ل (tnfل) and lymphotoxin ل (ltل) have beenimplicated in the pathogenesis of lymphoproliferative disorders. patients with b-cellnon-hodgkin’s lymphoma (nhl) often have high serum levels of tnf which may beassociated with a poor outcome. tnfل and ltل polymorphisms are known toinfluence expression of these cytokines and may explain the variable response totherapy.patients and methods: in patients with nhl, serum levels of tnfل and ltل weremeasured. dna was typed using allele specific pcr and restriction fragment lengthpolymorphism for the –308 tnfل and +252 ltل polymorphisms and comparisonwas made with clinical outcome.results: the presence of high producing alleles was significantly associated withhigh serum levels of tnfل and ltل. the presence of 2 or more high producingalleles was significantly associated with more advanced disease at presentation(stage iii and iv), p=0.024, a higher international prognostic index (ipi) score,p=0.038, failure to achieve a complete remission (cr) after 1st line therapy (88%vs 33%, p=0.01) and shorter progression free survival (pfs) (median 24 monthscompared with 78 months, p=0.001). multivariate analysis confirmed that tnf highriskhaplotype (hrh) was an independent prognostic factor for pfs.conclusions: these results demonstrate that tnf polymorphisms are independentprognostic factors in nhl. further study is required to further define the importanceof tnf polymorphisms within different lymphoma subtypes and with differenttherapeutic approaches.