TUMOR-NECROSIS-FACTOR-ALPHA LEVELS DECREASE WITH ANTICYTOKINE THERAPYIN PATIENTS WITH MYELODYSPLASTIC SYNDROMES

Tumor necrosis factor-alpha (TNF-alpha) levels were measured in the se rum (sTNF-alpha) or bone marrow (BM) biopsies of 43 patients with myel odysplastic syndromes (MDS) who subsequently received therapy with a c ombination of pentoxifylline and ciprofloxacin (PC) with or without de xamethasone (PCD), All 43 patients received only PC therapy for 12 wee ks, after which 18 of 36 nonresponders received PCD, A total of 18 of 43 patients showed a hematologic or cytogenetic response or both. BM T NF-alpha levels were semiquantitatively assessed using inmunohistochem istry on a scale of 0-8+ and in the serum using enzyme linked immunoas say, The median TNF-alpha for the entire group was 3.0 in BM and 6.9 p g/ml in the serum, and 14 patients had no detectable levels, Responder s had higher BM levels (median 3.5 vs. 2.0) than nonresponders, althou gh this was not statistically significant. During PC therapy, a declin e in BM TNF-alpha level was seen in the entire group, which was signif icant at 2 weeks (p = 0.02), 8 weeks (p = 0.001), and 12 weeks (p = 0. 0001), Both responders (p = 0.01) and nonresponders (p = 0.03) had a d ecline at 8 weeks, but at 12 weeks, only the responders continued to s how a significant decline (p = 0.03). We conclude that MDS patients wi th high BM TNF-alpha levels have a better chance of responding to PCD therapy and that the therapy is quite successful in reducing the TNF-a lpha levels in a sustained fashion. Future studies need to be directed at identifying agents that would be more potent suppressors of the pr oapoptotic cytokines in these patients.