Tumor necrosis factor-alpha levels decrease with anticytokine therapy in patients with myelodysplastic syndromes.
Tumor necrosis factor-alpha (TNF-alpha) levels were measured in the serum (sTNF-alpha) or bone marrow (BM) biopsies of 43 patients with myelodysplastic syndromes (MDS) who subsequently received therapy with a combination of pentoxifylline and ciprofloxacin (PC) with or without dexamethasone (PCD). All 43 patients received only PC therapy for 12 weeks, after which 18 of 36 nonresponders received PCD. A total of 18 of 43 patients showed a hematologic or cytogenetic response or both. BM TNF-alpha levels were semiquantitatively assessed using immunohistochemistry on a scale of 0-8+ and in the serum using enzyme linked immunoassay. The median TNF-alpha for the entire group was 3.0 in BM and 6.9 pg/ml in the serum, and 14 patients had no detectable levels. Responders had higher BM levels (median 3.5 vs. 2.0) than nonresponders, although this was not statistically significant. During PC therapy, a decline in BM TNF-alpha level was seen in the entire group, which was significant 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 decline at 8 weeks, but at 12 weeks, only the responders continued to show a significant decline (p = 0.03). We conclude that MDS patients with high BM TNF-alpa levels have a better chance of responding to PCD therapy and that the therapy is quite successful in reducing the TNF-alpha levels in a sustained fashion. Future studies need to be directed at identifying agents that would be more potent suppressors of the proapoptotic cytokines in these patients.
Reza
S
S
Rush Cancer Institute, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612-3515, USA.
Shetty
V
V
Dar
S
S
Qawi
H
H
Raza
A
A
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006403:Hematologic Tests; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism; D010431:Pentoxifylline / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin; D003907:Dexamethasone; D010431:Pentoxifylline