The Study of the Expression of TNF in Bone Marrow Specimens and Survival in Patients with Acute Myelogenous Leukemia.

Background: The objective of the current study was to assess the correlation between the expression of TNF from bone marrow specimens and survival in patients with acute myelogenous leukemia (AML).

Methods: Immunohistochemical analysis of bone marrow biopsies from 10 patients recently diagnosed with AML was performed using the dakocytomation LSAB + system -HRP kit, to stain for TNF binding. TNF-α and TNF-β expression were analyzed for color intensity and assigned a score from (0–5+) with 5+ being bright and over-expressed.

Results: Bone marrow specimens from 4 women and 6 men (n=10), median age 34 (range 19–61 years), all diagnosed with AML, revealed high TNF-β expression (3, 4, 5+) in 8/10 patients and high TNF-α expression (3, 4, 5+) in 6/10 patients. Median survival was 5.5 (range 1–54 months). Fisher’s exact tests for paired samples showed no correlation between predictors (age, sex, survival) and outcomes (TNF-α, TNF-β). Pearson Chi-square tests showed no correlation between predictors (age, sex, survival) and outcomes (high TNF-α / high TNF-β expression, mixed TNF-α /TNF-β expression, low TNF-α / low TNF-β expression) [See chart below]. However there was an association seen with younger males expressing both high TNF-α and high TNF-β and older women expressing low TNF-α and low TNF-β. Interestingly, the eldest patient who expressed TNF-β 4+ and TNF-α 3+ also survived the longest. He achieved clinical remission after standard induction chemotherapy, but relapsed 8 times over a course of 54 months. During each clinical remission, the patient was treated with infliximab (a TNF-α blocker) for his Crohn’s disease.

Conclusion: Level of expression of TNF-α and TNF-β of bone marrow biopsies from our AML patients showed no correlation with age, sex or overall survival given the small sample size. A large, prospective trial will be needed to determine the significance of TNF-α or TNF-β expression with survival and whether TNF-α blockade alone or in combination with chemotherapy plays a role in the treatment of patients with AML over-expressing TNF-α.