Levels of the soluble, 55-kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence.

BACKGROUND: It has been shown that the soluble, 55-kilodalton isoform of tumor necrosis factor receptor (sTNFRp55) enhances tumor survival by exhibiting competitive ligand binding. The objective of the current study was to determine the levels of sTNFRp55 and their impact on outcome in 106 children with acute lymphoblastic leukemia (ALL) in first recurrence.

METHODS: Between January 1997 and December 2001, bone marrow (BM) samples were collected from 106 children with a first recurrence of ALL at diagnosis. These patients were enrolled in the Berlin-Frankfurt-Münster (BFM) ALL recurrence trial, ALL-REZ BFM 90-96. Levels of sTNFRp55 in BM samples were determined with a commercially available enzyme-linked immunosorbent assay kit. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate.

RESULTS: The mean sTNFRp55 level (+/- standard deviation) was 3.40 +/- 2.57 ng/mL. High levels of sTNFRp55 were associated with shorter duration of first complete remission and observation time as well as poor response to chemotherapy. Most importantly, the probability of EFS (pEFS) at 3 years was significantly worse for children with recurrent ALL who had sTNFRp55 levels greater than the median value (> 2.77 ng/mL) compared with patients who had levels that were less than the median value (pEFS: 0.44 +/- 0.10 ng/mL vs. 0.12 +/- 0.10 ng/mL; P = 0.006). It is noteworthy that the sTNFRp55 levels in 22 children with recurrent, TEL-AML1-positive ALL ([t(12;21)(p13;q22)]; 2.69 +/- 1.05 ng/mL) were significantly lower compared with the levels in children who had TEL-AML1-negative ALL (3.34 +/- 1.49 ng/mL; P < 0.05).

CONCLUSIONS: The results indicated that a high sTNFRp55 level represents a negative prognostic factor for children with recurrent ALL in terms of EFS and overall survival.