The Significance of soluble CD40 and CD40 ligand levels in childhood acute lymphoblastic leukemia patients

Abstract

Background and aim: Acute lymphoblastic leukemia (ALL) is the most prevalent malignant disorder in childhood. CD40 is a member of the tumor necrosis factor (TNF) receptor family. Soluble CD40 (sCD40) was previously found to be associated with poor prognosis in adult patients with hematologic malignancies such as acute myeloid leukemia (AML) and multiple myeloma. Experience in children, however, is rather limited. The present study aimed to investigate the significance of sCD40 and sCD40 ligand in children with ALL. Materials and Method: This study recruited 44 children treated at Erciyes University, Division of Pediatric Hematology & Oncology between February 2008 and February 2010. We investigated the relationship between sCD40/sCD40 ligand at the diagnosis and remission during continuation phase with the prognosis of children with ALL. We also considered the data on treatment response, relapse, and outcome. Findings: The participating patients (20 girls and 25 boys) were between 22 months - 18 years (mean 7.6 ± 4.6 years) and had leukocytes at diagnosis between 870 - 741,660/mm3 (median 15,150/mm3). Thirty-five patients were diagnosed with B, whereas nine were diagnosed with T phenotype. In this cohort, 13 patients were classified in the standard-risk (SR) group, 20 patients were put in the intermediate-risk (IR) group, and 11 patients were categorized in the (HR) group according to the Turkish Acute Lymphoblastic Leukemia Berlin Frankfurt Munich (TR-ALL BFM) protocol. The serum levels of CD40/CD40 ligand at diagnosis were 22.41±9.91 ng/ml and 15.17±5.49 ng/ml, respectively, whereas these levels at remission were 0.22±0.38 ng/ml and 1.04±0.51 ng/ml, respectively. We detected significant changes in CD40 and CD40 ligand levels (p = 0.008 and p<0.005, respectively) and early response on the 8th day. Although not significantly correlated with sCD40, the final outcome had a significant relationship with early response detected on the 8th day of treatment. We found the cut-off value of sCD40 to be 28.15 ng/dL in our cohort. The effect of sCD40 on event-free survival was clinically significant, but it did not yield statistical significance. Conclusion: Overall, our findings suggest that sCD40 is measured as increased at diagnosis of childhood ALL. On the basis of its physiological effect, sCD40 may have a role in modulating antitumor response in pediatric ALL and be a useful prognostic marker.