Serial assessment of regulatory T cells (Tregs) in pediatric AML: A prospective study.

Abstract

9549 Background: Data of Tregs in pediatric AML is lacking. The study objectives were determining Tregs in pediatric AML at diagnosis and follow up; and correlating with outcome. Methods: From Nov 2010-May 2011, 30 consecutive AML patients ≤ 18 years were prospectively enrolled with 6 healthy controls. All patients received daunorubicin / cytarabine induction and 3 courses of cytarabine. Tregs (CD4+CD25+FoxP3+) were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow up and relapse. Results: 30 cases with median age 9.5 years; male/female ratio 14:16 had significantly higher baseline Tregs than healthy controls (12.36±4.65% vs 3.16±1.49%; p=0.0001). Patients with high Tregs frequency were females (p=0.044), WBC>50,000/mm3 (p=0.023), hypoalbuminemia (p=0.002), absence of lymphadenopathy (p=0.04) and linear correlation with peripheral blood blast% (r=0.55, p=0.0014). CR rate was 83.3% (25/30); EFS 38% and OS 73% at 14 months follow up. When Tregs were categorized as high and low based on median value, CR rate (86.6% vs 80%, p=NS), EFS [17% vs 60%, HR 1.46 (0.51-4.14) p=0.46] and OS (66% vs 80%, HR 0.58 (0.13-2.44) p=0.45) were not different. Amongst those who achieved CR, there were 7/13 relapses in those with high Tregs versus 3/12 in those with low Tregs (p=0.226).Tregs reduced post-induction (12.1±4.6 vs 6.32±2.8, p<0.000) from baseline. Using generalized estimating equation regression model, average Tregs reduction from post-induction till 3 month follow up was 0.785 units/visit (p<0.005) in those with continuous CR(n=15) and 1.25 units/visit (p<0.001) in those whom relapsed (n=10). Difference between these two groups was not significant. Tregs significantly increased at relapse as compared to post consolidation value (15.3±5.2 vs 4.5±1.9, p=0.003). Conclusions: This first study in pediatric AML demonstrates that Tregs is increased at diagnosis and is significantly associated with females, high WBC count, hypooalbuminemia, absence of lymphadenopathy and high peripheral blood blast%. Tregs significantly reduced post-induction on follow up; however, it increased at relapse. Baseline Tregs did not predict CR, EFS, or OS. However, there were more relapses in those with high baseline Tregs.