Regulatory T cells in pediatric AML are associated with disease load and their serial assessment suggests role in leukemogenesis

Serial assessment of Treg absolute values in pediatric AML at diagnosis and follow-up; and correlating with outcome. Study design: Prospective study.

Regulatory T cells (Tregs) modulate immune system by suppressing other immune cells. In current exploratory era of immunotherapy, the detailed enumeration data of Tregs cells in pediatric AML is lacking.

This first study in pediatric AML demonstrates that Tregs are increased at diagnosis; the increased number is significantly associated with female gender and high WBC count. Tregs decrease after induction chemotherapy as compared to their baseline value. Post CR, Treg absolute values continue to decrease significantly in those who stay in CR but not so in those who relapse; this suggests their possible role in leukemogenesis.

Study objectives were determining Tregs (CD4+CD25+Foxp3+) were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse in 30 consecutive pediatric AML patients.

Patients with AML had higher baseline Treg frequencies than controls (P=0.0001). Female patients, WBC > 50,000 × 103/L and hypoalbuminemia were significantly associated with high Treg absolute values. Baseline Tregs were not associated with DFS, EFS and OS. Tregs significantly decreased after induction chemotherapy (P=0.028). Using generalized-estimating-equation regression model, Treg absolute numbers continued to decrease at each assessment time point from post-induction till 6 months follow-up (P=0.029) in those who are in continuous CR; however, in those patients who relapsed, Tregs did not change from post-induction till last follow-up preceding relapse (P=0.39). Conclusions: This first study in pediatric AML demonstrates that Tregs are increased at diagnosis; the increased number is significantly associated with female gender and high WBC count. Tregs decrease after induction chemotherapy as compared to their baseline value. Post CR, Treg absolute values continue to decrease significantly in those who stay in CR but not so in those who relapse; this suggests their possible role in leukemogenesis.