Serial Evaluation of T cell Subsets in Paediatric Acute Myeloid Leukaemia- a Prospective Study.

PURPOSE: There is paucity of data regarding T-cells in paediatric AML patients. The aim of this prospective study was to evaluate trend of T-cell subset during disease course of paediatric AML patients and to see its correlation with patient characteristics and survival outcome. METHODS: T-cell subsets (CD3, CD4 and CD8) were evaluated by flow-cytometry at diagnosis, post-induction, post-treatment completion, at 3 months and 6 months post-treatment completion, and relapse in 29 pediatric AML patients. Trend of T-cells was plotted between group A (those in continuous remission) and group B (those who relapsed) patients. RESULTS: Patients with high WBC count had significantly higher number of CD3, CD4 and CD8 cell. Baseline Tcell subsets did not affect CR, EFS and OS; however, higher than median CD4 count predicted improved DFS [58% vs 25%; HR = 0.306 (0.10-0.93); P = 0.037]. On serial follow-up from post-induction till 3 months after completion of therapy, there was no difference in the absolute values of T cell subsets between group A and B patients. CONCLUSION: Our study demonstrated T cell subsets are increased in AML subjects with high WBC count. CD4 cells have a positive impact on DFS. Serial follow-up has no impact on T cell subsets. Further studies in larger patient cohorts are needed to evaluate if CD4 population may serve as an immune biomarker for AML.

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

BACKGROUND: 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. AIM: Serial assessment of Treg absolute values in pediatric AML at diagnosis and follow-up; and correlating with outcome. STUDY DESIGN: Prospective study. METHODS: 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. RESULTS: 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.

Correlation of serum immunoglobulins with infection-related parameters during induction chemotherapy of pediatric acute myeloid leukemia: a prospective study.

BACKGROUND: Immune dysfunction may be a contributing factor for infections during induction chemotherapy of pediatric acute myeloid leukemia (AML); but this has not been evaluated as yet. PROCEDURE: From April 2010 to May 2011, 45 consecutive de novo pediatric AML patients were prospectively evaluated along with nine healthy controls. Immunoglobulins (Ig) (n = 45) were measured at diagnosis and day 15. RESULTS: There were 25 male and 20 female patients with a median age of 9 years (range 1-18 years). Baseline Ig did not correlate with any of the infection-related parameters during induction. At day 15, Ig levels reduced from baseline (IgG p = 0.46, IgA p = 0.027, IgM p < 0.001). Day 15 IgG levels were lower in patients with persistent fever >7 days (p = 0.029) and fungal infection (p = 0.035). CONCLUSION: This is the first study which has evaluated derangement in Ig with infection-related parameters in pediatric AML. At day 15, immunoglobulins decrease and reduced IgG levels correlate with infection-related parameters. Use of intravenous immunoglobulins in pediatric AML cases needs to be further evaluated to assess whether it can reduce infection-related morbidity.

Baseline low immunoglobulin A predicts inferior disease-free survival in pediatric acute myeloid leukemia and serial evaluation suggests role of immunoglobulin A in leukemogenesis.

Abstract Data on serial evaluation of immunoglobulins (Ig) in pediatric AML is lacking. From April 2010 to May 2011, 45 consecutive patients with AML aged 1-18 years were prospectively enrolled along with nine healthy controls. Ig were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse. At diagnosis, Ig levels were significantly higher in patients than in healthy controls. Patienths with gum hypertrophy had low Ig levels (IgG, p = 0.007; IgA, p = 0.003; IgM, p = 0.06). Baseline Ig did not correlate with complete remission (CR). Patients who relapsed had a lower baseline IgA level than those in continuous CR (169 ± 94 g/dL vs. 310 ± 177 g/dL, p = 0.019). Patients with a low baseline IgA level (less than median) had inferior disease-free-survival (DFS) on multivariate analysis (p = 0.048). Post-induction, IgM (p < 0.001) and IgA (p = 0.048) were significantly reduced as compared to their baseline values. On serial follow-up in patients who were in continuous CR, there was a significant decrease in IgA from post-induction until 6 months after treatment completion. This is the first study to evaluate the trend of humoral immunity in sequential pediatric patients with AML. Our study demonstrates that in pediatric AML, baseline Ig were higher than in controls. Gum hypertrophy was observed in patients with low Ig (IgA and IgG) levels. Relatively lower baseline IgA predicted disease relapse and inferior DFS. On serial follow-up, IgA significantly decreased in those who continued to stay in CR but not in patients who relapsed, suggesting an association of IgA with leukemogenesis.