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.