#8: Survival Analysis in Childhood Acute Myeloblastic Leukemia: Do Infection and Lymphocyte-Mediated Immune Response Play a Role?

Abstract

Background Acute myeloblastic leukemia (AML) is the second most prevalent cancer among Indonesian children. In contrast, to those of acute lymphoblastic leukemia (ALL), a number of studies reported unfavorable outcomes following the initiation of cytostatic protocols for childhood AML. In addition, our previous study showed that Gram-negative bacterial infection constitutes the major cause of treatment-related mortality in children with AML. These findings raised a question on the prognostic role of diagnostic lymphopenia, which represents the immunosuppressive state, as demonstrated in adult patients with solid tumors. Methods A retrospective cohort study, which involved children younger than 18 years of age with the newly diagnosed, non-M3 AML, was conducted. These children were admitted to Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the period of 2011–2019 and received National Pilot Protocol (2011–2016), Pediatric AML Protocol (2016–2018), and International Society of Pediatric Oncology (SIOP) Pediatric Oncology in Developing Countries (PODC) Protocol with prephase (2018–2019). One-year overall survival (OS) was analyzed, using diagnostic absolute lymphocyte counts (ALC0) of more than 4.5 × 109/L and less than 4.5 × 109/L as the determinants, in accordance with those reported in a number of studies on adult AML. Results Sixty-five children, which consisted of 41 (63%) children with ALC0 of more than 4.5 × 109/L and 24 (37%) children with ALC0 of less than 4.5 × 109/L, were eligible for this study. Of these 65 children, 56 (86%) children received Cytosine arabinoside in the first week of treatment (National Pilot Protocol and Pediatric AML Protocol), while 9 (14%) children did not (SIOP PODC Protocol with prephase). OS analysis showed that 44% and 19% of children with ALC0 of more than 4.5 × 109/L and ALC0 of less than 4.5×109/L, respectively, were alive within the first year of treatment. Cox-regression analysis, however, failed to reach statistical significance [hazard ratio (HR), 0.63; 95% confidence interval (95% CI), 0.33–1.18; P = 0.15]. Conclusion Despite lacked statistical significance, our study showed the superior one-year OS in children with ALC0 of more than 4.5 × 109/L. Our findings, therefore, might indicate the prognostic role of infection and lymphocyte-mediated immune response in childhood AML.