Outcomes of acute Leukemia in children at the Uganda Cancer Institute
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Background: Acute leukemia is the most common cancer in children worldwide, representing approximately 25% of all childhood malignancies. Five year overall survival rates are greater than 90% and 65% to 70% for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) respectively in high income countries (HICs). In contrast, in low and middle income countries (LMICs) remission and survival rates for childhood acute leukemia are less than 35% due in part to treatment abandonment and/or lack of dedicated pediatric oncology services. In recent years, the Uganda cancer Institute has had improvement in diagnosis, treatment and follow-up of childhood acute leukemia. The outcomes of treatment and outcome predictors have not been assessed in this patient population. Objectives: This study aimed to determine the end of induction remission rates, the overall and event free survival rates and the predictors thereof in children with acute leukemia at the UCI in the setting of improved care. Methodology: We conducted a clinical retrospective cohort study among 100 children ages 0-15 years at the UCI with a diagnosis of acute leukemia. Data was abstracted from patients’ medical records into case report forms (CRFs), entered into Epi data version 3.1 before exportation into Stata version 14 (College station, TX) for analysis. To calculate the induction remission rate, the proportion of children in each subpopulation with morphological remission was obtained as a percentage of the total number of study subjects in that sub population. Kaplan-Meier survival curves and the logrank test were used to estimate and compare the overall and event-free survival of children with T-cell ALL, B-cell ALL, and AML at 5% level of significance. Multiple logistic regression was used to model the predictors of end of induction remission. Cox proportional hazard regression analysis was used to build a model of best fit that predicts overall and leukemia-free survival at 5% level of significance. Gronnesby and Borgan test were used to test the goodness of fit of this model. Results: The overall end of induction remission rate for all children with acute leukemia was 82.2% (74 of 90). Children with ALL had a remission rate of 92.2%(47 of 51), while for AML was 69.2% (27 of 39). Children with AML were 92% less likely to achieve remission than those with B-cell ALL with an adjusted odds ratio of 0.08(CI 0.01,0.76). Age at diagnosis of less than 1 year or equal or greater than 10 years made children 79% less likely to achieve remission than those with age at diagnosis of 1 to 9 years; with an adjusted odds ratio of 0.21 (CI 0.05,0.85).Overall- and event free-survival rates at 12 months were highest for children with B-cell ALL, at 89.8% (CI 71.4%, 96.7%) and 86.5% (CI 67.7%, 94.7) respectively. Children with a diagnosis of AML other than APML fared worst, with overall- and event free-survival rates at 12 months of 31% (CI 11.0%, 55.3%) and 20% ( CI 5%, 43.3%). Having AML and/or MRD ≥ 0.01% at the end of induction conferred poorer overall- and event-free survival. Conclusion and recommendations The end of induction remission rates for children with acute leukemia at the UCI are high. Survival is however significantly lower than that observed in high income countries.Children with AML and those aged less than 1 year or equal to or greater than 10 years were less likely to achieve remission at the end of induction.Children with AML were more likely to die than those with other phenotypes of acute leukemia.MRD positive status at the end of induction reduces overall and event-free survival. We recommend a prospective study to examine the reasons for a lower remission rate among children aged younger than 1 year or 10 years or older. The UCI should consider modified treatment protocols for children who are MRD positive in order to improve their survival.