Induction failure and early death in paediatric acute myeloid leukaemia in Uganda: a developing country experience

Abstract

Abstract Introduction Dose-intensive therapy for paediatric acute myeloid leukaemia (AML) has improved outcomes in high-income countries (HICs); however, outcomes remain poor in resource-limited settings, where induction failure and early death continue to pose significant challenges. This study aimed to determine the frequency of induction failure and early death and identify associated risk factors among children treated for AML in Uganda. Methods This retrospective study examined induction failure and early death among children with AML. Data collected included demographic information, clinical characteristics, and induction outcomes for children under 18 years who were diagnosed with AML between 2016 and 2022 at three Ugandan institutions. Induction failure was defined as failure to achieve microscopic remission after induction chemotherapy, including deaths during induction. Early death was defined as death before or within 42 days of initiating induction therapy. Variables included sex, age, initial white cell count, and nutritional status, among others. Nutritional status was assessed using the World Health Organization weight-for-height, body mass index (BMI)-for-age, and mid-upper-arm circumference (MUAC) z-scores. Descriptive statistics and logistic regression analyses were performed using IBM SPSS version 27 to investigate variables associated with induction failure and early death. Results There were 159 children with AML, of whom 87 (54.7%) were males, with a median age of 9.0 years (IQR 3.0–12.0). Nearly half (n=62; 39.0%) were malnourished, and over a third (n=59; 37.1%) had a peripheral white blood cell count (WBC) at diagnosis of ≥50,000/uL. Of the 149 (93.7%) patients who received induction chemotherapy, 39 (26.2%) experienced induction failure and 27.7% early death (44/159). The main causes of death were sepsis (35%), bleeding (25%), organ failure (15%), severe anaemia (13%), and severe pneumonia with respiratory failure (12%). Induction failure was significantly associated with malnutrition (p=0.031), presumed fungal infection (p=0.043), and absence of CNS involvement assessment at diagnosis (p=0.005). Early death was associated with malnutrition (p=0.007), suspected fungal infection (p=0.008), and pneumonia (p=0.024). Conclusion In this Ugandan cohort of children with AML, induction failure and early death rates remained high and were strongly associated with infections and treatment-related complications, underscoring the challenges in AML management. Malnutrition, suspected fungal infections, and pneumonia were significantly associated with poor outcomes, highlighting the need for improved supportive care and early management of complications in resource-limited settings.