Malnutrition and Infection Drive Early Deaths in Ugandan Children with Leukaemia

In high-income hospitals, a diagnosis of acute myeloid leukaemia in a child is grim news but not usually a death sentence. Decades of dose-intensive chemotherapy, careful infection control and sophisticated supportive care have pushed five-year survival rates above seventy percent in the best paediatric oncology centres. A new study from Uganda, published in BMC Cancer, shows how starkly that picture changes when the same disease is treated with the same drugs but without the surrounding infrastructure that wealthy health systems take for granted. Among 159 children diagnosed with acute myeloid leukaemia at three Ugandan institutions between 2016 and 2022, more than one in four of those who began induction chemotherapy failed to achieve remission, and nearly twenty-eight percent of the entire cohort died early in treatment.

The research, led by Richard Nyeko of Lira University and the University of Antwerp together with colleagues at the Uganda Cancer Institute, Mulago National Specialized Hospital, Mbarara Regional Referral Hospital and partner institutions in South Africa and Belgium, set out to quantify two of the most feared events in paediatric leukaemia care: induction failure and early death. Induction failure was defined as the inability to achieve microscopic remission after the first phase of chemotherapy, including deaths that occurred during induction itself. Early death was defined more starkly as death before, or within forty-two days of, starting induction therapy. That forty-two-day window is not arbitrary; it corresponds to the standard duration of the initial intensive chemotherapy block, the period when a child’s bone marrow is deliberately wiped out by cytotoxic drugs and when the risk of overwhelming infection and bleeding is at its peak.

Acute myeloid leukaemia is a cancer of the myeloid blood-forming cells, the lineage that normally produces neutrophils, monocytes, red cells and platelets. In AML, malignant precursors crowd out normal haematopoiesis, so children frequently arrive at hospital already neutropenic, anaemic and thrombocytopenic. Induction chemotherapy, typically built around an anthracycline such as daunorubicin or idarubicin combined with cytarabine, and in many contemporary protocols with etoposide, aims to clear the blasts from the marrow. The price of that clearance is profound myelosuppression: for several weeks the child has essentially no functional immune system. In centres in high-income countries, this window is managed with laminar-flow rooms or strict isolation, broad-spectrum antibiotics delivered at the first fever, empiric antifungal therapy, ready access to irradiated blood products, and intensive nutritional support. The Ugandan data describe what happens when several of those safeguards are missing or delayed.

Of the 159 children in the cohort, 87, or 54.7 percent, were male, and the median age at diagnosis was nine years. Nearly half the children, 62 of them or 39.0 percent, were malnourished when assessed using World Health Organization growth standards, including weight-for-height, body mass index-for-age and mid-upper-arm circumference z-scores. More than a third, 59 children or 37.1 percent, presented with a peripheral white blood cell count of at least 50,000 cells per microlitre, a marker of high tumour burden that carries its own risks, including leukostasis and tumour lysis. Only 149 of the children, 93.7 percent of the cohort, actually received induction chemotherapy, meaning that some children died or deteriorated before treatment could even begin, a phenomenon almost never seen in wealthy settings.

The headline numbers are sobering. Of the 149 children who received induction chemotherapy, 39, or 26.2 percent, experienced induction failure. Early death claimed 44 of the 159 children in the cohort, a rate of 27.7 percent. The causes of those deaths read like a catalogue of the complications that intensive care is designed to prevent: sepsis accounted for 35 percent of deaths, bleeding for 25 percent, organ failure for 15 percent, severe anaemia for 13 percent, and severe pneumonia with respiratory failure for 12 percent. In other words, the majority of children who died did so not because their leukaemia was chemoresistant, but because the treatment stripped away their defences while their bodies, already weakened by malnutrition and invasive infection, could not withstand the assault.

The statistical analysis, performed with logistic regression in IBM SPSS version 27, identified consistent risk factors. Induction failure was significantly associated with malnutrition, with presumed fungal infection, and with the absence of any assessment for central nervous system involvement at diagnosis. Early death was significantly associated with malnutrition, suspected fungal infection and pneumonia. The p-values for these associations ranged from 0.031 down to 0.005, and while the retrospective design means these are associations rather than proven causal relationships, the pattern is biologically coherent. Malnutrition impairs immune competence, wound healing and drug tolerance; invasive fungal infections flourish in profoundly neutropenic patients and are difficult to diagnose without advanced imaging and galactomannan or polymerase chain reaction testing; and pneumonia in a neutropenic child can progress to fatal respiratory failure within hours.

The finding that failure to assess central nervous system involvement at diagnosis was linked to induction failure deserves particular attention. In high-income protocols, lumbar puncture with cerebrospinal fluid examination is a standard part of the AML workup, because occult leukaemic involvement of the meninges can seed relapse and requires intrathecal therapy. In resource-limited settings, this assessment may be skipped because of staffing constraints, coagulation concerns in thrombocytopenic children, or the simple pressure of competing demands on a busy ward. The Ugandan results suggest that such omissions are not benign; they mark a subset of children whose disease is being understaged and, consequently, undertreated.

What emerges from this study is not a story of clinical failure by Ugandan oncologists but a demonstration of how structural inequity is written into survival statistics. The chemotherapy regimens used, built around cytarabine and anthracyclines, are internationally recognised. The difference lies in everything that surrounds the drugs: reliable supplies of broad-spectrum antibiotics and antifungals, the laboratory capacity to identify pathogens quickly, transfusion services that can deliver platelets on demand, dietitians and nutritional rehabilitation teams, and the human resources to monitor a neutropenic child around the clock. The authors found no funding associated with the work, and the study drew on records from three public institutions that serve much of Uganda’s paediatric oncology burden, giving the findings a representative weight that single-centre reports often lack.

The implications are concrete rather than abstract. If malnutrition is independently associated with both induction failure and early death, then nutritional assessment and aggressive early feeding support should be treated as core components of leukaemia therapy in low- and middle-income settings, not as an optional extra. If suspected fungal infection and pneumonia predict both outcomes, then empiric antifungal coverage, prompt fever evaluation and lower thresholds for starting antibiotics could save lives at modest cost. If missing CNS assessment marks children destined to fail induction, then a simple lumbar puncture protocol change, with platelet support where needed, is an achievable fix. The authors emphasise the need for improved supportive care and early management of complications, and their data show exactly where that investment should be directed.

Globally, childhood cancer survival has become one of the most inequitable metrics in medicine: overall survival in high-income countries now exceeds eighty percent for many paediatric malignancies, while in much of sub-Saharan Africa the majority of children with cancer still die. AML is among the hardest cases, because its treatment is so immunologically destructive that cure depends as much on intensive care as on chemotherapy itself. This Ugandan cohort, with its 27.7 percent early death rate and its clear linkage of mortality to malnutrition and infection, quantifies that dependency with unusual clarity. The forty-two days after a child with AML begins treatment are a physiological gauntlet; in Kampala and Mbarara as much as in any city, but with far fewer nets strung beneath the tightrope. The study’s message to the global paediatric oncology community is that exporting drug protocols is not enough, and that the next great gains in childhood cancer survival in Africa will come from the unglamorous infrastructure of supportive care.

Subject of Research: Induction failure and early death in paediatric acute myeloid leukaemia in Uganda

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

Article References: Nyeko, R., Kruger, M., Niyonzima, N., Atwiine, B., Kambugu, J. B., Verhulst, S., & van Heerden, J. (2026). Induction failure and early death in paediatric acute myeloid leukaemia in Uganda: a developing country experience. BMC Cancer. https://doi.org/10.1186/s12885-026-16989-x

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16989-x

Keywords: acute myeloid leukaemia, paediatric oncology, induction failure, early death, malnutrition, fungal infection, sepsis, pneumonia, supportive care, Uganda, low- and middle-income countries, chemotherapy