Severe outcomes and risk factors of non-neutropenic fever episodes in hospitalized children with cancer in Kenya

TL;DR

This study in Kenya finds that non-neutropenic fevers in children with cancer can lead to severe outcomes, highlighting the need for improved fever management in low-income settings.

Contribution

The study identifies clinical risk factors for severe outcomes in non-neutropenic fever episodes among children with cancer in a low-middle-income country.

Findings

Non-neutropenic fever episodes were associated with more severe outcomes compared to febrile neutropenia.

Acute leukemia not in remission and concern for disease relapse were significant risk factors for severe outcomes.

Blood cultures were rarely ordered during fever episodes, and most were obtained after antibiotic administration.

Abstract

Compared to febrile neutropenia (FN), non-neutropenic fever (NNF) episodes in children with cancer have not been associated with severe outcomes. Risk factors for severe outcomes in FN and NNF episodes in children with cancer from low-middle-income countries (LMIC) are incompletely described.

A prospective, observational cohort study was conducted at a tertiary public referral hospital in western Kenya. Inclusion criteria were age ≤14 years, cancer diagnosis, hospitalized, fever >38.5°C or persistently >38°C. Neutropenia was an absolute count (ANC) <500 K/µL. Severe outcomes were BSI or death. Statistical analysis detected significance between groups and a univariate analysis was conducted.

Of the 99 fevers, 54.5% were NNF episodes. Over 66% of NNF episodes were in patients with solid tumors. More severe outcomes were observed in NNF episodes compared to FN [BSI: 7.4% (4/54) vs. 4.4% (2/45); death: 7.4% (4/54) vs. 4.4% (2/45)], yet no deaths occurred in episodes with BSI. Acute leukemia not in remission (OR= 8.67, 95% CI [CI: 2.3-32.62]; p= 0.002) and concern for disease relapse (OR= 14.17, 95% CI [2.08-96.3]; p= 0.012) were significantly associated severe outcomes. Time to antibiotic administration (9 hours) did not differ by ANC. Under half (45.5%) of fever episodes had a blood culture ordered, with 93.9% obtained after administration of antibiotics.

Non-neutropenic fever episodes had more severe outcomes. Prompt fever management is recommended in all children with cancer treated in an LMIC setting. Pediatric oncology treatment centers in LMICs should rigorously evaluate their fever management clinical practice. Clinical risk factors were identified, but a risk-stratified approach in an LMIC setting is not recommended. Urgent attention is needed to identify areas of clinical improvement.

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