Determinants of early mortality following induction chemotherapy in Acute Myeloid Leukemia: Experience from a comprehensive cancer center in Latin America

Abstract Background: Survival after induction chemotherapy in patients with acute myeloid leukemia (AML) is limited by both treatment-related toxicity and chemotherapy resistance. Early mortality, defined as death within the first 30 days of treatment initiation, is reported to be 3–4% in high-income countries but may reach 40% in resource-limited settings. This study aimed to: describe the demographic, epidemiological, and etiological characteristics of AML patients; identify complications and causes of death within the first 30 days of treatment; and determine pre-treatment factors associated with early mortality. Methods: We conducted a retrospective cohort study of 324 adult patients (aged ≥18 years) diagnosed with AML and treated at the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, between 2014 and 2019. Eligible patients received anthracycline-based induction chemotherapy (daunorubicin 60–90 mg/m² for 3 days) plus cytarabine (100–200 mg/m² for 5–7 days). Patients with acute promyelocytic leukemia, chronic myeloid leukemia, mixed phenotype acute leukemia, or those who received induction therapy outside INEN or were treated with hypomethylating agents or cytarabine monotherapy were excluded. Baseline clinical, pathological, and laboratory data were collected. Cytogenetic and molecular risk stratification was performed using conventional karyotyping and targeted testing for AML1-ETO, CBFB-MYH11, NPM1, and FLT3-ITD mutations. The primary outcome was early mortality, defined as death within 30 days of initiating induction therapy. Cox proportional hazards regression was used to evaluate the association between baseline characteristics and early mortality. Variables significant in univariate analysis (p < 0.05) were included in a multivariate model using backward elimination. The study was approved by the INEN Institutional Review Board. Results: The median age was 43 years; 55% were male. Most cases were de novo AML (95%). Cytogenetic/molecular risk was favorable in 23%, intermediate in 65%, and unfavorable in 12%. Early mortality occurred in 79 patients (24.3%), with a median time to death of 16 days. Frequent complications included pneumonia (80%), bacteremia (38%), and neutropenic enterocolitis (29%). ICU admission was required in 76% of cases. Septic shock was the leading cause of death (75%), followed by hemorrhage (8.9%) and respiratory failure (5.4%). On univariate analysis, age ≥45 years (HR 2.02, 95% CI 1.17–3.50, p=0.011), poor performance status (ECOG 3–4; HR 8.91, 95% CI 3.73–21.27, p<0.001), comorbidities (HR 2.30, 95% CI 1.30–4.07, p=0.004), pre-treatment infection (HR 3.64, 95% CI 2.10–6.28, p<0.001), unfavorable risk status (HR 3.46, 95% CI 1.13–10.59, p=0.029), and hypoalbuminemia (HR 0.95 per g/dL, 95% CI 0.91–0.99, p=0.017) were significantly associated with early mortality. In multivariate analysis, ECOG 3–4 (HR 8.45, p<0.001), comorbidities (HR 2.44, p=0.003), pre-treatment infection (HR 3.42, p<0.001), and unfavorable risk (HR 3.17, p=0.045) remained independently associated. Conclusion: Nearly one in four AML patients died within 30 days of induction therapy, primarily due to infection-related complications. Poor performance status, comorbidities, unfavorable risk features, and infection prior to chemotherapy were independently associated with early mortality. These findings underscore the need for early diagnosis, optimized supportive care, and timely treatment, especially in resource, limited settings.