Acute lymphoblastic leukemia (ALL) in adults has a substantial mortality within 30 days of diagnosis, defined as early mortality (EM). EM in ALL demonstrates relevant disparities between low-middle income countries (LMICs) and high-income, with reported rates of 10-25% versus <5%, respectively. This mortality gap persists due to multiple factors, exemplified by intensity of induction protocol, social disparities and others, but the precise contributors to elevated EM in LMICs remain poorly defined.

Identify independent risk factors for EM in adult ALL patients in a high-complexity cancer treatment center in São Paulo, with focus on pre-therapeutic biomarkers and treatment intensity.

Retrospective cohort study (2009–2023) including adult patients (≥ 15 years) with newly diagnosed ALL or ambiguous lineage leukemia. Pre-phase regimens varied between corticosteroid alone and corticosteroid plus cyclophosphamide. Data were analyzed using Kaplan-Meier survival estimates and competing-risk methods for 60-day outcomes. Univariate and multivariable logistic regression identified EM risk factors; variables with p < 0.2 in univariate analysis or clinical relevance were included in the multivariable model, selected by lowest Akaike Information Criterion. A two-sided p < 0.05 denoted significance.

Of 203 patients (median age 36 years; 54.2% male; 76% B-cell phenotype; 34% Philadelphia chromosome–positive), 89.8% underwent corticosteroid-only pre-phase (prednisone 49.7%, dexamethasone 16.4%, methylprednisolone 1.6%), and 32.2% received cyclophosphamide + dexamethasone. The overall EM rate was 9.8% (95%CI:6.3-15.0). In univariate analysis, low baseline serum albumin (OR 0.31; 95%CI:0.14-0.68; p = 0.004), cyclophosphamide use (OR 5.45; 95%CI:1.88-18.09; p = 0.003), positive CSF cytomorphology (OR2.82; 95%CI:0.97-7.86; p = 0.049) and year of diagnosis ≥ 2016 (protective, OR 0.24; 95%CI:0.09-0.63; p = 0.004) were associated with EM. In the best multivariable model, albumin (OR 0.27; 95%CI:0.06-0.94; p = 0.048) and cyclophosphamide pre-phase (OR8.41; 95%CI:1.42-72.28; p = 0.028). Obesity also emerged as a significant predictor (OR 7.24; 95%CI:1.07-54.72; p = 0.041). At 60 days, non-failure mortality was 11.5% (95%CI:7.5-17.0) and cumulative failure (relapse/refractory) 32%. Complete response after induction was achieved in 51.2% of patients.

Low serum albumin and cyclophosphamide use during pre-phase were strong independent predictors of EM in adult ALL patients from a Brazilian cohort. Low albumin likely reflects malnutrition and higher toxicity risk, while cyclophosphamide may worsen immunosuppression, contributing to infections - observed in 72.9% of patients. These results support the use of simple markers like albumin to guide risk-adapted pre-phase intensity. Adjusting cytoreductive therapy and antimicrobial prophylaxis could reduce EM in resource-limited settings.