Impact of Infections in Patients with Acute Myeloid Leukemia Receiving Cytarabine+ Daunorubicin (7+3) Versus Azacitidine and Venetoclax during Induction Chemotherapy

Abstract

Introduction: Acute myeloid leukemia (AML) is a hematologic malignancy with high mortality rates due to infections, treatment-related toxicity, and multidrug-resistant (MDR) organisms, especially in resource-limited settings. Standard induction therapy includes a cytarabine‒anthracycline (7+3) regimen, cytarabine from 100 mg/m2 from Days 1-7 along with daunorubicin from 60 mg/m2 from Days 1-3 for younger, fit patients and azacitidine‒venetoclax (Aza/Ven), azacitidine administered subcutaneously at a dose of 100 mg once daily for 7 days along with  venetoclax in combination with Voriconazole during induction at a dose of 100 mg  for 21 days in elderly or younger patients with comorbidities unfit for intensive therapy. This study examined infection frequency, types, and outcomes in AML patients receiving these induction therapies at a tertiary hospital in Pakistan. Materials and Methods: This observational study included AML patients over 18 years of age treated between January 2018 and December 2023. Patients receiving the 7+3 or Aza/Ven regimen were monitored for demographics, clinical status, infection patterns, organism types, antibiotic resistance, and induction outcomes. The data were analysed with SPSS 21, and Kaplan‒Meier survival estimates, and Cox regression models were used to assess survival outcomes. Results: Among 176 AML patients, 65.3% were treated with the 7+3 regimen, whereas 34.7% received Aza/Ven. Patients receiving 7+3 regime experienced significantly greater neutropenia, which correlated with a higher infection rate and increased incidence of infections (p<0.001). Among the 106 organisms identified on blood cultures, 22(12.5%) were multidrug resistant (MDR), of which carbapenem-resistant Enterobacteriaceae (CRE) constituted 14(63%) of MDR isolates, posing a serious therapeutic challenge. The induction-related mortality rate was 31.1% in the Aza/Ven group, which was notably higher than the 21.7% reported in the 7+3 group (p-value = 0.03). The Aza/Ven regimen was linked to a sixfold increased hazard of death (p<0.001) after adjusting for age and comorbidities, underscoring a strong association between the induction regimen and patient survival. Conclusion: This study highlights the significant burden of infections and MDR organisms in AML treatment, especially in patients receiving the Aza/Ven regimen, which is commonly reserved for older and higher-risk patients. Infection prevention strategies, strict antibiotic stewardship, and tailored therapies are critical to improving outcomes. The findings advocate for continued research into optimizing induction regimens to balance efficacy and infection-related risks, particularly in resource-limited settings where AML patients face unique treatment challenges.