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Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

ABSTRACT: Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.

SUBMITTER: Schnetzke U

PROVIDER: S-EPMC11327101 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

Schnetzke Ulf U Fischer Mike M Röllig Christoph C Scherag André A Altmann Heidi H Stölzel Friedrich F Alakel Nael N Bornhäuser Martin M Hochhaus Andreas A Scholl Sebastian S

Genes and immunity 20240709 4

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, ...[more]

PMID: 38982248

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Project description:BackgroundThe majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes in patients with acute myeloid leukemia (AML).Methods16s rRNA-based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion.ResultsAt the start of IC, higher stool Shannon diversity (hazard ratio [HR], 0.36; 95% confidence interval [CI], .18-.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, .18-.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum β-lactamase-producing organism. Patients who received carbapenems for >72 hours had significantly lower α-diversity at neutrophil recovery (P = .001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73-11.93).ConclusionsOur results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications in AML patients.Baseline microbiome diversity is a strong independent predictor of infection during acute myeloid leukemia induction chemotherapy (IC) among clinical and microbiome covariates. Higher baseline levels of Porphyromonadaceae appear protective against infection, while carbapenem use is associated with consequences to the microbiome and infection susceptibility post-IC.

Dataset Information

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

Publications

Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

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