Infectious burden and cellular immune impairment in higher-risk myelodysplastic syndromes with biallelic TP53 alterations.
- 1Department of Hematology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Abstract
Higher-risk myelodysplastic syndromes (MDS) are frequently complicated by severe infections, yet the impact of molecular subgroups on infection susceptibility remains poorly defined. Biallelic TP53 (bi-TP53) alterations identify a high-risk molecular subset linked to adverse outcomes, but their contribution to infection incidence and infection-related mortality has not been systematically studied. We retrospectively analyzed 97 hospitalized higher-risk MDS patients (IPSS-R ≥4) identified through hospitalizations between June 2023 and April 2026. Patients were grouped by TP53 allelic status, and infection-related outcomes were compared. Clinically significant infections were defined as suspected or documented events requiring inpatient management and/or intravenous anti-infective therapy. Outcomes included infection incidence, recurrent infection, anti-infective escalation, baseline lymphocyte subsets, overall survival, and composite event-free survival (cEFS; infection-related death or AML transformation). Cox regression evaluated cEFS, and Firth penalized logistic regression assessed infection-related death. IPSS-M risk category was also analyzed. Among 97 patients, 31 had bi-TP53 alterations. During a median follow-up of 0.8 years, 59 patients (60.8%) developed clinically significant infections and 27 (27.8%) died from infection. Compared with non-bi-TP53 patients, bi-TP53 patients had higher rates of infection (87.1% vs. 48.5%), recurrent infection (54.8% vs. 30.3%), infection within 100 days after diagnosis (77.4% vs. 28.8%), and infection within 1 year after diagnosis (83.9% vs. 39.4%; all P<0.05). Among infected patients, bi-TP53 alterations were associated with more severe infection, greater anti-infective treatment escalation (85.2% vs. 31.3%), more frequent antifungal therapy use (74.1% vs. 15.6%), and higher infection-related mortality (85.2% vs. 12.5%; all P<0.001). Baseline neutrophil, hemoglobin, and platelet counts were comparable between groups, whereas CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and NK-cell counts were significantly lower in bi-TP53 patients. In multivariable analysis, bi-TP53 alterations remained associated with shorter cEFS (HR = 7.56, 95% CI: 2.79-20.46) and infection-related death among infected patients (OR = 7.52, 95% CI: 1.15-49.37). Bi-TP53 alterations were associated with greater infectious burden, lower circulating T-cell and NK-cell counts, and higher infection-related mortality in hospitalized patients with higher-risk MDS. These observational findings do not establish causality or independence from neutropenia. Prospective multicenter studies should assess their value for infection risk stratification and supportive-care planning.
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BibTeX
@article{lai2026infectious,
title = {{Infectious burden and cellular immune impairment in higher-risk myelodysplastic syndromes with biallelic TP53 alterations.}},
author = {Binbin Lai and Xiao Yan and Lieguang Chen and Yi Wang and Lixia Sheng and Guifang Ouyang},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1908881},
url = {https://europepmc.org/article/MED/42953204},
note = {CC BY},
}
RIS
TY - JOUR
TI - Infectious burden and cellular immune impairment in higher-risk myelodysplastic syndromes with biallelic TP53 alterations.
AU - Binbin Lai
AU - Xiao Yan
AU - Lieguang Chen
AU - Yi Wang
AU - Lixia Sheng
AU - Guifang Ouyang
PY - 2026
DA - 2026/10/14
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1908881
UR - https://europepmc.org/article/MED/42953204
AB - Higher-risk myelodysplastic syndromes (MDS) are frequently complicated by severe infections, yet the impact of molecular subgroups on infection susceptibility remains poorly defined. Biallelic TP53 (bi-TP53) alterations identify a high-risk molecular subset linked to adverse outcomes, but their contribution to infection incidence and infection-related mortality has not been systematically studied. We retrospectively analyzed 97 hospitalized higher-risk MDS patients (IPSS-R ≥4) identified through hospitalizations between June 2023 and April 2026. Patients were grouped by TP53 allelic status, and infection-related outcomes were compared. Clinically significant infections were defined as suspected or documented events requiring inpatient management and/or intravenous anti-infective therapy. Outcomes included infection incidence, recurrent infection, anti-infective escalation, baseline lymphocyte subsets, overall survival, and composite event-free survival (cEFS; infection-related death or AML transformation). Cox regression evaluated cEFS, and Firth penalized logistic regression assessed infection-related death. IPSS-M risk category was also analyzed. Among 97 patients, 31 had bi-TP53 alterations. During a median follow-up of 0.8 years, 59 patients (60.8%) developed clinically significant infections and 27 (27.8%) died from infection. Compared with non-bi-TP53 patients, bi-TP53 patients had higher rates of infection (87.1% vs. 48.5%), recurrent infection (54.8% vs. 30.3%), infection within 100 days after diagnosis (77.4% vs. 28.8%), and infection within 1 year after diagnosis (83.9% vs. 39.4%; all P<0.05). Among infected patients, bi-TP53 alterations were associated with more severe infection, greater anti-infective treatment escalation (85.2% vs. 31.3%), more frequent antifungal therapy use (74.1% vs. 15.6%), and higher infection-related mortality (85.2% vs. 12.5%; all P<0.001). Baseline neutrophil, hemoglobin, and platelet counts were comparable between groups, whereas CD3+ T-cell, CD4+ T-cell, CD8+ T-cell, and NK-cell counts were significantly lower in bi-TP53 patients. In multivariable analysis, bi-TP53 alterations remained associated with shorter cEFS (HR = 7.56, 95% CI: 2.79-20.46) and infection-related death among infected patients (OR = 7.52, 95% CI: 1.15-49.37). Bi-TP53 alterations were associated with greater infectious burden, lower circulating T-cell and NK-cell counts, and higher infection-related mortality in hospitalized patients with higher-risk MDS. These observational findings do not establish causality or independence from neutropenia. Prospective multicenter studies should assess their value for infection risk stratification and supportive-care planning.
SN - 2235-2988
ER -