TP53 Mutations Are Associated with Increased Infections and Reduced Hematopoietic Cell Transplantation Rates in Myelodysplastic Syndrome and Acute Myeloid Leukemia

Jennifer Marvin-Peek; Emily F Mason; Ashwin Kishtagari; Reena V Jayani; Bhagirathbhai Dholaria; Tae Kon Kim; Brian G Engelhardt; Heidi Chen; Stephen Strickland; Bipin Savani; Brent Ferrell; Adetola Kassim; Michael Savona; Sanjay Mohan; Michael Byrne

doi:10.1016/j.jtct.2023.03.008

TP53 Mutations Are Associated with Increased Infections and Reduced Hematopoietic Cell Transplantation Rates in Myelodysplastic Syndrome and Acute Myeloid Leukemia

Transplant Cell Ther. 2023 Jun;29(6):390.e1-390.e10. doi: 10.1016/j.jtct.2023.03.008. Epub 2023 Mar 9.

Authors

Affiliations

¹ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
² Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
³ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
⁵ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Tennessee Oncology Midtown Center for Blood Cancers, Nashville, Tennessee. Electronic address: mbyrne@tnonc.com.

PMID: 36906277
DOI: 10.1016/j.jtct.2023.03.008

Abstract

Although allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy for patients with poor-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), only a minority of these patients undergo HCT. Patients with TP53-mutated (TP53^MUT) MDS/AML are at particularly high risk, yet fewer TP53^MUT patients undergo HCT compared with poor-risk TP53-wild type (TP53^WT) patients. We hypothesized that TP53^MUT MDS/AML patients have unique risk factors affecting the rate of HCT and thus investigated phenotypic changes that may prevent patients with TP53^MUT MDS/AML from receiving HCT. In this single-center retrospective analysis of outcomes for adults with newly diagnosed MDS or AML (n = 352), HLA typing was used as a surrogate for physician "intent to transplant." Multivariable logistic regression models were used to estimate odds ratios (ORs) for factors associated with HLA typing, HCT, and pretransplantation infections. Multivariable Cox proportional hazards models were used to create predicted survival curves for patients with and those without TP53 mutations. Overall, significantly fewer TP53^MUT patients underwent HCT compared to TP53^WT patients (19% versus 31%; P = .028). Development of infection was significantly associated with decreased odds of HCT (OR, .42; 95% CI, .19 to .90) and worse overall survival (hazard ratio, 1.46; 95% CI, 1.09 to 1.96) in multivariable analyses. TP53^MUT disease was independently associated with increased odds of developing an infection (OR, 2.18; 95% CI, 1.21 to 3.93), bacterial pneumonia (OR, 1.83; 95% CI, 1.00 to 3.33), and invasive fungal infection (OR, 2.64; 95% CI, 1.34 to 5.22) prior to HCT. Infections were the cause of death in significantly more patients with TP53^MUT disease (38% versus 19%; P = .005). With substantially more infections and decreased HCT rates in patients with TP53 mutations, this raises the possibility that phenotypic changes occurring in TP53^MUT disease may affect infection susceptibility in this population and drastically impact clinical outcomes.

Keywords: Acute myeloid leukemia; Myelodysplastic syndrome; TP53 mutation.

MeSH terms

Adult
GATA2 Deficiency*
Hematopoietic Stem Cell Transplantation*
Humans
Leukemia, Myeloid, Acute* / genetics
Leukemia, Myeloid, Acute* / therapy
Mutation / genetics
Myelodysplastic Syndromes* / genetics
Myelodysplastic Syndromes* / therapy
Retrospective Studies
Tumor Suppressor Protein p53 / genetics

Substances

TP53 protein, human
Tumor Suppressor Protein p53