TP53 mutations are associated with increased rates of infections and a reduced rate of hematopoietic cell transplantation (HCT) in myelodysplastic syndrome and acute
myeloid leukemia (MDS/AML), according to research published in Transplant and Cellular Therapy.
Researchers conducted a single center retrospective analysis of outcomes for adults with newly diagnosed MDS/AML to investigate whether patients with TP53-mutated disease have unique risk factors affecting rates of HCT relative to those with TP53-wildtype disease.
The team used multivariable models to estimate odds ratios (OR) for factors associated with HLA typing (as a surrogate for physician “intent to transplant”), HCT, and pretransplant infections and to create predicted survival curves for patients with and without TP53 mutations.
A total of 352 patients were included in the study. Of those, 91 patients (25.9%) had TP53-mutated disease. Patients with mutated TP53 were older (mean, 66.4 vs 61.9 years; P =.013) and had worse ECOG performance status at diagnosis (ECOG PS ≥1, 34% vs 20%; P< .001) than patients with wildtype TP53. The median follow-up duration was 14.4 months (interquartile range [IQR], 4.4-35.8).
HLA typing indicated 51.4% of patients had physician intent to proceed with allogeneic HCT (50% in TP53 mutated vs 52% in TP53 wild type; P =.85). At a median time of 6.2 months following diagnosis (IQR, 5.0-9.5), 28% of patients underwent HCT. Significantly fewer patients with TP53 mutated disease underwent HCT compared to patients with TP53-wildtype disease (19% vs 31%; P =.028).
The researchers found that pre-transplant infection was associated with decreased odds of HCT (OR, 0.42; 95% CI, 0.19-0.90) and worse overall survival (hazard ratio [HR], 1.46; 95% CI, 1.09-1.96) in multivariable analyses. They also found TP53-mutated disease was independently associated with increased odds of pre-transplant infection (OR, 2.18; 95% CI, 1.21-3.93), bacterial pneumonia (OR, 1.83; 95% CI, 1.00-3.33), and invasive fungal infection (OR, 2.64; 95% CI, 1.34-5.22) and significantly more patients with TP53-mutated than those with TP53-wildtype disease died of infection (38% vs 19%; P =.005).
“We found that mutations in TP53 were associated with a substantially increased risk of infection even when controlling for age, lines of treatment, and degree of neutropenia in patients with MDS or AML,” the authors wrote in their report. “These results highlight how phenotypic differences in [TP53-mutated] myeloid neoplasms may impact clinical outcomes and how better understanding the disease biology of these patients could be of therapeutic benefit.”
Limitations of the study included the retrospective design, limited sample size, and inability to assess for copy-neutral loss of heterozygosity.
Marvin-Peek J, Mason EF, Kishtagari A, et al. TP53 mutations are associated with increased infections and reduced hematopoietic cell transplantation rates in myelodysplastic syndrome and acute myeloid leukemia. Transplant Cell Ther. Published online March 9, 2023. doi:10.1016/j.jtct.2023.03.008