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

Autor: Marvin-Peek J; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Mason EF; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee., Kishtagari A; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Jayani RV; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Dholaria B; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Kim TK; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee., Engelhardt BG; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Chen H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Strickland S; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Savani B; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Ferrell B; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Kassim A; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Savona M; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Mohan S; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Byrne M; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Tennessee Oncology Midtown Center for Blood Cancers, Nashville, Tennessee. Electronic address: mbyrne@tnonc.com.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2023 Jun; Vol. 29 (6), pp. 390.e1-390.e10. Date of Electronic Publication: 2023 Mar 09.
DOI: 10.1016/j.jtct.2023.03.008
Abstrakt: 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.
(Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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