PMID- 36906277 OWN - NLM STAT- MEDLINE DCOM- 20230605 LR - 20230608 IS - 2666-6367 (Electronic) IS - 2666-6367 (Linking) VI - 29 IP - 6 DP - 2023 Jun TI - TP53 Mutations Are Associated with Increased Infections and Reduced Hematopoietic Cell Transplantation Rates in Myelodysplastic Syndrome and Acute Myeloid Leukemia. PG - 390.e1-390.e10 LID - S2666-6367(23)01166-1 [pii] LID - 10.1016/j.jtct.2023.03.008 [doi] AB - 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. CI - Copyright (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Marvin-Peek, Jennifer AU - Marvin-Peek J AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Mason, Emily F AU - Mason EF AD - Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Kishtagari, Ashwin AU - Kishtagari A AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Jayani, Reena V AU - Jayani RV AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Dholaria, Bhagirathbhai AU - Dholaria B AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Kim, Tae Kon AU - Kim TK AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Engelhardt, Brian G AU - Engelhardt BG AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Chen, Heidi AU - Chen H AD - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Strickland, Stephen AU - Strickland S AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Savani, Bipin AU - Savani B AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Ferrell, Brent AU - Ferrell B AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Kassim, Adetola AU - Kassim A AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Savona, Michael AU - Savona M AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Mohan, Sanjay AU - Mohan S AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Byrne, Michael AU - Byrne M AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Tennessee Oncology Midtown Center for Blood Cancers, Nashville, Tennessee. Electronic address: mbyrne@tnonc.com. LA - eng PT - Journal Article DEP - 20230309 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - Adult MH - Humans MH - Retrospective Studies MH - *Leukemia, Myeloid, Acute/genetics/therapy MH - *Hematopoietic Stem Cell Transplantation MH - Mutation/genetics MH - *Myelodysplastic Syndromes/genetics/therapy MH - *GATA2 Deficiency MH - Tumor Suppressor Protein p53/genetics OTO - NOTNLM OT - Acute myeloid leukemia OT - Myelodysplastic syndrome OT - TP53 mutation EDAT- 2023/03/12 06:00 MHDA- 2023/06/05 06:42 CRDT- 2023/03/11 19:32 PHST- 2023/01/12 00:00 [received] PHST- 2023/02/21 00:00 [revised] PHST- 2023/03/06 00:00 [accepted] PHST- 2023/06/05 06:42 [medline] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/11 19:32 [entrez] AID - S2666-6367(23)01166-1 [pii] AID - 10.1016/j.jtct.2023.03.008 [doi] PST - ppublish SO - Transplant Cell Ther. 2023 Jun;29(6):390.e1-390.e10. doi: 10.1016/j.jtct.2023.03.008. Epub 2023 Mar 9.