Cargando…

TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation

SIMPLE SUMMARY: TP53 mutations are adverse-risk genetic aberrations in acute myeloid leukemia (AML). The optimal treatment approach in patients with TP53-mutated (TP53(MUT)) AML remains unclear. We aimed to evaluate the prognostic implications of different frontline treatment strategies and transpla...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Davidson, Zarif, Mojgan, Zhou, Qianghua, Capo-Chichi, José-Mario, Schuh, Andre, Minden, Mark D., Atenafu, Eshetu G., Kumar, Rajat, Chang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296444/
https://www.ncbi.nlm.nih.gov/pubmed/37370821
http://dx.doi.org/10.3390/cancers15123210
_version_ 1785063660112052224
author Zhao, Davidson
Zarif, Mojgan
Zhou, Qianghua
Capo-Chichi, José-Mario
Schuh, Andre
Minden, Mark D.
Atenafu, Eshetu G.
Kumar, Rajat
Chang, Hong
author_facet Zhao, Davidson
Zarif, Mojgan
Zhou, Qianghua
Capo-Chichi, José-Mario
Schuh, Andre
Minden, Mark D.
Atenafu, Eshetu G.
Kumar, Rajat
Chang, Hong
author_sort Zhao, Davidson
collection PubMed
description SIMPLE SUMMARY: TP53 mutations are adverse-risk genetic aberrations in acute myeloid leukemia (AML). The optimal treatment approach in patients with TP53-mutated (TP53(MUT)) AML remains unclear. We aimed to evaluate the prognostic implications of different frontline treatment strategies and transplantation for patients with TP53(MUT) AML. Patients treated with intensive induction or azacitidine-venetoclax induction had no significant improvement in survival compared to patients treated with other HMA regimens despite having higher complete remission rates. Transplantation was not significantly associated with improved outcomes in time-dependent or landmark analysis, however, transplanted patients with lower TP53(MUT) variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher TP53 VAF. Current therapeutic strategies remain ineffective for TP53(MUT) AML patients, which highlights the urgent need for new treatment strategies for this high-risk population. ABSTRACT: TP53 mutations are associated with extremely poor outcomes in acute myeloid leukemia (AML). The outcomes of patients with TP53-mutated (TP53(MUT)) AML after different frontline treatment modalities are not well established. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for AML; however, long-term outcomes among patients with TP53(MUT) AML after allo-HCT are dismal, and the benefit of allo-HCT remains controversial. We sought to evaluate the outcomes of patients with TP53(MUT) AML after treatment with different frontline induction therapies and allo-HCT. A total of 113 patients with TP53(MUT) AML were retrospectively evaluated. Patients with TP53(MUT) AML who received intensive or azacitidine-venetoclax induction had higher complete remission rates compared to patients treated with other hypomethylating-agent-based induction regimens. However, OS and EFS were not significantly different among the induction regimen groups. Allo-HCT was associated with improved OS and EFS among patients with TP53(MUT) AML; however, allo-HCT was not significantly associated with improved OS or EFS in time-dependent or landmark analysis. While the outcomes of all patients were generally poor irrespective of therapeutic strategy, transplanted patients with lower TP53(MUT) variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher TP53 VAF. Our study provides further evidence that the current standards of care for AML confer limited therapeutic benefit to patients with TP53 mutations.
format Online
Article
Text
id pubmed-10296444
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102964442023-06-28 TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation Zhao, Davidson Zarif, Mojgan Zhou, Qianghua Capo-Chichi, José-Mario Schuh, Andre Minden, Mark D. Atenafu, Eshetu G. Kumar, Rajat Chang, Hong Cancers (Basel) Article SIMPLE SUMMARY: TP53 mutations are adverse-risk genetic aberrations in acute myeloid leukemia (AML). The optimal treatment approach in patients with TP53-mutated (TP53(MUT)) AML remains unclear. We aimed to evaluate the prognostic implications of different frontline treatment strategies and transplantation for patients with TP53(MUT) AML. Patients treated with intensive induction or azacitidine-venetoclax induction had no significant improvement in survival compared to patients treated with other HMA regimens despite having higher complete remission rates. Transplantation was not significantly associated with improved outcomes in time-dependent or landmark analysis, however, transplanted patients with lower TP53(MUT) variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher TP53 VAF. Current therapeutic strategies remain ineffective for TP53(MUT) AML patients, which highlights the urgent need for new treatment strategies for this high-risk population. ABSTRACT: TP53 mutations are associated with extremely poor outcomes in acute myeloid leukemia (AML). The outcomes of patients with TP53-mutated (TP53(MUT)) AML after different frontline treatment modalities are not well established. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative procedure for AML; however, long-term outcomes among patients with TP53(MUT) AML after allo-HCT are dismal, and the benefit of allo-HCT remains controversial. We sought to evaluate the outcomes of patients with TP53(MUT) AML after treatment with different frontline induction therapies and allo-HCT. A total of 113 patients with TP53(MUT) AML were retrospectively evaluated. Patients with TP53(MUT) AML who received intensive or azacitidine-venetoclax induction had higher complete remission rates compared to patients treated with other hypomethylating-agent-based induction regimens. However, OS and EFS were not significantly different among the induction regimen groups. Allo-HCT was associated with improved OS and EFS among patients with TP53(MUT) AML; however, allo-HCT was not significantly associated with improved OS or EFS in time-dependent or landmark analysis. While the outcomes of all patients were generally poor irrespective of therapeutic strategy, transplanted patients with lower TP53(MUT) variant allele frequency (VAF) at the time of diagnosis had superior outcomes compared to transplanted patients with higher TP53 VAF. Our study provides further evidence that the current standards of care for AML confer limited therapeutic benefit to patients with TP53 mutations. MDPI 2023-06-16 /pmc/articles/PMC10296444/ /pubmed/37370821 http://dx.doi.org/10.3390/cancers15123210 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Davidson
Zarif, Mojgan
Zhou, Qianghua
Capo-Chichi, José-Mario
Schuh, Andre
Minden, Mark D.
Atenafu, Eshetu G.
Kumar, Rajat
Chang, Hong
TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title_full TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title_fullStr TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title_full_unstemmed TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title_short TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell Transplantation
title_sort tp53 mutations in aml patients are associated with dismal clinical outcome irrespective of frontline induction regimen and allogeneic hematopoietic cell transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296444/
https://www.ncbi.nlm.nih.gov/pubmed/37370821
http://dx.doi.org/10.3390/cancers15123210
work_keys_str_mv AT zhaodavidson tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT zarifmojgan tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT zhouqianghua tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT capochichijosemario tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT schuhandre tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT mindenmarkd tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT atenafueshetug tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT kumarrajat tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation
AT changhong tp53mutationsinamlpatientsareassociatedwithdismalclinicaloutcomeirrespectiveoffrontlineinductionregimenandallogeneichematopoieticcelltransplantation