PMID- 37370821
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 12
DP  - 2023 Jun 16
TI  - TP53 Mutations in AML Patients Are Associated with Dismal Clinical Outcome 
      Irrespective of Frontline Induction Regimen and Allogeneic Hematopoietic Cell 
      Transplantation.
LID - 10.3390/cancers15123210 [doi]
LID - 3210
AB  - 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.
FAU - Zhao, Davidson
AU  - Zhao D
AUID- ORCID: 0000-0001-5172-6539
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON M5S 1A8, Canada.
AD  - Department of Laboratory Hematology, Laboratory Medicine Program, University 
      Health Network, Toronto, ON M5G 2C4, Canada.
FAU - Zarif, Mojgan
AU  - Zarif M
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON M5S 1A8, Canada.
AD  - Department of Laboratory Hematology, Laboratory Medicine Program, University 
      Health Network, Toronto, ON M5G 2C4, Canada.
FAU - Zhou, Qianghua
AU  - Zhou Q
AUID- ORCID: 0000-0001-7483-0478
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON M5S 1A8, Canada.
AD  - Department of Laboratory Hematology, Laboratory Medicine Program, University 
      Health Network, Toronto, ON M5G 2C4, Canada.
FAU - Capo-Chichi, Jose-Mario
AU  - Capo-Chichi JM
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON M5S 1A8, Canada.
AD  - Department of Laboratory Hematology, Laboratory Medicine Program, University 
      Health Network, Toronto, ON M5G 2C4, Canada.
FAU - Schuh, Andre
AU  - Schuh A
AD  - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON M5G 2M9, Canada.
FAU - Minden, Mark D
AU  - Minden MD
AD  - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON M5G 2M9, Canada.
FAU - Atenafu, Eshetu G
AU  - Atenafu EG
AUID- ORCID: 0000-0002-4613-3680
AD  - Department of Biostatistics, University Health Network, Toronto, ON M5G 2C4, 
      Canada.
FAU - Kumar, Rajat
AU  - Kumar R
AD  - Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 
      University Health Network, Toronto, ON M5G 2M9, Canada.
AD  - Hans Messner Allogeneic Blood and Marrow Transplantation Program, Division of 
      Medical Oncology and Hematology, Princess Margaret Cancer Centre, University 
      Health Network, Toronto, ON M5G 2M9, Canada.
FAU - Chang, Hong
AU  - Chang H
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, ON M5S 1A8, Canada.
AD  - Department of Laboratory Hematology, Laboratory Medicine Program, University 
      Health Network, Toronto, ON M5G 2C4, Canada.
LA  - eng
PT  - Journal Article
DEP - 20230616
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10296444
OTO - NOTNLM
OT  - AML
OT  - TP53
OT  - next-generation sequencing
OT  - transplantation
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/28 06:43
PMCR- 2023/06/16
CRDT- 2023/06/28 01:03
PHST- 2023/05/02 00:00 [received]
PHST- 2023/06/08 00:00 [revised]
PHST- 2023/06/12 00:00 [accepted]
PHST- 2023/06/28 06:43 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:03 [entrez]
PHST- 2023/06/16 00:00 [pmc-release]
AID - cancers15123210 [pii]
AID - cancers-15-03210 [pii]
AID - 10.3390/cancers15123210 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Jun 16;15(12):3210. doi: 10.3390/cancers15123210.