Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia.
Aged
Aged, 80 and over
Chromosome Deletion
Chromosomes, Human, Pair 17
/ genetics
Clonal Evolution
/ drug effects
DNA Mutational Analysis
Decitabine
/ therapeutic use
Female
Germany
/ epidemiology
Humans
Karyotype
Karyotyping
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Monosomy
/ diagnosis
Mutation
Smith-Magenis Syndrome
/ diagnosis
Survival Analysis
Tumor Suppressor Protein p53
/ genetics
AML
Acute myeloid leukemia
Decitabine
Monosomy
Mutations
TP53
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
16
01
2020
accepted:
12
05
2020
pubmed:
7
6
2020
medline:
24
7
2020
entrez:
7
6
2020
Statut:
ppublish
Résumé
TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.
Identifiants
pubmed: 32504186
doi: 10.1007/s00277-020-04082-7
pii: 10.1007/s00277-020-04082-7
pmc: PMC7316846
doi:
Substances chimiques
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Decitabine
776B62CQ27
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1551-1560Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SPP 1463 ML 429/8-1; CRC 992 MEDEP C04; FOR 2674 LU 429/16-1
Organisme : Deutsche Forschungsgemeinschaft
ID : FOR 2674 BE 6461/1-1
Organisme : Deutsche Krebshilfe
ID : 111210
Organisme : Boehringer Ingelheim Stiftung
ID : Exploration Grant
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