Cytoreductive treatment in patients with CALR-mutated essential thrombocythaemia: a study comparing indications and efficacy among genotypes from the Spanish Registry of Essential Thrombocythaemia.
Adolescent
Adult
Aged
Aged, 80 and over
Amino Acid Substitution
Calreticulin
/ genetics
Child
Female
Follow-Up Studies
Genotype
Humans
Hydroxyurea
/ administration & dosage
Janus Kinase 2
/ genetics
Male
Middle Aged
Mutation, Missense
Quinazolines
/ administration & dosage
Registries
Spain
Thrombocythemia, Essential
/ drug therapy
calreticulin mutation
essential thrombocythaemia
genotype
haematological response
myeloproliferative neoplasms
therapy
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
22
05
2020
accepted:
30
06
2020
pubmed:
4
8
2020
medline:
3
8
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
The present study assessed the criteria for initiating cytoreduction and response to conventional therapies in 1446 patients with essential thrombocythemia (ET), 267 (17%) of which were CALR-mutated. In low risk patients, time from diagnosis to cytoreduction was shorter in CALR-positive than in the other genotypes (2·8, 3·2, 7·4 and 12·5 years for CALR, MPL, JAK2V617F and TN, respectively, P < 0·0001). A total of 1104 (76%) patients received cytoreductive treatment with hydroxycarbamide (HC) (n = 977), anagrelide (n = 113), or others (n = 14). The estimated cumulative rates of complete haematological response (CR) at 12 months were 40 % and 67% in CALR and JAK2V617F genotypes, respectively. Median time to CR was 192 days for JAK2V617F, 343 for TN, 433 for MPL, and 705 for CALR genotypes (P < 0·0001). Duration of CR was shorter in CALR-mutated ET than in the remaining patients (P = 0·003). In CALR-positive patients, HC and anagrelide had similar efficacy in terms of response rates and duration. CALR-mutated patients developed resistance/intolerance to HC more frequently (5%, 23%, 27% and 15% for JAK2V617F, CALR, MPL and TN, respectively; P < 0·0001). In conclusion, conventional cytoreductive agents are less effective in CALR-mutated ET, highlighting the need for new treatment modalities and redefinition of haematologic targets for patients with this genotype.
Substances chimiques
CALR protein, human
0
Calreticulin
0
Quinazolines
0
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
anagrelide
K9X45X0051
Hydroxyurea
X6Q56QN5QC
Types de publication
Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
988-996Subventions
Organisme : Instituto de Salud Carlos III
ID : PI18/00205
Organisme : Instituto de Salud Carlos III
ID : PI18/00316
Organisme : European Regional Development Fund
ID : PI18/00205
Organisme : European Regional Development Fund
ID : PI18/00316
Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
Références
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