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Haematologica. 2015 Jun;100(6):780-5. doi: 10.3324/haematol.2014.114884. Epub 2015 Feb 24.

Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial.

Author information

1
Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7 nicolas.boissel@sls.aphp.fr.
2
Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille Equipe 3 INSERM U837, JPARC Lille.
3
Service d'Hématologie, Hôpital Haut-Lévèque, Bordeaux.
4
Laboratoire Central d'Hématologie, CHU de Reims - Hôpital Robert Debré
5
Service d'Hématologie, CHU Purpan, Toulouse.
6
Service des Maladies du Sang, INSERM U892/CNRS 6299, CHU Angers.
7
Laboratoire d'Hématologie, CHU Purpan, Toulouse.
8
Service des Maladies du Sang, CHU de Lille.
9
Laboratoire d'Hématologie, CHU Angers.
10
Service d'Hématologie, Institut Paoli Calmettes, Marseille.
11
Service d'Hématologie, CHU Henri Mondor, Créteil.
12
Service d'Hématologie, CHU de Nantes.
13
Service d'Hématologie, Centre de Lutte Contre le Cancer, Rouen.
14
Service d'Hématologie, CHU Dupuytren, Limoges.
15
Service d'Hématologie Adulte, Hôpitaux de Brabois, Nancy.
16
Service d'Hématologie, CHU de Clermont Ferrand.
17
Service d'Hématologie, CHU de Reims - Hôpital Robert Debré
18
Service d'Hématologie, CHU de Poitiers.
19
Hématologie Clinique et Oncologie Médicale, CHU de Nîmes, France.
20
Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7.

Abstract

Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).

PMID:
25715404
PMCID:
PMC4450623
DOI:
10.3324/haematol.2014.114884
[Indexed for MEDLINE]
Free PMC Article

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