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Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study

Authors :
Vey, N.
Thomas, X.
Picard, C.
Kovascovicz, T.
Charin, C.
Cayuela, J. M.
Dombret, H.
Dastugue, N.
Huguet, F.
Bastard, C.
Stamatoulas, A.
Giollant, M.
Tournilhac, O.
Macintyre, E.
Buzyn, A.
Bories, D.
Kuentz, M.
Dreyfus, F.
Delannoy, A.
Raynaud, S.
Gratecos, N.
Bordessoule, Dominique
De Botton, S.
Preudhomme, C.
Reman, O.
Troussard, X.
Pigneux, A.
Bilhou, C.
Vernant, J. P.
Boucheix, C.
Gabert, J.
Renseigné, Non
Laboratoire de chimie et biochimie des substances naturelles
Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN)
Danone Research
Groupe DANONE
Recherche & Développement
EDF (EDF)
Service greffe de moelle osseuse
Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Laboratoire d'oncohématologie
Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice)
Service d'Hématologie biologique [CHU Limoges]
CHU Limoges
Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges]
Université de Limoges (UNILIM)
Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL)
Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)
Laboratoire d'Hématologie
Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Différenciation hématopoïétique normale et leucémique
Institut National de la Santé et de la Recherche Médicale (INSERM)
Institut de biologie et chimie des protéines [Lyon] (IBCP)
Université Claude Bernard Lyon 1 (UCBL)
Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Source :
Leukemia, Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2006, 20 (12), pp.2155-61. ⟨10.1038/sj.leu.2404420⟩
Publication Year :
2006
Publisher :
HAL CCSD, 2006.

Abstract

International audience; Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.

Subjects

Subjects :
Male
Oncology
Cancer Research
MESH: Chromosomes, Human, Pair 19
medicine.medical_treatment
Translocation, Genetic
0302 clinical medicine
hemic and lymphatic diseases
MESH: Basic Helix-Loop-Helix Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
Prospective Studies
E2a pbx1
Prospective cohort study
Acute leukemia
MESH: Middle Aged
Pre-B-Cell Leukemia Transcription Factor 1
Hematopoietic Stem Cell Transplantation
Nuclear Proteins
hemic and immune systems
Hematology
Middle Aged
Burkitt Lymphoma
MESH: Translocation, Genetic
3. Good health
DNA-Binding Proteins
Chromosomes, Human, Pair 1
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Chromosomes, Human, Pair 4
Transcriptional Elongation Factors
Stem cell
Myeloid-Lymphoid Leukemia Protein
Adult
medicine.medical_specialty
MESH: Chromosomes, Human, Pair 4
Adolescent
MESH: Chromosomes, Human, Pair 1
03 medical and health sciences
Proto-Oncogene Proteins
Internal medicine
Acute lymphocytic leukemia
medicine
MESH: Transplantation, Homologous
Humans
Transplantation, Homologous
neoplasms
MESH: Hematopoietic Stem Cell Transplantation
MESH: Adolescent
Chemotherapy
MESH: Humans
business.industry
Chromosomes, Human, Pair 11
MESH: Adult
Histone-Lysine N-Methyltransferase
B-cell acute lymphoblastic leukemia
medicine.disease
MESH: Male
MESH: Prospective Studies
Surgery
Transplantation
MESH: Burkitt Lymphoma
MESH: Proto-Oncogene Proteins
MESH: Myeloid-Lymphoid Leukemia Protein
MESH: Chromosomes, Human, Pair 11
business
Chromosomes, Human, Pair 19
MESH: Female
MESH: Nuclear Proteins
MESH: DNA-Binding Proteins
030215 immunology

Details

Language :
English
ISSN :
08876924 and 14765551
Database :
OpenAIRE
Journal :
Leukemia, Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2006, 20 (12), pp.2155-61. ⟨10.1038/sj.leu.2404420⟩
Accession number :
edsair.doi.dedup.....90ea607d2928a1389b689b9337747a51
Full Text :
https://doi.org/10.1038/sj.leu.2404420⟩