Journal Article

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

Buzyn, A, Bories, D, Boucheix, C, Kovascovicz, T, Picard, C, Pigneux, A, Bastard, C, Bilhou, C, Thomas, X, Dastugue, N, Preudhomme, C, Vey, N, Macintyre, E, Troussard, X, Kuentz, M, de Botton, S, Giollant, M, Cayuela, J M, Bordessoule, D, Raynaud, S, Dreyfus, F, Reman, O, Dombret, H, Delannoy, A, Gabert, J, Gratecos, N, Stamatoulas, A, Tournilhac, O, Charin, C, Vernant, J P, Huguet, F

2006

Overview

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.

• Publisher: Nature Publishing,Nature Publishing Group,Springer Nature
• Subject: Acute lymphoblastic leukemia / Adolescent / Adult / Adults / Autografts / Basic Helix-Loop-Helix Transcription Factors / Basic Helix-Loop-Helix Transcription Factors - genetics / Biological and medical sciences / Burkitt Lymphoma / Burkitt Lymphoma - genetics / Burkitt Lymphoma - therapy / Chemotherapy / Chromosome aberrations / Chromosomes, Human, Pair 1 / Chromosomes, Human, Pair 1 - genetics / Chromosomes, Human, Pair 11 / Chromosomes, Human, Pair 11 - genetics / Chromosomes, Human, Pair 19 / Chromosomes, Human, Pair 19 - genetics / Chromosomes, Human, Pair 4 / Chromosomes, Human, Pair 4 - genetics / Cytogenetics / DNA-Binding Proteins / DNA-Binding Proteins - genetics / Female / Hematologic and hematopoietic diseases / Hematology / Hematopoietic Stem Cell Transplantation / Histone-Lysine N-Methyltransferase / Humans / Immunology / Kinases / Laboratories / Leukemia / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Life Sciences / Lymphatic leukemia / Lymphocytes B / Male / Medical genetics / Medical prognosis / Medical sciences / Middle Aged / Myeloid-Lymphoid Leukemia Protein / Myeloid-Lymphoid Leukemia Protein - genetics / Nuclear Proteins / Nuclear Proteins - genetics / Pre-B-Cell Leukemia Transcription Factor 1 / Prospective Studies / Proto-Oncogene Proteins / Proto-Oncogene Proteins - genetics / Remission / Remission (Medicine) / Stem cell transplantation / Stem cells / Transcriptional Elongation Factors / Translocation, Genetic / Transplantation / Transplantation, Homologous