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.
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.
Vey
N
N
Département of Hematology, The Institut Paoli-Calmettes, Marseille, France. veyn@marseille.fnclcc.fr
Thomas
X
X
Picard
C
C
Kovascovicz
T
T
Charin
C
C
Cayuela
J M
JM
Dombret
H
H
Dastugue
N
N
Huguet
F
F
Bastard
C
C
Stamatoulas
A
A
Giollant
M
M
Tournilhac
O
O
Macintyre
E
E
Buzyn
A
A
Bories
D
D
Kuentz
M
M
Dreyfus
F
F
Delannoy
A
A
Raynaud
S
S
Gratecos
N
N
Bordessoule
D
D
de Botton
S
S
Preudhomme
C
C
Reman
O
O
Troussard
X
X
Pigneux
A
A
Bilhou
C
C
Vernant
J P
JP
Boucheix
C
C
Gabert
J
J
D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000628:therapy*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic; D014184:Transplantation, Homologous
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D035602:Transcriptional Elongation Factors; C497422:KMT2A protein, human; C407909:TCF3 protein, human; C083400:PBX1 protein, human; C081449:AFF1 protein, human