TY - JOUR
T1 - A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL)
T2 - Analysis of the GIMEMA 0496 protocol
AU - Mancini, Marco
AU - Scappaticci, Daniela
AU - Cimino, Giuseppe
AU - Nanni, Mauro
AU - Derme, Valentina
AU - Elia, Loredana
AU - Tafuri, Agostino
AU - Vignetti, Marco
AU - Vitale, Antonella
AU - Cuneo, Antonio
AU - Castoldi, Gianluigi
AU - Saglio, Giuseppe
AU - Pane, Fabrizio
AU - Mecucci, Cristina
AU - Camera, Andrea
AU - Specchia, Giorgina
AU - Tedeschi, Alessandra
AU - Di Raimondo, Francesco
AU - Fioritoni, Giuseppe
AU - Fabbiano, Francesco
AU - Marmont, Filippo
AU - Ferrara, Felicetto
AU - Cascavilla, Nicola
AU - Todeschini, Giuseppe
AU - Nobile, Francesco
AU - Kropp, Maria Grazia
AU - Leoni, Pietro
AU - Tabilio, Antonio
AU - Luppi, Mario
AU - Annino, Luciana
AU - Mandelli, Franco
AU - Foà, Robin
PY - 2005/5/1
Y1 - 2005/5/1
N2 - The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 protocol, through the central handling of bone marrow samples at presentation, allowed us to combine cytogenetic and molecular information on a large series of adults with acute lymphoblastic leukemia (ALL) treated homogeneously, enabling us to define as broadly as possible their genetic profile and to determine the impact on outcome of the cytogenetic-molecular signature. Of 414 patients centrally processed, 325 were considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities, and hyperdiploid. The inclusion into each subgroup was based on a hierarchical approach: molecular abnormalities with adverse prognosis had precedence over karyotypic changes with less-defined prognosis and the latter over ploidy. Patients without abnormalities and those with isolated 9p/p15-p16 deletions showed a relatively favorable outcome (median disease-free survival [DFS], > 3 years). The t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1; 19)/E2A-PBX1 defined a group with dismal prognosis (median DFS, 7 months), whereas 6q deletions, miscellaneous aberrations, and hyperdiploidy predicted an intermediate prognosis (median DFS, 19 months). This study highlights the importance of a combined cytogenetic-molecular profiling of adult ALL at presentation as a critical independent determinant of their outcome, providing further evidence of the necessity of a risk-adapted therapeutic algorithm for an optimal management of these patients.
AB - The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 protocol, through the central handling of bone marrow samples at presentation, allowed us to combine cytogenetic and molecular information on a large series of adults with acute lymphoblastic leukemia (ALL) treated homogeneously, enabling us to define as broadly as possible their genetic profile and to determine the impact on outcome of the cytogenetic-molecular signature. Of 414 patients centrally processed, 325 were considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities, and hyperdiploid. The inclusion into each subgroup was based on a hierarchical approach: molecular abnormalities with adverse prognosis had precedence over karyotypic changes with less-defined prognosis and the latter over ploidy. Patients without abnormalities and those with isolated 9p/p15-p16 deletions showed a relatively favorable outcome (median disease-free survival [DFS], > 3 years). The t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1; 19)/E2A-PBX1 defined a group with dismal prognosis (median DFS, 7 months), whereas 6q deletions, miscellaneous aberrations, and hyperdiploidy predicted an intermediate prognosis (median DFS, 19 months). This study highlights the importance of a combined cytogenetic-molecular profiling of adult ALL at presentation as a critical independent determinant of their outcome, providing further evidence of the necessity of a risk-adapted therapeutic algorithm for an optimal management of these patients.
UR - http://www.scopus.com/inward/record.url?scp=20944444880&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20944444880&partnerID=8YFLogxK
U2 - 10.1182/blood-2004-07-2922
DO - 10.1182/blood-2004-07-2922
M3 - Article
C2 - 15650057
AN - SCOPUS:20944444880
VL - 105
SP - 3434
EP - 3441
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -