title: A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol.
abstract: 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.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, University "La Sapienza" Via Benevento 6 Rome, 00161 Italy. mancini@bce.uniroma1.it
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Daniela
authors.initials: D
authors.lastname: Scappaticci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Valentina
authors.initials: V
authors.lastname: Derme
authors.forename: Loredana
authors.initials: L
authors.lastname: Elia
authors.forename: Agostino
authors.initials: A
authors.lastname: Tafuri
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Castoldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Andrea
authors.initials: A
authors.lastname: Camera
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fioritoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Fabbiano
authors.forename: Filippo
authors.initials: F
authors.lastname: Marmont
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Todeschini
authors.forename: Francesco
authors.initials: F
authors.lastname: Nobile
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Kropp
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Tabilio
authors.forename: Mario
authors.initials: M
authors.lastname: Luppi
authors.forename: Luciana
authors.initials: L
authors.lastname: Annino
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002869:Chromosome Aberrations; D002965:Classification; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015514:Oncogene Proteins, Fusion