A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol.
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.
Mancini
Marco
M
Department of Cellular Biotechnologies and Hematology, University "La Sapienza" Via Benevento 6 Rome, 00161 Italy. mancini@bce.uniroma1.it
Scappaticci
Daniela
D
Cimino
Giuseppe
G
Nanni
Mauro
M
Derme
Valentina
V
Elia
Loredana
L
Tafuri
Agostino
A
Vignetti
Marco
M
Vitale
Antonella
A
Cuneo
Antonio
A
Castoldi
Gianluigi
G
Saglio
Giuseppe
G
Pane
Fabrizio
F
Mecucci
Cristina
C
Camera
Andrea
A
Specchia
Giorgina
G
Tedeschi
Alessandra
A
Di Raimondo
Francesco
F
Fioritoni
Giuseppe
G
Fabbiano
Francesco
F
Marmont
Filippo
F
Ferrara
Felicetto
F
Cascavilla
Nicola
N
Todeschini
Giuseppe
G
Nobile
Francesco
F
Kropp
Maria Grazia
MG
Leoni
Pietro
P
Tabilio
Antonio
A
Luppi
Mario
M
Annino
Luciana
L
Mandelli
Franco
F
Foà
Robin
R
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
D015514:Oncogene Proteins, Fusion