A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol
Authors
Publication date
7 April 2015
Publisher
Abstract
none32Blood. 2005 May 1;105(9):3434-41. Epub 2005 Jan 13.
A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol.
Mancini M, Scappaticci D, Cimino G, Nanni M, Derme V, Elia L, Tafuri A, Vignetti M, Vitale A, Cuneo A, Castoldi G, Saglio G, Pane F, Mecucci C, Camera A, Specchia G, Tedeschi A, Di Raimondo F, Fioritoni G, Fabbiano F, Marmont F, Ferrara F,
Cascavilla N, Todeschini G, Nobile F, Kropp MG, Leoni P, Tabilio A, Luppi M, Annino L, Mandelli F, Foà R.
Department of Cellular Biotechnologies and Hematology, University "La Sapienza" Via Benevento 6 Rome, 00161 Italy. [email protected]
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 algorith for an optimal management
of these patients.M. MANCINI; D. SCAPPATICCI; G. CIMINO; M. NANNI; V. DERME; L. ELIA; A. TAFURI; M. VIGNETTI; VITALE A; CUNEO A; CASTOLDI G; SAGLIO G; PANE F; MECUCCI C; CAMERA A; SPECCHIA G; TEDESCHI A; DI RAIMONDO F; FIORITONI G; FABBIANO F; MARMONT F; FERRARA F; CASCAVILLA N; TODESCHINI G; NOBILE F; KROPP MG; P. LEONI; TABILIO A; LUPPI M; ANNINO L; MANDELLI F; FOA RM., Mancini; D., Scappaticci; G., Cimino; M., Nanni; V., Derme; L., Elia; A., Tafuri; M., Vignetti; Vitale, A; Cuneo, A; Castoldi, G; Saglio, G; Pane, F; Mecucci, C; Camera, A; Specchia, G; Tedeschi, A; DI RAIMONDO, F; Fioritoni, G; Fabbiano, F; Marmont, F; Ferrara, F; Cascavilla, N; Todeschini, G; Nobile, F; Kropp, Mg; Leoni, Pietro; Tabilio, A; Luppi, M; Annino, L; Mandelli, F; Foa, R