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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3434-3441.
Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-07-2922.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol
Marco Mancini,
Daniela Scappaticci,
Giuseppe Cimino,
Mauro Nanni,
Valentina Derme,
Loredana Elia,
Agostino Tafuri,
Marco Vignetti,
Antonella Vitale,
Antonio Cuneo,
Gianluigi Castoldi,
Giuseppe Saglio,
Fabrizio Pane,
Cristina Mecucci,
Andrea Camera,
Giorgina Specchia,
Alessandra Tedeschi,
Francesco Di Raimondo,
Giuseppe Fioritoni,
Francesco Fabbiano,
Filippo Marmont,
Felicetto Ferrara,
Nicola Cascavilla,
Giuseppe Todeschini,
Francesco Nobile,
Maria Grazia Kropp,
Pietro Leoni,
Antonio Tabilio,
Mario Luppi,
Luciana Annino,
Franco Mandelli, and
Robin Foà
From the Department of Cellular Biotechnologies and Hematology, University "La Sapienza" Rome, Italy; Dipartimento di Scienze Biomediche e Terapie Avanzate, Sezione di Ematologia, Università di Ferrara, Ferrara, Italy; Division of Hematology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; CEINGE Biotecnologie Avanzate, Department of Biochemistry and Medical Biotechnology, Federico II University, Naples, Italy; Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy; Hematology, Federico II University, Naples, Italy; Department of Hematology, University of Bari, Bari, Italy; Hematology, Niguarda Cà Granda Hospital, Milan, Italy; Department of Medical Sciences, University of Catania, Catania, Italy; Hematology, Civil Hospital, Pescara, Italy; Hematology, Hospital Cervello, Palermo, Italy; Department of Medicine, Hospital S. Giovanni Battista, Torino, Italy; Hematology, Cardarelli Hospital, Naples, Italy; Hematology, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; Department of Clinical and Experimental Medicine, University of Verona, Italy; Divisione di Ematologia Azienda Ospedaliera, Reggio Calabria, Italy; Hematology, Azienda Ospedaliera A. Pugliese, Catanzaro, Italy; Hematology, University of Ancona, Ancona, Italy; Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy; and Azienda Ospedaliera S. Giovanni Addolorata, Roma, Italy.
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.
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