title: Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome.
abstract: To elucidate the biologic and clinical heterogeneity of adult pro-B acute lymphoblastic leukemia (ALL) (ie, terminal deoxynucletidyl-transferase-positive[TdT+], CD19+, CD10-, surface immunoglobulin-negative [SIg-]), we evaluated 66 patients enrolled in the Italian multicentric Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 study between October 1996 and December 1999. The ALL1/AF4 fusion transcript, originating from the t(4;11) translocation, was detected in 24 patients (36.4%), and the BCR/ABL chimeric product was found in 6 patients (9%), while the remaining 36 cases (54.6%) were ALL1/AF4-BCR/ABL-negative. A white blood cell (WBC) count higher than 50 x 109/L was found in 13 of 24, 2 of 6, and 6 of 36 of the ALL1/AF4-positive, BCR/ABL-positive, and ALL1/AF4-BCR/AB-negative patients, respectively (P =.007). None of the 24 ALL1/AF4-positive patients coexpressed the CD13 and/or CD33 myeloid antigens. By contrast, CD13 and CD33 molecules were detected, respectively, in 3 of 6 and in 14 of 33 cases of the BCR/ABL-positive patient group, and in 2 of 6 and 9 of 35 cases of the ALL1/AF4-BCR/ABL-negative patient group. These differences still remained statistically significant even if the BCR/ABL-positive patients were excluded from the analysis. A complete remission (CR) was achieved in 52 (83.4%) of the 62 patients with ALL evaluable for response to treatment. CR rates were similar in the 3 genotypic groups. By contrast, comparing patients with or without the ALL1/AF4 gene the probability of remaining in continuous complete remission (CCR) at 3.5 years was 16% and 49.8%, respectively (P =.005). Our data demonstrate that in adult pro-B-ALL a distinction should be made between pro-B-ALL cases with and without the ALL1/AF4 or the BCR/ABL chimeric genes, since the absence of both of these fusion genes correlates with a significantly better clinical outcome after intensive polychemotherapy treatment without hematopoietic stem cell transplantation.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Via Benevento 6, 00161 Rome, Italy. cimino@bce.med.uniroma1.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
authors.forename: Loredana
authors.initials: L
authors.lastname: Elia
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Luciana
authors.initials: L
authors.lastname: Annino
authors.forename: Barbara
authors.initials: B
authors.lastname: Anaclerico
authors.forename: Paola
authors.initials: P
authors.lastname: Fazi
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitale
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Anna
authors.initials: A
authors.lastname: Recchia
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Robin
authors.initials: R
authors.lastname: Foa
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011241:Prednisone / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: C403194:ALL1-AF4 fusion protein, human; D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D015514:Oncogene Proteins, Fusion; D003561:Cytarabine; D014750:Vincristine; D016044:Fusion Proteins, bcr-abl; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin