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

• Published in: Blood 2003-09, Vol.102 (6), p.2014-2020
• Main Authors: Cimino, Giuseppe, Elia, Loredana, Mancini, Marco, Annino, Luciana, Anaclerico, Barbara, Fazi, Paola, Vitale, Antonella, Specchia, Giorgina, Di Raimondo, Francesco, Recchia, Anna, Cuneo, Antonio, Mecucci, Cristina, Pane, Fabrizio, Saglio, Giuseppe, Foà, Robin, Mandelli, Franco
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anti-Inflammatory Agents - administration & dosage; Antibiotics, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Asparaginase - administration & dosage; Biological and medical sciences; Burkitt Lymphoma - drug therapy; Burkitt Lymphoma - genetics; Burkitt Lymphoma - mortality; Cytarabine - administration & dosage; Daunorubicin - administration & dosage; Female; Fusion Proteins, bcr-abl - genetics; Genotype; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Oncogene Proteins, Fusion - genetics; Prednisone - administration & dosage; Treatment Outcome; Vincristine - administration & dosage
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-12-3822

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 × 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.