Document Detail


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.
MedLine Citation:
PMID:  12791662     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Giuseppe Cimino; Loredana Elia; Marco Mancini; Luciana Annino; Barbara Anaclerico; Paola Fazi; Antonella Vitale; Giorgina Specchia; Francesco Di Raimondo; Anna Recchia; Antonio Cuneo; Cristina Mecucci; Fabrizio Pane; Giuseppe Saglio; Robin Foa; Franco Mandelli;
Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2003-06-05
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-08     Completed Date:  2003-10-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2014-20     Citation Subset:  AIM; IM    
Affiliation:
Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Via Benevento 6, 00161 Rome, Italy. cimino@bce.med.uniroma1.it
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MeSH Terms
Descriptor/Qualifier:
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
Burkitt Lymphoma / drug therapy*,  genetics*,  mortality
Cytarabine / administration & dosage
Daunorubicin / administration & dosage
Female
Fusion Proteins, bcr-abl / genetics*
Genotype
Humans
Male
Middle Aged
Oncogene Proteins, Fusion / genetics*
Prednisone / administration & dosage
Treatment Outcome
Vincristine / administration & dosage
Chemical
Reg. No./Substance:
0/ALL1-AF4 fusion protein, human; 0/Anti-Inflammatory Agents; 0/Antibiotics, Antineoplastic; 0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents, Phytogenic; 0/Fusion Proteins, bcr-abl; 0/Oncogene Proteins, Fusion; 147-94-4/Cytarabine; 20830-81-3/Daunorubicin; 53-03-2/Prednisone; 57-22-7/Vincristine; EC 3.5.1.1/Asparaginase

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