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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2002-12-3822.
Submitted December 23, 2002
Accepted May 13, 2003
Clinico-biologic features and treatment outcome of adult pro-B-ALL 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
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, and Franco Mandelli
Dipartimento di Biotecnologie Celluari ed Ematologia, University 'La Sapienza', Rome, Italy
Dipartimento di Ematologia, Azienda Ospedaliera S.Giovanni Addolorata, Rome, Italy
Ematologia Policlinico, University of Bari, Bari, Italy
Cattedra di Ematologia, Ospedale Ferrarotto, Catania, Italy
Ematologia Clinica, Ospedale Civile Spirito Santo, Pescara, Italy
Hematology Unit, University of Ferrara, Ferrara, Italy
Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy
Dipartimento di Ematologia, University 'Frederico II', Naples, Italy
Dipartimernto di Scienze Biomediche ed Oncologia Umana, University of Turin, Turin, Italy
* Corresponding author; email: cimino{at}bce.med.uniroma1.it.
To elucidate the biologic and clinical heterogeneity of adult pro-B-acute lymphoblastic leukemia (ALL) (i.e. TdT+, CD19+, CD10-, SIg-), we evaluated 66 patients enrolled in the Italian multicentric 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%), 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 WBC count > 50x109/L was found in 13/24, 2/6 and in 6/36 of the ALL1/AF4-positive, BCR/ABL-positive, and ALL1/AF4-BCR/ABL-negative patients, respectively (p= .007). None of the 24 ALL1/AF4-positive patients co-expressed the CD13 and/or CD33 myeloid antigens. By contrast, CD13 and CD33 molecules were detected, respectively, in 3/6 and in 14/33, and in 2/6 and 9/35 cases of the BCR/ABL-positive and ALL1/AF4-BCR/ABL-negative patient groups. 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 ALL patients evaluable for response to treatment. CR rates were similar in the three genotypic groups. By contrast, comparing patients with or without the ALL1/AF4 gene the probability of remaining in CCR at 3.5 year 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 these fusion genes correlates with a significantly better clinical outcome after intensive polichemotherapy treatment without hemopoietic stem cell transplantation.
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