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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2002-12-3639.
Submitted December 3, 2002
Accepted March 26, 2003
Chronic lymphocytic leukemia patients with highly stable and indolent disease show distinctive phenotypic and genotypic features
Anna Guarini, Gianluca Gaidano, Francesca Romana Mauro, Daniela Capello, Francesca Mancini, Maria Stefania De Propris, Marco Mancini, Enrica Orsini, Massimo Gentile, Massimo Breccia, Antonio Cuneo, Gianluigi Castoldi, and Robert Foa*
Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita 'La Sapienza', Rome, Italy
Dipartimento di Scienze Mediche & IRCAD, Universita del Piemonte Orientale, Novara, Italy
Dipartimento di Scienze Biomediche e Terapie Avanzate, Universita degli Studi, Ferrara, Italy
* Corresponding author; email: rfoa{at}bce.uniroma1.it.
Different biologic features have been associated with a more or less aggressive clinical course in chronic lymphocytic leukemia (CLL). In the present study, 20 patients with highly stable CLL observed at a single institution over a period of 10-23 years and who never required treatment have been extensively characterized. The aim was to identify a distinct and reproducible biologic profile associated with disease stability that may be utilized to recognize at presentation CLL patients who are likely to have a very benign clinical course and for whom treatment is not indicated. The results obtained indicate that numerous parameters are closely associated with disease stability: a typical CLL morphology and immunophenotype, the lack of expression of the CD38 antigen, the mutated IgVH pattern, the absence of p53 mutations, a CD4/CD8 ratio >1, the lack of 17p and 11q deletions, as well as of complex karyotypic aberrations, and the occurrence of the 13q14 deletion. No case displayed the VH3-21 gene that has been linked in mutated CLL with a poor outcome. In addition, the VH1-69 gene associated with unmutated CLL cases was never detected. These biologic features were coupled with an indolent clinical course characterized by an unmodified clinical stage from diagnosis to the time of this study, lack of autoimmune phenomena and of major infections requiring parental antibiotics. At a time when aggressive therapeutic strategies are always more frequently being utilized in the management of CLL, the distinctive features of patients with long- lived stable disease should be prospectically identified at presentation.
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