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Journal of Clinical Oncology, Vol 21, Issue 7 (April), 2003: 1398-1403
© 2003 American Society for Clinical Oncology

PCR-Detectable Nonneoplastic Bcl-2/IgH Rearrangements Are Common in Normal Subjects and Cancer Patients at Diagnosis but Rare in Subjects Treated With Chemotherapy

Marco Ladetto, Daniela Drandi, Mara Compagno, Monica Astolfi, Federica Volpato, Claudia Voena, Anna Novarino, Berardino Pollio, Alfredo Addeo, Irene Ricca, Patrizia Falco, Federica Cavallo, Sonia Vallet, Paolo Corradini, Alessandro Pileri, Giacomo Tamponi, Antonio Palumbo, Oscar Bertetto, Mario Boccadoro, Corrado Tarella

From the Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale-Universita’ di Torino, and Divisione di Oncologia Medica-Azienda Ospedaliera San Giovanni Battista, Torino; Laboratorio di Ematologia Molecolare-Istituto Scientifico H.S. Raffaele, and Unità Trapianto Midollo Osseo, Istituto Nazionale per lo Studio e la Cura dei Tumori-Università di Milan, Italy.

Address reprint requests to Marco Ladetto, MD, Cattedra di Ematologia, Via Genova 3, 10126 Torino, Italy; email: marco.ladetto{at}unito.it.

Purpose: To assess whether nonneoplastic Bcl-2/IgH rearrangements act as a confounding factor in the setting of minimal residual disease analysis by evaluating their incidence in a panel of lymphoma-free subjects, including cancer-free donors and chemotherapy-naive and chemotherapy-treated cancer patients.

Patients and Methods: A total of 501 nonlymphoma subjects have been assessed: 258 cancer-free patients and 243 patients with malignancies other than lymphoma, 112 of whom were chemotherapy-naive. Patients were primarily assessed by nested polymerase chain reaction (PCR), followed by real-time quantitative PCR if they scored positive. In addition, six initially PCR-positive cancer-free donors were prospectively reassessed by qualitative and quantitative PCR after 30 and 60 days.

Results: The overall incidence of Bcl-2/IgH positivity was 9.6%, with a median number of 11 rearrangements per 1,000,000 diploid genomes (range, 0 to 2,845 rearrangements), as assessed by real-time PCR. The incidence was similar in healthy subjects and cancer patients at diagnosis (12% and 12.5%; P = not significant). In contrast, the incidence of this translocation was only 2.3% in chemotherapy-treated patients (P < .001). In addition, three initially PCR-positive cancer-free donors showed persistence of their rearrangements when assessed after 30 and 60 days.

Conclusion: The low incidence of nonneoplastic Bcl-2/IgH rearrangements following chemotherapy provides further evidence of the prognostic role of persistent PCR-positivity in the posttreatment molecular follow-up of follicular lymphoma patients.

Supported by Associazione Italiana Ricerca sul Cancro (AIRC), Milan, and Compagnia di San Paolo, Torino, Italy. F.V. and M.C. are recipients of a fellowship from Fondazione Angela Bossolasco. D.D. is the recipient of a fellowship from AIRC.


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