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Lymphoma

Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF

Leukemia volume 19, pages 644–651 (2005)Cite this article

Abstract

The purpose of the study was to compare telomere length (TL) in peripheral blood progenitor cells (PBPC) collected after two tightly spaced high-dose (hd) chemotherapy courses. We assessed 37 previously untreated lymphoma patients undergoing a hd-chemotherapy program with autografting. They sequentially received hd-cyclophosphamide (CY) and hd-Ara-C, both followed by PBPC harvesting. Both post-CY and post-Ara-C harvests were assessed for TL by Southern blot analysis. In 12 patients, the assay was also performed on purified CD34+ cells. All patients displayed high PBPC mobilization following both hd-CY and hd-Ara-C. In all but one patient, TL was shorter in PBPC collected after Ara-C compared to CY: 7226 bp (range: 4135–9852) vs 8282 bp (range 4895–14860) (P<0.0001). This result was confirmed on CD34+ cells. Platelet recovery in patients receiving post-Ara-C PBPC was significantly slower compared to those receiving post-CY PBPC. In conclusion, (i) administration of tightly spaced hd-chemotherapy courses induces marked telomere shortening on harvested PBPC; (ii) engraftment kinetics seem slower, with delayed platelet recovery, in patients autografted with PBPC suffering marked TL erosion; (iii) long-term follow-up is required to verify whether PBPC with shortened telomeres display defective engraftment stability and/or risk of secondary leukemia; (iv) TL evaluation is advisable whenever new mobilization procedures are developed.

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Acknowledgements

This work was supported in part by grants from Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR), Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.), Ricerca Finalizzata Regione Piemonte and Ministero della Salute and the Michelangelo Foundation for Advances in Cancer Research and Treatment. IR is recipient of a fellowship from Fondazione Italiana Ricerca sul Cancro (FIRC), Milan, Italy. MC and MDA have been supported by a fellowship from A Bossolasco (MC) and from G Ghirotti (MDA) Foundations, Turin, Italy.

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  1. Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Universita' di Torino and A. O. S. Giovanni Battista, Torino, Italy

    I Ricca, M Compagno, M Ladetto, A Rocci, M Dell'Aquila, P Omedè, F De Marco, D Caracciolo, D Ferrero & C Tarella

  2. Banca del Sangue di Torino – A. O. S. Giovanni Battista, Torino, Italy

    S D'Antico

  3. Medical Oncology Unit, Istituto Nazionale Tumori, University of Milano, Milano, Italy

    C Carlo-Stella

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Ricca, I., Compagno, M., Ladetto, M. et al. Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF. Leukemia 19, 644–651 (2005). https://doi.org/10.1038/sj.leu.2403652

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