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

I. Ricca, M. Compagno, M. Ladetto, M. Rocci, M. Dell'Aquila, P. Omedè, F. De Marco, S. D'Antico, D. Caracciolo, D. Ferrero, C. Carlo-Stella, Corrado Tarella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)644-651
Number of pages8
JournalLeukemia
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2005

Keywords

  • Autograft
  • Non-Hodgkin's lymphoma
  • PBPC mobilization
  • Telomere

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

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