Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after allogenic peripheral blood stem cell transplantation (PBSCT). Recent studies have demonstrated shortening of telomeres after chemotherapy, this shortening being equivalent to 15-40 years of ageing which has been related to genetic instability, increase risk of mutations, myelodysplastic syndromes, secondary malignancies and relapse.
To measure in vivo the effect of G-CSF administration, on the regulation of stem cells obtained from peripheral blood collected for autologous transplantation and to know its possible implications, on telomere dynamics following high-dose (HD) chemotherapy courses cyclophosphamide (CY) and HD-Ara-C for relapsed non Hodgkin's lymphoma.
Telomeric measurement was performed with real-time polymerase chain reaction (RT-PCR),in peripheral blood progenitor cells(PBPC) collected on day 5 and 10 of G-CSF administration from patients with Lymphoma, and day 0,+7,+14 and +17 post transplantation. For CD34+ cells selection, mononuclear cells were isolated from peripheral blood stem cell by Ficoll-Hypaque. The purity of CD34 selected cells was determined in a cell sorter (Becton Dickinson) using a fluorescein isothiocyanate (FICT)-conjugate monoclonal antibody (mAb).
We have shown dynamic telomere length change during the immediate reconstitution, Telomere Lenght (TL) was shorter in PBPC collected after HD-Ara-C and CY compared to TL after G-CSF administration, 6526bp vs. 4582 bp (P < 0.01). This result was confirmed on CD34+ cells. Engraftment of granulocytes and platelets come on day +13 and +19 respectively An increase in telomere length to day +19 (5962 bp) was found. Unfortunately we face with an early relapse of the same non Hodgkin's lymphoma at day +60.
Administration of G-CSF increased TL in CD34+ prevents telomere attrition after allogenic peripheral blood stem cell transplantation. The size and composition of the transplanted stem cell pool determines the ultimate telomere length. Whether PBSCT with shortened telomeres has engraftment improvement with G-CSF but risking early relapse warrants more prospective studies. We suggest that measurement of telomere length in peripheral blood collected for transplantation could be useful as a prognostic marker for engraftment/relapse in non Hodgkin's lymphoma without stem cell cryopreservation.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.