Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF.
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: 7226bp (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.
Ricca
I
I
Divisione di Ematologia, Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino and A. O. S. Giovanni Battista, Torino, Italy.
Compagno
M
M
Ladetto
M
M
Rocci
A
A
Dell'Aquila
M
M
Omedè
P
P
De Marco
F
F
D'Antico
S
S
Caracciolo
D
D
Ferrero
D
D
Carlo-Stella
C
C
Tarella
C
C
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018952:Antigens, CD34 / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D016615:Telomere; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects*
D000903:Antibiotics, Antineoplastic; D018952:Antigens, CD34; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone