Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSC T) may accelerate telomere length loss in haematopoietic stem cells. As dat a including pre-and post-treatment samples are lacking, we studied leukocyt e telomere length and telomerase activity before and after treatment in bre ast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epi rubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cy clophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemog lobin. MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these paramete rs were decreased at t(1) and t(2) compared to t(0) (high-dose: all paramet ers; standard-dose: leukocytes and platelets), and all parameters were lowe r after high-dose than standard-dose treatment at t(1). Paired individual l eukocyte samples of t(0) and t(1) showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from (+)0.8 to -2.2 k b, with a decreased TRF length in 9 patients of both groups. Telomerase act ivity (determined by TRAP assay) was below detection limit in leukocyte sam ples of t(0) and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patien ts, telomere length can be remarkably changed following haematological prol iferative stress after treatment. (C) 2001 Cancer Research Campaign.