Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation

Akiyama, Masaharu; Asai, Osamu; Kuraishi, Yasushi; Urashima, Mitsuyoshi; Hoshi, Yasutaka; Sakamaki, Hisashi; Yabe, Hiromasa; Furukawa, Tatsuo; Yamada, Osamu; Mizoguchi, Hideaki; Yamada, Hiroki

doi:10.1038/sj.bmt.1702144

Cited by 76 publications

(84 citation statements)

References 24 publications

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“…Evidence for accelerated telomere shortening after haematopoietic stem cell transplantations was found in a number of studies (Shapiro et al, 1996;Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999;Akiyama et al, 2000). Most data were derived from paediatric patients with haematological malignancies, and frequently mean TRF lengths after therapy were compared to mean TRF lengths of age-matched controls.…”

Section: Discussionmentioning

confidence: 99%

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

Schröder

Wisman²,

Jong³

et al. 2001

Br J Cancer

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High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) ( n = 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT ( n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to ( t 0 ), 5 months after ( t 1 ) and 9 months after chemotherapy ( t 2 ); these parameters were decreased at t 1 and t 2 compared to t 0 (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t 1 . Paired individual leukocyte 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 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t 0 and t 1 . Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

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

Schröder

Wisman²,

Jong³

et al. 2001

Br J Cancer

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“…In this patient population, recipients lost an average of 890 bp as a result of transplantation, which is comparable to previously published results. 24,25,27,43,44 Many investigators have noted less shortening with higher numbers of nucleated cells infused at the time of transplant 25 or in patients who receive G-CSF-mobilized peripheral blood stem cells rather than bone marrow, 45 while others report telomere loss regardless of the numbers of infused cells. 44 Several studies have shown that this accelerated telomere loss occurs within the first year post transplant with subsequent telomere loss continuing at a normal rate.…”

Section: Discussionmentioning

confidence: 99%

“…24,25,27,43,44 Many investigators have noted less shortening with higher numbers of nucleated cells infused at the time of transplant 25 or in patients who receive G-CSF-mobilized peripheral blood stem cells rather than bone marrow, 45 while others report telomere loss regardless of the numbers of infused cells. 44 Several studies have shown that this accelerated telomere loss occurs within the first year post transplant with subsequent telomere loss continuing at a normal rate. 19,25,26 Most recently, it has been suggested that telomere homeostasis, rather than shortening, may occur during the first year after transplantation in patients who receive G-CSF-mobilized peripheral blood stem cells rather than bone marrow, 45 although this was not supported in the few patients in our study who received PBSCs.…”

Section: Discussionmentioning

confidence: 99%

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients

Lewis

Mullaney

Mangan

et al. 2004

Bone Marrow Transplant

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“…Thus, T-cell senescence, as reported by other studies after BMT, 16,17 cannot be ascribed simply to the skewing of memory T cells after transplantation but also is a result of a specific reduction in the naive compartment, in accordance with their increased proliferation after treatment. Along the same lines is the observed reduction in TREC content in naive T cells with respect to normal pediatric donors as a consequence of cell proliferation and consequently TREC dilution.…”

Section: Discussionmentioning

confidence: 59%

“…[16][17][18] Because autologous stem/progenitor cells are expanded short-term ex vivo with cytokines before reinfusion, 5 GT may result in an increased senescence of the reconstituting cells.…”

mentioning

confidence: 99%

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency

Selleri

Brigida

Casiraghi

et al. 2011

Journal of Allergy and Clinical Immunology

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Background: Gene therapy (GT) with hematopoietic stem cells is a promising treatment for inherited immunodeficiencies. Objectives: Limited information is available on the relative contribution of de novo thymopoiesis and peripheral expansion to T-cell reconstitution after GT as well as on the potential effects of gene transfer on hematopoietic stem cells and lymphocyte replicative lifespan. We studied these issues in patients affected by adenosine deaminase severe combined immune deficiency after low-intensity conditioning and reinfusion of retrovirally transduced autologous CD34 1 cells. Methods: Immunophenotype, proliferative status, telomere length, and T-cell receptor excision circles were investigated at early and late time points (up to 9 years) after GT treatment. Control groups consisted of pediatric healthy donors and patients undergoing allogeneic bone marrow transplantation (BMT). Results: We observed no telomere shortening in the bone marrow compartment and in granulocytes, whereas peripheral blood naive T cells from both GT and BMT patients showed a significant reduction in telomere length compared with healthy controls. This was in agreement with the presence of a high fraction of actively cycling naive and memory T cells and lower T-cell receptor excision circles. Conclusion: These data indicate that T-cell homeostatic expansion contributes substantially to immune reconstitution, like BMT, and is not associated with senescence in the stem cell compartment. (J Allergy Clin Immunol 2011;127:1368-75.)

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Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation

Cited by 76 publications

References 24 publications

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

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

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency

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