title: Thymic Activity and T Cell Repertoire Recovery after Autologous Hematopoietic Stem Cell Transplantation Preceded by Myeloablative Radiotherapy or Chemotherapy.
abstract: It was previously postulated that pretransplant myeloablative treatment may impair thymopoiesis, contributing in this way to delayed reconstitution of T cells after hematopoietic stem cell transplantation (HSCT). On the other hand, de novo generation of T cells after HSCT requires a competent thymus. Various myeloablative conditioning regimens (total body irradiation [TBI] or high-dose chemotherapy) routinely used in clinical practice may have potentially different impacts on the thymus. However, no comparative study on thymic output and T cell repertoire in autologous (auto)HSCT model has been presented so far. Here we evaluated thymic output and TCR diversity in 45 lymphoma patients submitted to autoHSCT differing in respect to conditioning regimen: high-dose chemotherapy as monotherapy (BEAM, n = 22) or combination of total body irradiation with cyclophosphamide chemotherapy: Cy/TBI (n = 23). Thymic output was assessed before and on days +100, +180, and +365 after autoHSCT by flow cytometric counts of recent thymic emigrant (RTE) cells (CD31(+) CD62L(+) CD45RA(+) CD4(+)) and quantification of signal joint TCR receptor excision circles (sjTRECs) by quantitative PCR. T cell repertoire diversity was analyzed on day +365 after autoHSCT by spectra-typing of the CDR3 region in the TCRVβ chain. The BEAM group, in contrast to the Cy/TBI group, manifested significantly higher proportions of RTE cells and sjTREC copy numbers on days +100 and +180. Analysis of TCRVβ spectra-types on day +365 revealed more restricted (monoclonal or oligoclonal) T cell repertoires in the Cy/TBI versus BEAM group (48.8% versus 18.2%, P = .0002). In conclusion, the conditioning scheme based on BEAM chemotherapy may be performed with lower risk of thymic destruction and T cell repertoire distortion than Cy/TBI scheme. This finding may help to potentially improve conditioning schemes to efficiently perform myeloablation and maintain active thymopoiesis.
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. Electronic address: mglowala@interia.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Głowala-Kosińska
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Chwieduk
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Smagur
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fidyk
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Najda
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Mitrus
authors.affiliation: Department of Bone Marrow Transplantation and Oncohematology, Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D064592:Autografts; D002330:Carmustine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011034:Podophyllotoxin / Q000008:administration & dosage; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine
keywords: Recent thymic emigrants (RTEs); Stem cell transplantation (autoHSCT); Thymic output; T cell receptor (TCR) repertoire; T cell reconstitution