title: Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches.
abstract: Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens. However, it is currently unclear how this radically different transplantation strategy affects immunological reconstitution. To address this important issue, we used T-cell receptor Vbeta spectratype analysis to examine the distribution of complementarity-determining region 3 (CDR3)-size bands as a measure of the complexity of the redeveloping T-cell repertoire. For this study, we evaluated the T-cell repertoire of 9 patients receiving T-cell replete, matched unrelated donor transplants following fully ablative or nonmyeloablative conditioning regimens. All 4 of the myeloablative and 2 of the nonmyeloablative patients received bone marrow, whereas 3 other nonmyeloablative patients received peripheral blood stem cells. The results of the spectratype analysis demonstrated that the patients who received nonmyeloablative conditioning together with either bone marrow or peripheral blood stem cells exhibited more rapid reconstitution of T-cell repertoire complexity.
authors.affiliation: Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA. thea.friedman@mail.tju.edu
authors.forename: T M
authors.initials: TM
authors.lastname: Friedman
authors.forename: G
authors.initials: G
authors.lastname: Varadi
authors.forename: D D
authors.initials: DD
authors.lastname: Hopely
authors.forename: J
authors.initials: J
authors.lastname: Filicko
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Ferber
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: J
authors.initials: J
authors.lastname: Brunner
authors.forename: D
authors.initials: D
authors.lastname: Grosso
authors.forename: L
authors.initials: L
authors.lastname: McGuire
authors.forename: R
authors.initials: R
authors.lastname: Korngold
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D022801:Complementarity Determining Regions / Q000032:analysis; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000254:growth & development; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods* / Q000592:standards; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D018906:Antineoplastic Agents, Alkylating; D022801:Complementarity Determining Regions; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta