title: Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.
abstract: Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.
authors.affiliation: Laboratoire d'Immunologie Cellulaire et Tissulaire URA CNRS 625, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Malphettes
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mezard
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
authors.forename: Hester Korthals
authors.initials: HK
authors.lastname: Altes
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Brouet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D000328:Adult; D000367:Age Factors; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002469:Cell Separation; D002470:Cell Survival; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016130:Immunophenotyping; D019041:L-Selectin / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D012038:Regeneration / Q000528:radiation effects; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000502:physiology / Q000528:radiation effects*; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation
chemical_list: D018952:Antigens, CD34; D019041:L-Selectin; D017493:Leukocyte Common Antigens