title: T cell reconstitution in allogeneic haematopoietic stem cell transplantation: prognostic significance of plasma interleukin-7.
abstract: Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4(+) : β = -2.1 × 10(6) cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.
authors.affiliation: Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Kielsen
authors.forename: K K
authors.initials: KK
authors.lastname: Jordan
authors.forename: H H
authors.initials: HH
authors.lastname: Uhlving
authors.forename: P L
authors.initials: PL
authors.lastname: Pontoppidan
authors.forename: Z
authors.initials: Z
authors.lastname: Shamim
authors.forename: M
authors.initials: M
authors.lastname: Ifversen
authors.forename: C
authors.initials: C
authors.lastname: Heilmann
authors.forename: C H
authors.initials: CH
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Sengeløv
authors.forename: L P
authors.initials: LP
authors.lastname: Ryder
authors.forename: K G
authors.initials: KG
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D001855:Bone Marrow Diseases / Q000628:therapy*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007223:Infant; D015851:Interleukin-7 / Q000097:blood*; D008231:Lymphopenia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7