title: Immune reconstitution following myeloablative allogeneic hematopoietic stem cell transplantation: the impact of expanding CD28negative CD8+ T cells on relapse.
abstract: Allogeneic stem cell transplantation has become standard therapy for hematologic malignancies through the positive immunologic graft-versus-leukemia effect. Initial immune recovery relies on peripheral expansion of infused T cells, which switch to a memory-like phenotype. This study prospectively investigated whether changes in subset composition precedes complications after myeloablative HLA-matched transplantation for hematologic malignancies. Of 80 allograft recipients, 18 were still free of clinical complication throughout 395 to 1564 days of follow-up. Compared with this complication-free subgroup, patients who developed chronic graft-versus-host disease (cGVHD) without relapsing recovered similar numbers of circulating T cells with predominance of CD8+ T cells lacking CC-chemokine receptor-7 and CD28 expression throughout the first year after transplantation. Conversely, poor CD8+ T cell recovery with diminished numbers of CD28neg CD8+ T cells (approximately 1/4th of that of relapse-free patients) preceded occurrence of malignant relapse. In multivariate analysis, lower CD28neg CD8+ T cell counts by day 60 postallograft were associated with a greater risk of subsequent relapse (hazard ratio [HR] 0.33; 95% confidence interval [CI]: 0.14-0.76; P = .01). Enumeration of CD28neg CD8+ T cells in patients could assist in predicting risk of relapse and help build an algorithm for accelerating the immune recovery by reducing the immunosuppressive treatment and considering the introduction of preemptive donor lymphocyte infusions.
authors.affiliation: Service des Maladies du Sang, UAM allogreffes de CSH, CHU, Lille, France. i-yakoub-agha@chru-lille.fr
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.forename: Pasquine
authors.initials: P
authors.lastname: Saule
authors.forename: Leonardo
authors.initials: L
authors.lastname: Magro
authors.forename: Pascale
authors.initials: P
authors.lastname: Cracco
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Bruno
authors.forename: Françoise
authors.initials: F
authors.lastname: Dufossé
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Jouet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Dessaint
authors.forename: Myriam
authors.initials: M
authors.lastname: Labalette
mesh_terms: D000293:Adolescent; D000328:Adult; D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000628:therapy; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000276:immunology; D020127:Recovery of Function / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: C515370:CCR7 protein, human; D018106:CD28 Antigens; D054400:Receptors, CCR7