title: Complete donor T cell chimerism predicts lower relapse incidence after standard double umbilical cord blood reduced-intensity conditioning regimen allogeneic transplantation in adults.
abstract: Double umbilical cord blood (dUCB) allogeneic transplantation after a low-dose total body irradiation, cyclophosphamide, and fludarabine (TCF)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there are little data regarding the long-term outcome of CD3(+) T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases who received dUCB allogeneic transplants conditioned with TCF were included in this retrospective study. Peripheral blood CD3(+) TCC was considered until day +100 after transplantation to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3(+) TCC, respectively, within the first 100 days after transplantation. With a median follow-up of 36 months, 3 year-overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were 61%, (95% confidence interval [CI], 43% to 75%); 50% (95% CI, 32.5% to 66%), and 28% (95% CI, 16% to 44%), respectively. In univariate analysis, a full CD3(+) TCC was associated with a better 3-year DFS: 59% (95% CI, 39% to 75.5%) versus 14% (95% CI, 7% to 46%); hazard ratio (HR), .24 (.09 to .65); P = .005 and a lower CIR: 24% (95% CI, 21.5% to 57%) versus 78% (95% CI, 52% to 99%); HR, .18 (.05 to .50); P = .004. In multivariate analysis, a full CD3(+) TCC remained associated with a lower CIR (HR, .17 [.028 to .99]; P = .049). CD3(+) TCC has no impact on graft-versus-host disease and nonrelapse mortality in this study. In conclusion, here, full CD3(+) TCC was independently associated with a lower risk of relapse in adults receiving a dUCB TCF RIC allogeneic transplantation. This highlights the need to develop immunotherapy approaches allowing for early conversion to full chimerism after this type of transplantation.
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Peterlin
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gastinne
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mahé
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Viviane
authors.initials: V
authors.lastname: Dubruille
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blin
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Le Bourgeois
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.affiliation: Hematology/Biology Department, University Hospital, Nantes, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lodé
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France; Centre de recherche en cancérologie Nantes/Angers, INSERM UMR 892; Centre d'Investigation Clinique en Cancérologie (CI2C), Nantes, France; Onco-haematology Clinical Research Unit, University Hospital, Nantes, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Haematology/Biology, University Hospital, Nantes, France. Electronic address: patrice.chevallier@chu-nantes.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Adults; Chimerism; Double cord blood allogeneic stem cells transplantation; Outcomes; RIC; Relapse; TCF conditioning