Brandon M Triplett1,2, Brad Muller1, Guolian Kang3, Ying Li1, Shane J Cross4, Joseph Moen3, Lea Cunningham1,2, William Janssen1, Ewelina Mamcarz1,2, David R Shook1,2, Ashok Srinivasan1,2, John Choi5, Randall T Hayden5, Wing Leung1,2. 1. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA. 2. Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA. 4. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. 5. Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Abstract
BACKGROUND: T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. METHODS: Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. RESULTS: Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P < .001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein-Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3-depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02). CONCLUSION: CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia.
BACKGROUND: T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. METHODS: Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. RESULTS:Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P < .001), and higher T-cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein-Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3-depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02). CONCLUSION: CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia.
Authors: S Chaleff; M Otto; R C Barfield; T Leimig; R Iyengar; J Martin; M Holiday; J Houston; T Geiger; V Huppert; R Handgretinger Journal: Cytotherapy Date: 2007-10-04 Impact factor: 5.414
Authors: D Teschner; E Distler; D Wehler; M Frey; D Marandiuc; K Langeveld; M Theobald; S Thomas; W Herr Journal: Bone Marrow Transplant Date: 2013-08-12 Impact factor: 5.483
Authors: L J Burns; W Miller; C Kandaswamy; T E DeFor; M L MacMillan; J-A Van Burik; D J Weisdorf Journal: Bone Marrow Transplant Date: 2002-12 Impact factor: 5.483
Authors: K S Peggs; W Preiser; P D Kottaridis; N McKeag; N S Brink; R S Tedder; A H Goldstone; D C Linch; S Mackinnon Journal: Br J Haematol Date: 2000-12 Impact factor: 6.998
Authors: Pierre Reusser; Hermann Einsele; John Lee; Liisa Volin; Montserrat Rovira; Dan Engelhard; Jürgen Finke; Catherine Cordonnier; Hartmut Link; Per Ljungman Journal: Blood Date: 2002-02-15 Impact factor: 22.113
Authors: A Pérez-Martínez; M Mora-Rillo; C Ferreras; P Guerra-García; B Pascual-Miguel; C Mestre-Durán; A M Borobia; A J Carcas; J Queiruga-Parada; I García; E Sánchez-Zapardiel; M Gasior; R De Paz; A Marcos; J L Vicario; A Balas; M A Moreno; C Eguizabal; C Solano; J R Arribas; R de Miguel Buckley; R Montejano; B Soria Journal: EClinicalMedicine Date: 2021-08-13
Authors: C Ferreras; B Pascual-Miguel; C Mestre-Durán; A Navarro-Zapata; L Clares-Villa; C Martín-Cortázar; R De Paz; A Marcos; J L Vicario; A Balas; F García-Sánchez; C Eguizabal; C Solano; M Mora-Rillo; B Soria; A Pérez-Martínez Journal: Front Cell Dev Biol Date: 2021-02-25
Authors: Su Han Lum; Sinéad Greener; Inigo Perez-Heras; Daniel Drozdov; Rebecca P Payne; Helen Watson; Kay Carruthers; Robert January; Zohreh Nademi; Stephen Owens; Eleri Williams; Sheila Waugh; Shirelle Burton-Fanning; Timmothy Ronan Leahy; Andrew Cant; Mario Abinun; Terry Flood; Sophie Hambleton; Andrew R Gennery; Mary Slatter Journal: Blood Adv Date: 2022-02-22