title: Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies.
abstract: We evaluated a photodepletion technique to selectively deplete host-reacting T cells from human leukocyte antigen (HLA)-matched sibling stem cell transplantations with the goal of reducing posttransplantation immunosuppression to improve antimalignancy effects postallografting. Donor lymphocytes were stimulated with irradiated expanded recipient T lymphocytes in an ex vivo mixed lymphocyte reaction. Alloactivated T cells preferentially retaining the photosensitizer 4,5-dibromorhodamine 123 (TH9402) were eliminated by exposure to visible light. Twenty-four patients with hematologic malignancies (16 high risk) conditioned with fludarabine, cyclophosphamide, and totalbody irradiation received a CD34-selected stem cell allograft from an HLA-matched sibling along with 5 × 10(6)/kg selectively depleted donor T cells. Low-dose cyclosporine was used for posttransplantation immunosuppression. Eleven patients survived at a median of 30 months. Probabilities (± SEM) for overall and disease-free survival are 39% ± 12% and 30% ± 12%, respectively, whereas grade III-IV acute graft-versus-host disease (aGVHD) was 13% ± 7%. Six patients relapsed, with a relapse probability of 27% ± 10%. These results suggest that selectively photodepleted allografts in matched sibling transplantations followed by low-dose immunosuppression may protect against severe aGVHD but is associated with delayed immune recovery.
authors.affiliation: Department of Internal Medicine II, Division of Hematology, University Hospital of Wuerzburg, Wuerzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mielke
authors.forename: Zachariah A
authors.initials: ZA
authors.lastname: McIver
authors.forename: Aarthy
authors.initials: A
authors.lastname: Shenoy
authors.forename: Vicki
authors.initials: V
authors.lastname: Fellowes
authors.forename: Hahn
authors.initials: H
authors.lastname: Khuu
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Richard
authors.initials: R
authors.lastname: Childs
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Koklanaris
authors.forename: Janice
authors.initials: J
authors.lastname: Haggerty
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.forename: Katie
authors.initials: K
authors.lastname: Rezvani
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens