title: Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery.
abstract: Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34(+) cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.
authors.affiliation: Division of Hematology and Bone Marrow Transplantation, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Dodero
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
authors.forename: Anna
authors.initials: A
authors.lastname: Raganato
authors.forename: Antonio
authors.initials: A
authors.lastname: Vendramin
authors.forename: Lucia
authors.initials: L
authors.lastname: Farina
authors.forename: Francesco
authors.initials: F
authors.lastname: Spina
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Simona
authors.initials: S
authors.lastname: Di Terlizzi
authors.forename: Marco
authors.initials: M
authors.lastname: Milanesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Longoni
authors.forename: Lorenza
authors.initials: L
authors.lastname: Gandola
authors.forename: Claudia
authors.initials: C
authors.lastname: Lombardo
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016827:CD8 Antigens / Q000378:metabolism*; D005240:Feasibility Studies; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D016130:Immunophenotyping; D008212:Lymphocyte Depletion / Q000379:methods*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016827:CD8 Antigens; D007143:Immunoglobulin Heavy Chains; D011948:Receptors, Antigen, T-Cell