title: A pilot study of allogeneic cellular therapy for patients with advanced hematologic malignancies.
abstract: Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood stem cells administered after very low dose total body irradiation (TBI) (100cGy). The donor cells were anticipated to be rejected, so no graft-versus-host (GVHD) prophylaxis was used. Patients with persistent disease beyond 8 weeks could be further treated with infusions of irradiated haploidentical donor cells. Of the 10 patients enrolled in the study, durable engraftment of allogeneic cells was seen in one patient. Two patients with resistant relapsed acute myelogenous leukemia (AML) had a disease response. Analysis of T cell reactivity from one patient who achieved a complete response but did not have durable engraftment of donor cells indicated that disease response was associated with the generation of host-derived anti-leukemic cytotoxic CD8+ T cells that reacted with an AML-associated proteinase 3 epitope. Results from this patient suggest that allogeneic therapy induced a host anti-tumor response associated with cytotoxic T cells reactive with a low affinity self-antigen.
authors.affiliation: The Cancer Institute of New Jersey, Department of Medicine, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, New Brunswick, NJ 08901, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Medina
authors.forename: Mecide
authors.initials: M
authors.lastname: Gharibo
authors.forename: Philip
authors.initials: P
authors.lastname: Savage
authors.forename: Alan
authors.initials: A
authors.lastname: Cohler
authors.forename: Mercy
authors.initials: M
authors.lastname: Kuriyan
authors.forename: Binaifer
authors.initials: B
authors.lastname: Balsara
authors.forename: Monika
authors.initials: M
authors.lastname: Anand
authors.forename: Dale
authors.initials: D
authors.lastname: Schaar
authors.forename: Tracy
authors.initials: T
authors.lastname: Krimmel
authors.forename: Kara
authors.initials: K
authors.lastname: Saggiomo
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Manago
authors.forename: Lois
authors.initials: L
authors.lastname: Talty
authors.forename: Liesel
authors.initials: L
authors.lastname: Dudek
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grospe
authors.forename: Arnold
authors.initials: A
authors.lastname: Rubin
authors.forename: Roger K
authors.initials: RK
authors.lastname: Strair
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017252:CD3 Complex / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000601:surgery; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000601:surgery; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014019:Tissue Donors; D015626:Tissue Expansion / Q000379:methods; D020858:Tissue and Organ Harvesting / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D017252:CD3 Complex