title: Allogeneic cell-mediated and cytokine-activated immunotherapy for malignant lymphoma at the stage of minimal residual disease after autologous stem cell transplantation.
abstract: Immunocompetent donor-derived T lymphocytes play a crucial role in the elimination of residual leukemic cells post allogeneic bone marrow transplantation. Because this graft versus leukemia (GVL) effects is absent after autologous stem cell transplantation (ASCT), a high rate of relapse ensues. We introduced cell-mediated immunotherapy at the stage of minimal residual disease in lymphoma patients to help effect a GVL-like reaction by adoptive transfer of immunocompetent human leukocyte antigen-matched donor peripheral blood lymphocytes (PBL). Thirteen consecutive patients with high-risk lymphoma were treated with allogeneic cell therapy (AlloCT) after having undergone ASCT. In the absence of graft-versus-host disease, cell therapy-induced graft-versus-lymphoma reaction was amplified by human recombinant interleukin 2 (rIL-2) during 3 days to activate donor PBL in vivo, followed by infusion of in vitro rIL-2 activated donor lymphocytes combined with 3-day rIL-2 therapy. Nine of the patients underwent the treatment protocol well. In the four other patients, in whom the AlloCT resulted in marrow aplasia due to elimination of host hematopoietic cells, treatment with donor marrow cell infusion without further conditioning was performed. Adoptive cell therapy in the form of AlloCT may turn out to be an effective therapeutic modality for the treatment of resistant residual disease in lymphoma patients.
authors.affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: A
authors.initials: A
authors.lastname: Ackerstein
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.forename: A
authors.initials: A
authors.lastname: Amar
authors.forename: E
authors.initials: E
authors.lastname: Naparstek
authors.forename: G
authors.initials: G
authors.lastname: Varadi
authors.forename: J
authors.initials: J
authors.lastname: Kapelushnik
authors.forename: S
authors.initials: S
authors.lastname: Samuel
authors.forename: T
authors.initials: T
authors.lastname: Pugatsch
authors.forename: C
authors.initials: C
authors.lastname: Brautbar
authors.forename: S
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D016026:Bone Marrow Transplantation; D002452:Cell Count; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000628:therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins