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Clearance of Hematologic Malignancies by Allogeneic Cytokine-Induced Killer Cell or Donor Lymphocyte Infusions
Institution:1. Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescents, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany;2. Pediatric Oncology, Department of Pediatric and Adolescent Medicine, University Hospital Ulm, Ulm, Germany;3. Clinic of Pediatric Oncology, Hematology and Immunology, University Children''s Hospital Düsseldorf, Düsseldorf, Germany;4. Hematology/Oncology, Department of Internal Medicine, University Hospital Frankfurt, Frankfurt am Main, Germany;5. German Red Cross Blood Donor Service Baden-Württemberg-Hessen and Institute for Transfusion Medicine and Immunohematology, Department of Cellular Therapeutics/Cell Processing, Goethe University Frankfurt, Frankfurt am Main, Germany;6. Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington
Abstract:Well-established donor lymphocyte infusion (DLI) and novel cytokine-induced killer (CIK) cell therapy for the treatment of relapsing hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT) were compared with respect to feasibility, safety, and efficacy. Altogether, a total of 221 infusions were given to 91 patients (DLI, n = 55; CIK, n = 36). T cell recovery was significantly improved after CIK cell therapy (P < .0001). Although patients with CIK cell treatment showed a significantly worse prognosis at the time of HSCT (risk score, 1.7 versus 2.1; P < .0001), DLI and CIK cell therapy induced complete remission (CR) in 29% and 53% patients, respectively, whereas relapse occurred in 71% and 47%. In both groups, all patients with overt hematologic relapse at the time of immunotherapy (DLI, n = 11; CIK, n = 8) succumbed to their disease, while 36% and 68% patients with DLI or CIK cell therapy applied due to molecular relapse or active disease at the time of transplantation achieved CR. The 6-month overall survival rate in the latter patients was 57% and 77%, respectively, with a median follow-up of 27.9 months (range, .9 to 149.2 months). The 6-month cumulative incidence of relapse was 55% and 22% in patients who received DLI and CIK cell therapy, respectively (P = .012). Acute graft-versus-host disease developed in 35% of the patients who received DLI and in 25% of those who received CIK. No transfusion-related deaths occurred. These data, while underscoring the therapeutic value of conventional DLI, suggest the improved safety and to a certain extent efficacy of CIK cell therapy for patients at high risk for post-transplantation relapse of various hematologic malignancies.
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