Jeffrey E Rubnitz1,2, Hiroto Inaba1,2, Guolian Kang3, Kwan Gan4, Christine Hartford4,2, Brandon M Triplett4,2, Mari Dallas4,2, David Shook4,2, Tanja Gruber1,2, Ching-Hon Pui1,5,2, Wing Leung4,2. 1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 2. Department of Pediatrics, University of Tennessee Health Science Center, College of, Medicine, Memphis, Tennessee. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee. 5. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract
BACKGROUND: Novel therapies are needed for children with relapsed or refractory leukemia. We therefore tested the safety and feasibility of haploidentical natural killer cell therapy in this patient population. PROCEDURE: Twenty-nine children who had relapsed or refractory leukemia were treated with chemotherapy followed by the infusion of haploidentical NK cells. Cohort 1 included 14 children who had not undergone prior allogeneic hematopoietic cell transplantation (HCT), whereas Cohort 2 included 15 children with leukemia that had relapsed after HCT. RESULTS: Twenty-six (90%) NK donors were KIR mismatched (14 with one KIR and 12 with 2 KIRs). The peak NK chimerism levels were >10% donor in 87% of the evaluable recipients. In Cohort 1, 10 had responsive disease and 12 proceeded to HCT thereafter. Currently, 5 (36%) are alive without leukemia. In Cohort 2, 10 had responsive disease after NK therapy and successfully proceeded to second HCT. At present, 4 (27%) are alive and leukemia-free. The NK cell infusions and the IL-2 injections were well-tolerated. CONCLUSIONS: NK cell therapy is safe, feasible, and should be further investigated in patients with chemotherapy-resistant leukemia.
BACKGROUND: Novel therapies are needed for children with relapsed or refractory leukemia. We therefore tested the safety and feasibility of haploidentical natural killer cell therapy in this patient population. PROCEDURE: Twenty-nine children who had relapsed or refractory leukemia were treated with chemotherapy followed by the infusion of haploidentical NK cells. Cohort 1 included 14 children who had not undergone prior allogeneic hematopoietic cell transplantation (HCT), whereas Cohort 2 included 15 children with leukemia that had relapsed after HCT. RESULTS: Twenty-six (90%) NK donors were KIR mismatched (14 with one KIR and 12 with 2 KIRs). The peak NK chimerism levels were >10% donor in 87% of the evaluable recipients. In Cohort 1, 10 had responsive disease and 12 proceeded to HCT thereafter. Currently, 5 (36%) are alive without leukemia. In Cohort 2, 10 had responsive disease after NK therapy and successfully proceeded to second HCT. At present, 4 (27%) are alive and leukemia-free. The NK cell infusions and the IL-2 injections were well-tolerated. CONCLUSIONS: NK cell therapy is safe, feasible, and should be further investigated in patients with chemotherapy-resistant leukemia.
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