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Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study

From the Laboratory of Cellular and Gene Therapy "G. Lanzani", Ospedali Riuniti di Bergamo, Bergamo, Italy (MI, GB, EC, MF, JG); Division of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy (AMB, RB, OS, AG, TB, AR); Laboratory of Cellular and Gene Therapy "S. Verri", University of Milano Bicocca, Ospedale S. Gerardo, Monza, Italy (ED, GG, GD, EB, AB); Institute of Internal Medicine, University of Milano Bicocca, Monza, Italy (MP, EMP); Division of Hematology and Bone Marrow Transplant Centre, Ospedale Businco, Cagliari, Italy (DB)

Correspondence:Martino Introna, Laboratory of Cellular and Gene Therapy "G. Lanzani", c/o Presidio Matteo Rota, via Garibaldi 11–13, Ospedali Riuniti di Bergamo, 24128 Bergamo, Italy. E-mail: mintrona{at}ospedaliriuniti.bergamo.it

Background and Objectives: Cytokine-induced killer (CIK) cells have shown anti-leukemic activity and little graft-versus-host disease (GVHD) in several animal models. The safety of these cells in autologous settings has been shown. We performed a phase I study of allogeneic (donor’s) CIK cells in patients relapsing after allogeneic haematopoietic stem cell transplantation (HSCT).

Design and Methods: Eleven patients with acute myelogenous leukemia (n=4), Hodgkin’s disease (n=3), chronic myelomonocytic leukemia, (n=1), pre-B acute lymphoblastic leukemia (n=1) and myelodysplasia (n=2), all of whom had relapsed after sibling (n=6) or matched unrelated donor (n=5) HSCT, entered this study.

Results: Before CIK administration, six patients had received other salvage treatments including chemotherapy (n=5), radiotherapy (n=1) and unmanipulated donor lymphocytes (n=6) without any significant tumor response. The median number of CIK infusions was two (range 1–7) and the median number of total CIK cells was 12.4 x 10⁶/kg (range 7.2–87.4). The infusions were well tolerated and no acute or late infusion-related reactions were recorded. Acute GVHD (grade I and II) was observed in four patients, 30 days after the last CIK infusion, and progressed into extensive chronic GVHD in two cases. Disease progression and death occurred in six patients. One patient had stable disease, one had hematologic improvement and three achieved complete responses.

Interpretation and Conclusions: This study shows that the production of allogeneic CIK cells is feasible under clinical-grade conditions, well tolerated and may contribute to clinical responses.

Key words: CIK, DLI, GVHD, allo HSCT.

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