Repeated transfusions of autologous cytokine‐induced killer cells for treatment of haematological malignancies in elderly patients: a pilot clinical trial

Abstract

The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy exclusive of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. We evaluated the safety and the efficacy of autologous cytokine-induced killer (CIK) cells combined with recombinant human interleukin 2 (rhIL-2) in the treatment of haematological malignancies in elderly patients. Peripheral blood mononuclear cells were isolated from 20 elderly patients with haematological malignancies, then augmented by priming with interferon gamma, rhIL-2 and CD3 monoclonal antibody. The autologous CIK cells (2-3 × 10(9)) were transfused back to patients, followed by a subcutaneous injection of IL-2 (1 mU/day) for 10 consecutive days. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 8 cycles of transfusion and 6 received 4 cycles. No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum β2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01). Complete remission was observed in 11 patients, persistent partial remission in 7 patients and stable disease in 2 patients. At the end of follow-up, the mean survival time was 20 months. Transfusion with autologous CIK cells plus rhIL-2 treatment is safe and effective for treating haematological malignancies in elderly patients.

Adoptive Immunotherapy Strategies with Cytokine-Induced Killer (CIK) Cells in the Treatment of Hematological Malignancies

“…As the next step, Yang et al [37] enrolled 20 patients in a phase I trial. The patients’ age ranged from 57–93 years with a median age of 83 years.…”

“…Among them, nine were diagnosed with lymphoma, five with MDS, two with multiple myeloma (MM), three with chronic lymphocytic leukemia (CLL) and one with acute myeloid leukemia (AML). Once more, Yang et al [37] combined the CIK cell infusions (2–3 × 10 9 ) with subcutaneous injections of IL-2 (1 mU/day) for 10 consecutive days after each infusion. Six patients received four cycles, and the remaining 14 were administered eight cycles.…”

“…In detail, five of nine lymphoma patients experienced an improved clinical state with even three patients improving from progressive disease to CR, while four patients could maintain their previous disease state as determined prior to CIK cell treatment; the disease state of all remaining eleven patients improved, with nine of them even achieving CR or PR. Additionally, the QOL markedly improved as demonstrated by an increased Karnofsky score from 57% (40%–90%) to 83% (60%–100%) [37]. Subsequently the same group reported on nine geriatric patients (aged from 65–90 years) with diffuse large B-cell lymphoma, which were pretreated with four courses of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride (Hydroxydaunomycin), Vincristine Sulfate (Oncovin) and Prednisone) before CIK cell treatment.…”

Cytokine-induced killer (CIK) cells in cancer immunotherapy: report of the international registry on CIK cells (IRCC)

“…(2012a, b),Laport et al (2011),Introna et al (al. (2012a, b),Laport et al (2011),Introna et al (2007Introna et al ( , 2010,Yang et al (2012Yang et al ( , 2014b,Wang et al al. (2011,Cai et al Wolf et al (1999), Linn et al (2012a, b), Laport et al (2011), Yang et al (2010, 2012), Leemhuis et al (2005), Huang et al (2006), Lu et al (2012), Zhang et al (2012), Olioso et al al.…”

Innovative and propagable translational research model established for cell-based therapy at Chinese PLA General Hospital

“…For example, chemotherapeutic agents or glucocorticoids were applied within one week of immune cell transfusion. Overall, fewer than 50 cases with integrated laboratory and clinical data were available for analysis (Yang et al, 2012;Lu et al, 2012;Wang et al, 2013;Sheng et al, 2009). Our five-year practice revealed that this CPC-centered and multidisciplinary collaborative translational approach provided a high-input, low-output model, at least under the current conditions of Chinese hospitals.…”