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重复输注自体细胞因子诱导的杀伤细胞治疗老年血液系统恶性肿瘤的临床研究。

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

机构信息

Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Hematol Oncol. 2012 Sep;30(3):115-22. doi: 10.1002/hon.1012. Epub 2011 Aug 23.

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.

摘要

老年人群易患血液系统恶性肿瘤,且对细胞毒性药物不耐受。因此,探索一种安全可靠的化疗以外的策略对于改善老年血液系统恶性肿瘤患者的预后至关重要。我们评估了自体细胞因子诱导的杀伤(CIK)细胞联合重组人白细胞介素 2(rhIL-2)治疗老年血液系统恶性肿瘤的安全性和有效性。从 20 例老年血液系统恶性肿瘤患者中分离外周血单个核细胞,然后用干扰素 γ、rhIL-2 和 CD3 单克隆抗体进行预刺激。将自体 CIK 细胞(2-3×10(9))回输给患者,然后连续 10 天皮下注射 IL-2(1 mU/天)。该方案每 4 周重复一次。评估宿主细胞免疫功能、肿瘤相关生物学参数、影像学特征、疾病状况、生活质量和生存时间。14 例患者接受了 8 个周期的输注,6 例患者接受了 4 个周期的输注。未观察到不良反应。自体 CIK 细胞输注后,CD3(+)、CD3(+)CD8(+)和 CD3(+)CD56(+)细胞的百分比显著增加(p<0.05),血清β2 微球蛋白和乳酸脱氢酶(LDH)水平明显降低(p<0.05)。癌症相关症状明显缓解,生活质量得到改善(p<0.01)。11 例患者达到完全缓解,7 例患者持续部分缓解,2 例患者病情稳定。随访结束时,平均生存时间为 20 个月。自体 CIK 细胞联合 rhIL-2 治疗老年血液系统恶性肿瘤安全有效。

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