Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study
Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study
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DOI：
10.3324/haematol.11132
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发表时间：
2007-07-01
期刊：
影响因子：
10.1
通讯作者：
Rambaldi, Alessandro
中科院分区：
文献类型：
--
作者：
Introna, Martino;Borleri, Gianmaria;Rambaldi, Alessandro
背景与目的细胞因子诱导的杀伤细胞（CIK）在几种动物模型中显示出抗白血病活性和较少的移植物抗宿主病（GVHD）。这些细胞在自体环境中的安全性已经得到证实。我们对异体造血干细胞移植（HSCT）后复发的患者进行了一项异体（供体）CIK细胞的I期研究。设计与方法：急性髓性白血病（n=4）、霍奇金病（n=3）、慢性髓单核细胞白血病（n=1）、b前急性淋巴细胞白血病（n=1）和骨髓增生异常（n=2）患者均在兄弟姐妹（n=6）或匹配的非亲属供体（n=5） HSCT后复发，进入本研究。结果在给予CIK治疗前，6例患者接受了化疗（n=5）、放疗（n=1）和未经处理的供体淋巴细胞（n=6）等其他补救性治疗，均未见明显肿瘤反应。注射CIK的中位数为2次（范围1-7），CIK细胞总数的中位数为12.4 × 10.6 /kg（范围7.2-87.4）。输注耐受良好，无急性或晚期输注相关反应记录。在最后一次注射CIK后30天，4例患者出现急性GVHD （I级和II级），2例进展为广泛的慢性GVHD。6例患者出现疾病进展和死亡。1例病情稳定，1例血液学改善，3例完全缓解。这项研究表明，在临床级条件下，异体CIK细胞的产生是可行的，耐受性良好，可能有助于临床反应。本研究表明，在临床级条件下，异体CIK细胞的产生是可行的，耐受性良好，可能有助于临床反应。
Background and ObjectivesCytokine-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 MethodsEleven 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.ResultsBefore 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 l0 6/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. This study shows that the production of allogeneic CIK cells is feasible under clinical- grade conditions, well tolerated and may contribute to clinical responses.Interoretation and ConclusionsThis study shows that the production of allogeneic CIK cells is feasible under clinical- grade conditions, well tolerated and may contribute to clinical responses.