Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma
Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma
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DOI：
10.1200/jco.2005.00.240
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发表时间：
2005-04-01
影响因子：
45.3
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
--
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
目的我们研究淋巴细胞清除化疗联合自体肿瘤反应性淋巴细胞过继转移治疗难治性转移性黑色素瘤患者。患者和方法35例转移性黑色素瘤患者，除1例患者外，所有患者均患有高剂量白细胞介素（IL）-2治疗难治性疾病，许多患者在化疗后病情进展，接受了两天环磷酰胺（60 mg/kg）和五天氟达拉滨（25 mg/m2）的淋巴细胞清除预处理。在氟达拉滨的最后一次剂量的第二天，所有患者接受自体肿瘤反应性细胞输注，快速扩增的肿瘤浸润淋巴细胞培养物和高剂量IL-2 therapy.Results十八（51%）的35例治疗患者经历了客观的临床反应，包括三个正在进行的完全反应和15个部分反应，平均持续时间为11.5 +/- 2.2个月。消退部位包括肺、肝、淋巴结、脑以及皮肤和皮下组织的转移。治疗毒性包括化疗的预期血液学毒性，包括中性粒细胞减少症、血小板减少症和淋巴细胞减少症，大剂量IL-2治疗的一过性毒性，两名患者出现肺孢子虫肺炎，一名患者出现EB病毒，结论化疗联合高亲和力的抗肿瘤淋巴细胞转移可显著促进肿瘤消退。IL-2难治性转移性黑色素瘤患者。
Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma.Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL) -2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m(2)). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy.Results Eighteen (51 %) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 +/- 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation.Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma.