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使用莫格利珠单抗进行自体干细胞移植后,急性白血病期CCR4阳性γδ外周T细胞淋巴瘤持续完全缓解

Persistent complete remission of acute leukemic-phase CCR4-positive gamma-delta peripheral T-cell lymphoma by autologous stem cell transplantation with mogamulizumab.

作者信息

Furukawa Miki, Ikeda Kazuhiko, Ohkawara Hiroshi, Saito Shunichi, Takahashi Hiroshi, Ueda Koki, Matsumoto Hayato, Hashimoto Yuko, Ohto Hitoshi, Ogawa Kazuei, Takeishi Yasuchika

机构信息

Department of Cardiology and Hematology, Fukushima Medical University, 1 Hikariga-oka, Fukushima, Fukushima, 960-1295, Japan.

Department of Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.

出版信息

Int J Hematol. 2015 Oct;102(4):498-505. doi: 10.1007/s12185-015-1805-1. Epub 2015 May 15.

Abstract

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), frequently shows a poor outcome. Especially, expressions of CC chemokine receptor 4 (CCR4) and γδ T-cell receptor (TCR) are associated with worse prognosis in PTCL-NOS. We here report successful treatment with autologous peripheral blood stem cell transplantation (auto-PBSCT) combined with anti-CCR4 antibody mogamulizumab for a very rare case of CCR4+γδTCR+ PTCL-NOS that coexisted with Hodgkin's lymphoma. PTCL-NOS in this patient progressed to leukemic phase, whereas Hodgkin's lymphoma disappeared with standard chemotherapies within 4 years of the initial diagnosis. Leukemic-phase PTCL-NOS was refractory to several chemotherapies. However, auto-PBSCT following high-dose chemotherapy combined with pre- and post-transplant mogamulizumab, which is a humanized monoclonal antibody to CCR4, provided persistent complete remission of PTCL-NOS, despite residual γδTCR+ in the transplanted stem cell product, suggesting a purging effect of mogamulizumab. At 15 months after transplantation, we also found markedly fewer effector regulatory T cells, which may have contributed to prolonged remission. This case suggests that autologous stem cell transplantation combined with mogamulizumab may have a potential to cure T-cell neoplasms that express CCR4 including leukemic-phase PTCL-NOS.

摘要

外周T细胞淋巴瘤,非特殊类型(PTCL-NOS),通常预后较差。特别是,CC趋化因子受体4(CCR4)和γδT细胞受体(TCR)的表达与PTCL-NOS的不良预后相关。我们在此报告了一例非常罕见的CCR4+γδTCR+ PTCL-NOS与霍奇金淋巴瘤共存的病例,采用自体外周血干细胞移植(auto-PBSCT)联合抗CCR4抗体莫加莫拉izumab成功治疗。该患者的PTCL-NOS进展至白血病期,而霍奇金淋巴瘤在初始诊断后4年内经标准化疗消失。白血病期PTCL-NOS对多种化疗均耐药。然而,大剂量化疗后进行auto-PBSCT,并在移植前后使用莫加莫拉izumab(一种针对CCR4的人源化单克隆抗体),尽管移植的干细胞产品中仍有残留的γδTCR+,但PTCL-NOS仍持续完全缓解,提示莫加莫拉izumab具有清除作用。移植后15个月,我们还发现效应调节性T细胞明显减少,这可能有助于延长缓解期。该病例表明,自体干细胞移植联合莫加莫拉izumab可能有治愈表达CCR4的T细胞肿瘤(包括白血病期PTCL-NOS)的潜力。

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