Furukawa Miki, Ikeda Kazuhiko, Ohkawara Hiroshi, Saito Shunichi, Takahashi Hiroshi, Ueda Koki, Matsumoto Hayato, Hashimoto Yuko, Ohto Hitoshi, Ogawa Kazuei, Takeishi Yasuchika
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.
Int J Hematol. 2015 Oct;102(4):498-505. doi: 10.1007/s12185-015-1805-1. Epub 2015 May 15.
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.
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。
