Fuji Shigeo, Shindo Takero
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Department of Hematology, Respiratory Medicine and Oncology, Saga University School of Medicine, Saga, Japan.
Stem Cell Investig. 2016 Oct 31;3:70. doi: 10.21037/sci.2016.09.13. eCollection 2016.
Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory. The anti-CCR4 antibody mogamulizumab (moga) has been recently approved for ATL in Japan, and it is effective in a significant proportion of patients with refractory or relapsed ATL. However, there are major concerns about the harmful influences of pretransplant moga on the immune reconstitution after allo-HSCT. Specifically, moga depletes regulatory T cells (Tregs) for at least a few months, which may increase the risk of graft-versus-host disease (GVHD) after allo-HSCT. A recent retrospective study from Japan clearly showed that pretransplant moga increased the risk of severe and steroid-refractory GVHD, which led to increases in non-relapse mortality and overall mortality. To improve the overall clinical outcome in patients with relapsed or refractory ATL, more studies are needed to incorporate moga without increasing adverse effects on the clinical outcome after allo-HSCT. In this review, we aim to provide an updated summary of the research related to moga and allo-HSCT.
成人T细胞白血病/淋巴瘤（ATL/ATLL）是一种与1型人类嗜T淋巴细胞病毒（HTLV-1）相关的外周T细胞肿瘤。即使是目前强度最大的化疗方案改良LSG15（mLSG15，VCAP-AMP-VECP），临床结局也很惨淡，中位总生存期仅约1年。尽管异基因造血干细胞移植（allo-HSCT）可能使一部分侵袭性ATL患者获得长期缓解，但难治性或复发性ATL患者的临床结局仍不尽人意。抗CCR4抗体莫格利珠单抗（moga）最近在日本被批准用于治疗ATL，对相当一部分难治性或复发性ATL患者有效。然而，人们主要担心移植前使用moga对allo-HSCT后免疫重建的有害影响。具体而言，moga会使调节性T细胞（Tregs）减少至少几个月，这可能会增加allo-HSCT后移植物抗宿主病（GVHD）的风险。日本最近一项回顾性研究清楚地表明，移植前使用moga会增加严重和激素难治性GVHD的风险，进而导致非复发死亡率和总死亡率上升。为改善复发或难治性ATL患者的总体临床结局，需要开展更多研究，在不增加对allo-HSCT后临床结局不利影响的情况下纳入moga。在本综述中，我们旨在提供与moga和allo-HSCT相关研究的最新总结。
