Kamachi Kazuharu, Shindo Takero, Miyahara Masaharu, Kitaura Kazutaka, Akashi Michiaki, Shin-I Tadasu, Suzuki Ryuji, Oshima Koichi, Kimura Shinya
Department of Internal Medicine, Karatsu Red Cross Hospital, Karatsu, Japan.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Int J Hematol. 2019 Feb;109(2):221-227. doi: 10.1007/s12185-018-2552-x. Epub 2018 Oct 27.
Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C-C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein-Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.
成人T细胞白血病(ATL)是一种侵袭性成熟T细胞恶性肿瘤,预后较差。抗C-C基序趋化因子受体4(CCR4)抗体莫加莫单抗(moga)可减少ATL细胞并诱导多克隆T细胞重建;然而,ATL病例通常仍具有耐药性,moga有时会导致致命的免疫病理学。爱泼斯坦-巴尔病毒(EBV)相关的B细胞淋巴瘤发生于严重免疫功能低下的患者,尤其与T细胞免疫受损有关。在此,我们报告1例接受过传统化疗加moga治疗的ATL患者,随后发生了中枢神经系统EBV相关弥漫性大B细胞淋巴瘤(DLBCL)。基于二代测序的T细胞受体库分析鉴定出残留的异常克隆,并显示即使在moga治疗后,多克隆T细胞的重建也不完全。此外,发现moga治疗后出现的皮疹中含有ATL克隆。该病例提示,moga有限的治疗效果和不完全的T细胞重建与严重受损的T细胞免疫及随后发生的EBV相关DLBCL有关。