Epstein–Barr virus-related diffuse large B-cell lymphoma in mogamulizumab-treated adult T-cell leukemia with incomplete T-cell reconstitution

• Published in: International journal of hematology Vol. 109; no. 2; pp. 221 - 227
• Main Authors: Kamachi, Kazuharu, Shindo, Takero, Miyahara, Masaharu, Kitaura, Kazutaka, Akashi, Michiaki, Shin-I, Tadasu, Suzuki, Ryuji, Oshima, Koichi, Kimura, Shinya
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.02.2019; Springer Nature B.V
• Subjects: Antibodies; B-cell lymphoma; Case Report; Central nervous system; Chemokine receptors; Chemotherapy; Epstein-Barr virus; Hematology; Immunity; Immunotherapy; Leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Malignancy; Medicine; Medicine & Public Health; Monoclonal antibodies; Next-generation sequencing; Oncology; Sequences; Skin; T cell receptors; Targeted cancer therapy; Viruses; T-cell reconstitution; Mogamulizumab; Adult T-cell leukemia (ATL/ATLL); Epstein–Barr virus-related central nervous system lymphoma
• ISSN: 0925-5710; 1865-3774; 1865-3774
• DOI: 10.1007/s12185-018-2552-x

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.