International Journal of Hematology

DOI: 10.1007/s12185-018-2552-x Pages: 1-7

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

1. Karatsu Red Cross Hospital, Department of Internal Medicine

2. Saga University, Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine

3. Kyoto University Graduate School of Medicine, Department of Hematology/Oncology

4. Repertoire Genesis Inc

5. Karatsu Red Cross Hospital, Department of Pathology

6. BITS Co. Ltd

7. Sagamihara National Hospital, Department of Clinical Immunology, Clinical Research Center for Allergy and Rheumatology

8. Kurume University School of Medicine, Department of Pathology

Correspondence to:
Takero Shindo
Tel: +81-75-751-4964
Email: takeros@kuhp.kyoto-u.ac.jp

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Abstract

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.

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