LAUSR

Dear Editor, We encountered a 55-year-old female with a 12-year history of rheumatoid arthritis (RA) and she had been taking methotrexate (MTX) for 10 years. Although MTX resulted in a good control of the RA activity, she presented with multiple cervical and axillary lymphadenopathy. A left axillary lymph node biopsy was performed, and a histopathological examination of the biopsy specimen revealed a diagnosis of classical Hodgkin lymphoma (mixed cellularity type). Immunohistochemical staining was positive for CD15 and CD30. MTX-associated lymphoproliferative disorder (MTX-LPD) was suspected and MTX treatment was discontinued immediately. However, the lymphoma failed to regress spontaneously and additional chemotherapy was required to avoid disease progression. She underwent eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and achieved complete remission (CR). However, 1 year after achieving CR, positron emission tomography/computed tomography (PETCT) showed the uptake of F-18 fluorodeoxyglucose (FDG) in her right axillary lymph nodes and left obturator lymph nodes (Fig. 1). These findings suggested a relapse of lymphoma, and salvage chemotherapy was required. PET-CT also showed the uptake of FDG in multiple joints, including the bilateral shoulders, wrists, and knees. Increasing RA disease activity was also suspected. Her RA symptoms, such as arthralgia and swollen joints, also worsened despite receiving 10 mg of prednisolone instead of MTX. The C-reactive protein (CRP) level rose to 10.0 mg/dl and the Disease Activity Score-28 with CRP (DAS-28-CRP) was 4.78, indicating high disease activity. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate (ADC), was thus started as salvage therapy for relapsed lymphoma. After four cycles of BV, PET-CT showed complete metabolic remission. Interestingly, the FDG uptake in her joints also disappeared after the treatment of BV (Fig. 2), and her RA symptoms improved with BV treatment. The CRP level decreased to 0.1 mg/ dl and DAS-28-CRP was reduced to 1.21, indicating clinical remission. After 12 cycles of BV, PET-CT showed no evidence of lymphoma recurrence, and her RA continued to be in remission. MTX-LPD is a lymphoproliferative disease or lymphoma in patients treated with MTX for autoimmune diseases, such as RA. Some patients with MTX-LPDs show spontaneous regression after the withdrawal of MTX [1]. In patients with MTX-LPD that do not spontaneously regress, additional chemotherapy is required to avoid disease progression. MTX-LPD have various histopathological features. The most commonly reported cases are diffuse large B cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL) types [2]. MTX discontinuation is often ineffective in CHL-type MTX-LPD patients for disease control compared with DLBCL-type patients, and most CHL-type MTX-LPD patients require additional chemotherapy [3]. Although BV is a promising agent for relapsed/refractory CHL, there is little evidence of the e f fec t iveness of BV for CHLtype MTX-LPD. Furthermore, the efficacy of BV for RA is also unclear. To our knowledge, only one case of CHL-type MTX-LPD treated with BV has been reported in the literature [4]. * Tomonori Nakazato n–[email protected]