LAUSR

Dear Editor, Ep s t e i n -Ba r r v i r u s (EBV) a s s o c i a t e d po s t transplantation lymphoproliferative disorders (PTLD) represent a heterogeneous group of EBV-driven abnormal lymphoid proliferations occurring after allogeneic hematopoietic stem cell transplantation [1–3]. Although several therapeutic strategies, such as reduction of immunosuppressive agents, rituximab monotherapy, multiagent chemotherapy, and infusion of EBV-specific cytotoxic T lymphocytes (CTLs), have somewhat improved the outcome of patients with PTLD, there is a concern that PTLD is still significantly associated with high mortality. The use of immune checkpoint inhibitors (iCPIs) has emerged as a promising strategy because of its potential effectiveness in enhancing antitumor immunity. Recently several case reports have been published describing the use of iCPIs to treat patients with aggressive hematological malignancies such as Hodgkin lymphoma [4–6]. However, there is a paucity of data on the safety and efficacy regarding the use of iCPIs before or after allo-HSCT. Although iCPIs can induce an antitumor immune response, there is also a risk of graft-versus-host disease (GVHD). Ijaz A et al. have reported that 14% of the patients who receive iCPIs after allo-HSCT develop acute GVHD and 9% develop chronic GVHD [7]. Therefore, development of GVHD should be considered while applying these agents in the preor post-allo-HSCT settings. Despite the abundant data on the use of iCPIs for the treatment of cHL, only one pediatric case report is available on the use of iCPIs for PTLD [8]. Here we report the first case of successful iCPI use for the treatment of an adult patient with cHL-like PTLD following allo-HSCT. A 58 y e a r o l d woman wa s d i a gno s e d w i t h myelodysplastic syndrome and refractory cytopenia with multilineage dysplasia (MDS-RCMD) with complex karyotype in June 2013. She received bone marrow transplantation from an HLA8/8 allele-matched unrelated donor in March 2014. In March 2018, F fluorodeoxyglucosepositron emission tomography (F-FDG-PET) revealed left supraclavicular and abdominal paraaortic lymphadenopathies (Fig. 1a and b). Biopsy of the supraclavicular lymph node was performed for diagnosis, and the histology showed EBV-associated cHL-like PTLD with the presence of CD15, CD30, and EBER-positive tumor cells. We started administering brentuximab vedotin (BV) every 3 weeks. After six courses of BV, F-FDG-PET/ CT showed complete remission. After 4 months, followup CT study showed paraaortic lymphadenopathy of 20 mm in diameter. The CT-guided biopsy of the lymph node demonstrated the relapse of cHL-like PTLD. FFDG-PET/CT revealed no other lymph node involvement (Ann Arbor stage I). Following the regulatory approval, biweekly administration of nivolumab was started. The starting dose was set to 240 mg/every other week. After four courses, liver toxicity (grade 3) developed, thus we postponed the next course. One month later, the liver function was improved. Therefore, we restarted administering nivolumab at the same dose. After six courses, * Tadakazu Kondo [email protected]