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  • Title: The emergence of CD20-/CD19- tumor cells after rituximab therapy for Epstein-Barr virus-associated post-transplant lymphoproliferative disorder complicated with hemophagocytic lymphohistiocytosis.
    Author: Yamamoto N, Nishimura N, Takeuchi M, Ito T, Yokozaki H, Hirase S, Kubokawa I, Mori T, Yanai T, Hayakawa A, Takeshima Y, Nishio H, Matsuo M, Imadome K, Iijima K.
    Journal: Eur J Pediatr; 2014 Dec; 173(12):1615-8. PubMed ID: 24169729.
    Abstract:
    Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized aggressive disease commonly associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although rituximab (RTX) is incorporated into the first-line therapy for EBV-PTLD patients, the outcome of the clinically overt disease is still not optimal mainly due to the regrowth of tumor cells. The proliferation of CD20-/CD19+ tumor cells is increasingly reported in RTX-treated EBV-PTLD patients, whereas the emergence of CD20-/CD19- tumor cells is barely recognized. Here, we report a fatal case of an 18-year-old patient who developed EBV-PTLD after allogeneic HSCT for anaplastic large-cell lymphoma. On day 60 after HSCT, the patient developed abdominal pain, watery diarrhea, and low-grade fever. Colon biopsy revealed the proliferation of CD20+/CD19+/EBV-encoded RNA (EBER)+ tumor cells, and an increase of EBV DNA was detected in peripheral blood (PB). He was treated with RTX for EBV-PTLD and was cleared of EBV DNA in PB. However, he manifested high-grade fever, pancytopenia, and elevated soluble interleukin-2 receptor with a prominent hemophagocytosis in bone marrow aspirates and was treated with etoposide for hemophagocytic lymphohistiocytosis (HLH) complication. He then developed EBV DNA positivity in PB and finally died of Bacteroides fragilis sepsis subsequent to bloody stool and ileus on day 163. Autopsy revealed erosion and bleeding in the whole colon with the proliferation of CD20-/CD19-/EBER+ tumor cells. Immunohistochemical analysis uncovered the CD3-/CD56-/CD79a+/CD79b+ B-cell origin of tumor cells. This case clinically demonstrates the removal of both CD20 and CD19 antigens from EBER+ B cells in an RTX-treated EBV-PTLD patient with HLH complication.
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