Epstein-Barr Virus (EBV)-Induced B-Cell Proliferative Disorder after Chemotherapy in a Patient with Hemophagocytic Lymphohistiocytosis with Associated EBV-Induced T-cell Proliferation

• Published in: Leukemia & lymphoma 2000-05, Vol.37 (5-6), p.593-604
• Main Authors: Suzumiya, Junji, Ohshima, Koichi, Kanda, Motonobu, Kumagawa, Midori, Nagano, Mitsuyuki, Hirata, Masayuki, Nawa, Yukifumi, Tamura, Kazuo, Kikuchi, Masahiro
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-Lymphocytes - pathology; B-Lymphocytes - virology; Blotting, Southern; Brain Neoplasms - etiology; Brain Neoplasms - genetics; Brain Neoplasms - virology; Cell Division; Cell Transformation, Viral; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Doxorubicin - adverse effects; Doxorubicin - analogs & derivatives; Doxorubicin - therapeutic use; Epstein-Bam virus; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Etoposide - adverse effects; Etoposide - therapeutic use; Fatal Outcome; hemophagocytic lymphohistiocytosis; Herpesvirus 4, Human - isolation & purification; Herpesvirus 4, Human - pathogenicity; Histiocytosis, Non-Langerhans-Cell - complications; Histiocytosis, Non-Langerhans-Cell - drug therapy; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; In Situ Hybridization; Interferon-gamma - analysis; Interleukin-10 - analysis; Karyotyping; Lymphocyte Activation; lymphohistiocytosis; Lymphoma, Large B-Cell, Diffuse - etiology; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - virology; lymphoproliferative disorder; Male; malignant lymphoma; Polymerase Chain Reaction; Prednisolone - adverse effects; Prednisolone - therapeutic use; Receptors, Interleukin-2 - analysis; T-Lymphocytes - pathology; T-Lymphocytes - virology; Tumor Necrosis Factor-alpha - analysis; Tumor Virus Infections - complications; VAHS; Vincristine - adverse effects; Vincristine - therapeutic use
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428190009058512

We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ hybridization (ISH) and immunostaining. Southern blot analysis using EBV-TR and immunoglobulin JH probes revealed oligoclonal proliferation of B-cells in each organ involved by abnormal B-lymphoid cells at autopsy. Combined ISH and immunostaining disclosed the presence of EBV in proliferating B-cells. Cytokine analysis during the period of T-cell activation in HLH revealed marked elevation of interferon (IFN) m¨, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-α were observed, while IFNm , IL-10 and sIL-2R were elevated initially during the HLH phase, which then decreased as LPD developed and B-cell proliferation predominated. Immunosuppressive chemotherapy for HLH may then have allowed latent EBV in B lymphocytes to induce transformation and oligoclonal proliferation of B-cells, finally resulting in LPD. Mechanisms of EBV-induced cell proliferation remain unclear, but alteration of various cytokines may be responsible for it.