Abstract
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) gamma, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-alpha were observed, while IFN gamma, 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.
Publication types
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Case Reports
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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B-Lymphocytes / pathology*
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B-Lymphocytes / virology
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Blotting, Southern
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Brain Neoplasms / etiology
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Brain Neoplasms / genetics
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Brain Neoplasms / virology
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Cell Division
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Cell Transformation, Viral
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Cyclophosphamide / adverse effects
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Cyclophosphamide / therapeutic use
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Doxorubicin / adverse effects
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Doxorubicin / analogs & derivatives
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Doxorubicin / therapeutic use
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Epstein-Barr Virus Infections / complications*
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Etoposide / adverse effects
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Etoposide / therapeutic use
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Fatal Outcome
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Herpesvirus 4, Human / isolation & purification*
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Herpesvirus 4, Human / pathogenicity
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Histiocytosis, Non-Langerhans-Cell / complications*
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Histiocytosis, Non-Langerhans-Cell / drug therapy
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Humans
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Immunosuppressive Agents / adverse effects*
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Immunosuppressive Agents / therapeutic use
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In Situ Hybridization
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Interferon-gamma / analysis
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Interleukin-10 / analysis
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Karyotyping
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Lymphocyte Activation
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Lymphoma, Large B-Cell, Diffuse / etiology*
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Lymphoma, Large B-Cell, Diffuse / genetics
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Lymphoma, Large B-Cell, Diffuse / virology
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Male
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Polymerase Chain Reaction
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Prednisolone / adverse effects
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Prednisolone / therapeutic use
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Receptors, Interleukin-2 / analysis
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T-Lymphocytes / pathology
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T-Lymphocytes / virology*
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Tumor Necrosis Factor-alpha / analysis
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Tumor Virus Infections / complications*
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Vincristine / adverse effects
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Vincristine / therapeutic use
Substances
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Immunosuppressive Agents
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Receptors, Interleukin-2
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Vincristine
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Etoposide
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Doxorubicin
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Interferon-gamma
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Cyclophosphamide
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Prednisolone