High efficacy of combined rituximab and gemcitabine on Epstein-Barr virus-associated human B-cell lymphoma obtained after Hodgkin's xenograft in immunodeficient mice

The objectives were to characterize an Epstein-Barr virus-associated human B-cell lymphoma obtained from Hodgkin's xenograft, and to evaluate the in-vivo combination of rituximab and/or gemcitabine. A lymph node biopsy sample from a patient with Hodgkin's disease was xenografted into Rag gamma(-/-)(c) mice. Immunohistochemical, cytogenetic and genetic analyses were performed on both the human biopsy and xenografted tumor from severe combined immunodeficient mice. Tumor-bearing mice were then treated with rituximab and/or gemcitabine. Histologic features of the patient's biopsy concluded on classical CD15/CD30-positive Hodgkin's disease without expression of Epstein-Barr virus proteins. In contrast, morphologic and immunophenotypic examination of the xenograft showed diffuse proliferation of large B cells with high Epstein-Barr virus protein expression. Comparative genomic hybridization showed a normal pattern in the first case and a gain of chromosomal 12 in the xenografted tumor. Finally, polymerase chain reaction detected an immunoglobulin heavy chain rearrangement in the xenografted tumor. Altogether, these results indicate that the xenograft grew from the patient's Epstein-Barr virus-infected B-lymphoid cells and could be assimilated to posttransplant lymphoproliferative disease. In-vivo treatments of xenografted tumors showed significant tumor growth inhibition induced either by rituximab or gemcitabine alone and an impressive efficacy of combined treatment. This result therefore indicates that combined rituximab and gemcitabine could be an alternative approach in patients with posttransplant lymphoproliferative disease.