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We have developed a method that cells exhibiting typical dendritic cell (DC) characteristics are generated from human CD34(+) cells and phagocytose cogenerating erythroid progenitor cells in the presence of tumor necrosis factor-alpha (TNF-alpha), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF antagonists, etanercept and infliximab, on TNF-alpha activity. We found that 1 microg/ml etanercept dramatically inhibited the generation of CD11c(+) cells accompanying with a complete recovery of the generation of erythroid progenitors. Infliximab at 200 microg/ml exhibited a similar effect to that observed for etanercept. The delayed addition of etanercept to this culture system at day five resulted in significant inhibitory effects on the generation of CD11c(+), CD4(+) and CD86(+) cells. These results indicate that TNF antagonists administered at a concentration that is achievable in vivo, neutralize the biologic effects of TNF-alpha in generating CD11c(+) cells and that a delay in the administration of these antagonists for as long as 5 days partially inhibits the biologic activity of TNF-alpha. These findings may contribute to a great understanding of anti-TNF therapy in patients with an overproduction of cytokines such as hemophagocytic syndromes. [ABSTRACT FROM AUTHOR]

A 79-year-old male patient presented with systemic lymphadenopathy. A lymph node biopsy revealed effacement of the normal nodal architecture with diffuse proliferation of medium-sized atypical lymphoid cells. Southern blot analyses demonstrated rearrangement of the T-cell receptor gene but not the immunoglobulin heavy chain gene. He was diagnosed with CD20-positive peripheral T-cell lymphoma (PTCL), NOS. Although he achieved partial remission after six cycles of R-CHOP, he relapse occurred after 2 months. CD20-negative conversion was confirmed in the lymph node, which was positive for CCR4, and the skin at the time of relapse. The patient received the GDP regimen as salvage therapy with the addition of vorinostat for skin involvement; however, he failed to respond, and the disease systemically progressed. Furthermore, he also exhibited progression in the skin after stopping vorinostat due to hematologic toxicity. A lymph node biopsy at progression revealed CD20 re-expression by immunohistochemistry. At progression, the patient received mogamulizumab but failed to respond, and he died owing to disease progression 8 months after relapse. In this case, we demonstrated CD20-negative conversion following rituximab and CD20-positive reversion after using vorinostat and gemcitabine.

A 58-year-old woman was admitted to our hospital for evaluation of left flank pain. Abdominal computed tomography showed a greatly enlarged splenic tumor with a massive portal vein tumor thrombosis (PVTT). We suspected non-Hodgkin lymphoma (NHL) based on the high values of serum soluble interleukin-2 receptor and lactate dehydrogenase. Because there was no superficial lymph node enlargement, ultrasound-guided percutaneous trans-hepatic needle biopsy was performed to obtain a pathological diagnosis of PVTT, instead of a splenectomy, after the patient had provided informed consent. This procedure was thought to be less invasive than splenectomy. Histologic examination revealed CD20-positive NHL. A complete response was achieved after six courses of R-CHOP and it was confirmed by splenectomy. A PVTT due to NHL is extremely rare as compared with that due to hepatocellular carcinoma, gastric cancer, and colon cancer. However, NHL should be considered in the differential diagnosis for a patient with a PVTT, because B cell-NHL tends to have a good prognosis when rituximab combined chemotherapy is administered. We suggest that a percutaneous trans-hepatic needle biopsy may be useful for diagnosing PVTT due to NHL.