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Preemptive lamivudine in lymphoma patients undergoing intensive chemotherapy can effectively prevent chemotherapy-related HBV reactivation. Nevertheless, the safety profile after withdrawal of lamivudine and the impact of rituximab-containing chemotherapy on HBV reactivation has not been defined. To illustrate the necessity of prolonged surveillance after cessation of preemptive lamivudine in lymphoma patients treated with rituximab and chemotherapy, four patients with B-cell NHL carrying HBV received rituximab plus CHOP. Preemptive lamivudine therapy was administered 1 week before chemotherapy until 4 weeks after completion of chemotherapy. Serial serum alanine aminotransferase (ALT), total bilirubin, and HBV-DNA levels were prospectively monitored in three patients. The fourth patient was closely monitored for ALT. The HBV DNA was checked after development of clinical overt hepatitis. The peripheral blood CD20+ B-lymphocyte counts were analyzed periodically in two patients. All of the three patients studied prospectively had virological relapses with surgence of HBV DNA 6-8 months after completion of rituximab-plus-CHOP (R+CHOP) therapy. Two of the three patients had biochemical relapses and one of them developed severe hepatitis. Sequencing for HBV polymerase gene in these patients failed to show evident emergence of lamivudine-resistant mutations. The fourth patient developed a hepatitis flare-up 6 months after completion of chemotherapy. The CD2+ lymphocytes were totally depleted when HBV DNA started to increase. Delayed HBV reactivation can occur in lymphoma patients receiving R+CHOP after withdrawal of preemptive lamivudine. More protracted lamivudine therapy may be an alternative to close monitoring following chemotherapy, and further studies are needed to define optimal duration of lamivudine therapy.

To investigate the regulatory effects of decoy receptor 3 (DcR3) on the differentiation and function of dendritic cells (DCs), bone marrow-derived DCs (BM-DCs) from nonobese diabetic (NOD) mice were cultured with recombinant DcR3.Fc protein. Their differentiating phenotypes and T cell-stimulating functions were then evaluated. Expression of CD11c, CD40, CD54, and major histocompatibility complex I-Ag7 was reduced in cells cultured with additional DcR3.Fc, compared with DCs incubated with granulocyte macrophage-colony stimulating factor and interleukin (IL)-4, indicating that DcR3 interferes with the differentiation and maturation of BM-DCs. One of the most striking effects of DcR3.Fc on the differentiation of DCs was the up-regulation of CD86 and down-regulation of CD80, suggesting a modulatory potential to skew the T cell response toward the T helper cell type 2 (Th2) phenotype. Consistent with this, the proliferation of CD4+ T cells cocultured with DcR3.Fc-treated DCs was significantly reduced compared with that of T cells stimulated by normal DCs. Moreover, the secretion of interferon-γ from T cells cocultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating that DcR3 exerts a Th1-suppressing effect on differentiating DCs. Furthermore, adoptive transfer experiments revealed that NOD/severe combined immunodeficiency mice received DcR3.Fc-treated DCs, and subsequently, autoreactive T cells showed delayed onset of diabetes and a decrease in diabetic severity compared with mice that received normal DCs and T cells, suggesting a future therapeutic potential in autoimmune diabetes. Data from two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight analysis show an up-regulation of some proteins—such as mitogen-activated protein kinase p38 β, cyclin-dependent kinase 6, and signal-induced proliferation-associated gene 1—and a down-regulation of the IL-17 precursor; tumor necrosis factor-related apoptosis-inducing ligand family member-associated nuclear factor-κB activator-binding kinase 1; and Golgi S-nitroso-N-acetylpenicillamine in cells treated with DcR3, further demonstrating its effect on DC differentiation and function.