Se Ryeon Lee

Clinical significance of clonality and Epstein‐Barr virus infection in adult patients with hemophagocytic lymphohistiocytosis

We assessed the clinical significance of T or B cell clonality and Epstein-Barr virus (EBV) infection in adult patients with hemophagocytic lymphohistiocytosis (HLH) to identify factors related to prognosis. A total of 30 adult patients with diagnosed HLH were included in the study. In all patients, EBV-DNA in peripheral blood was examined by quantitative real-time polymerase chain reaction and bone marrow cells were examined for clonal rearrangement of T cell receptor gamma(TCRG) and immunoglobulin heavy chain (IGH) genes. TCRG clones were detected in 10 patients (33.3%) and IGH clones were detected in 8 patients (26.7%). We found no correlation between clonality and patient outcome. The patients less than 1,000 copies (mL)21 of EBVDNA showed a significantly higher clinical response (P 5 0.008) and longer overall survival (P 5 0.01) than those with high viral load of EBV-DNA. Our results suggest that TCRG and IGH rearrangement do not have any clinical significance in adult patients with HLH, but that high viral load of EBV-DNA may be a risk factor for poor outcomes. In HLH, high viral load of EBV-DNA should thus suggest a prompt approach with aggressive therapeutic interventions.

Bortezomib and melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma.

Background High-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT) is the standard treatment for young patients with multiple myeloma (MM). However, the response rates after ASCT are often unsatisfactory. We performed a pilot study by using bortezomib-melphalan as conditioning regimen for ASCT in Korean patients with MM. Methods The conditioning regimen consisted of administration of intravenous infusion of bortezomib 1.0 mg/m2 on days -4 and -1 and melphalan 50 mg/m2 (day -4) and 150 mg/m2 (day -1). In this study, we enrolled 6 newly diagnosed patients and 2 patients with relapse. Results The disease status of the 6 newly diagnosed patients at ASCT was as follows: 1 complete remission (CR), 1 very good partial remission (VGPR), and 4 partial remissions (PRs). The disease status of the 2 relapsed patients at ASCT was PR. All patients except 1 showed adequate hematologic recovery after ASCT. The median time for the absolute neutrophil counts to increase over 500/mm3 was 13 days (range, 10-19 days). Six patients with VGPR or PR at the time of transplantation showed an improvement in response to CR after ASCT. The patients were followed up without any maintenance treatment after ASCT except 1 patient who died during ASCT. During the follow-up period, CR was maintained in 3 newly diagnosed patients, but the other 4 patients, including 2 newly diagnosed patients, relapsed. Conclusion Conditioning regimen consisting of bortezomib and melphalan may be effective for ASCT in MM; however, the feasibility of this regimen should be further evaluated in large study populations.

Successful treatment of disseminated interdigitating dendritic cell sarcoma with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy

Interdigitating dendritic cell sarcoma (IDCS) is a very rare and aggressive neoplasm that arises from antigen presenting cells. IDCS usually involves lymph nodes; however, extra-nodal involvement has also been reported. Because a consistent standard therapy for IDCS has not been established to date, we report a case of the successful treatment of disseminated IDCS using ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). A 64-year-old man was diagnosed with IDCS on the basis of immunohistochemical findings of a biopsy specimen of the inferior nasal concha. Immunohistochemical staining showed a positive reaction for CD68, leukocyte common antigen, and S-100 protein, but a negative reaction for CD34, CD1a, and CD21. Imaging studies showed cervical and axillary lymphadenopathies, subcutaneous nodules, and a soft tissue lesion in the nasal cavity. Treatment with the ABVD regimen resulted in complete remission after 8 cycles of chemotherapy.

Successful control of steroid-intolerant Evans' syndrome associated with allogeneic peripheral blood hematopoietic stem cell transplant by rituximab

Immune-mediated cytopenias are relatively wellrecognized complications that occur after allogeneic stem cell transplant (allo-SCT). These can be associated with graft versus host disease (GVHD) and representative immune-mediated complications of allo-SCT, and can also be observed as isolated features. Recently, rituximab, a human–mouse chimeric monoclonal antibody specific for the CD20 antigen on the surface of B-lymphocytes, has been used in the treatment of chronic GVHD with/without autoimmune cytopenias in allo-SCT [1–4] and other immune-mediated hematologic diseases, such as Evans’ syndrome (ES) [5,6]. These clinical responses to rituximab have raised the possibility of a role for B-lymphocytes in the pathogenesis of these disorders. ES comprises rare, and hardly controllable, immune-mediated cytopenias that occur after alloSCT [7,8]. To date, no rituximab trials for the control of steroid-intolerant ES in this setting have been reported. Here, we demonstrate for the first time the effectiveness of rituximab for the treatment of steroid-intolerant ES after allo-SCT in a patient with acute myeloid leukemia (AML). A 17-year-old woman was referred to our department for an abnormal complete blood count (CBC), with white blood cell count (WBC) of 113.5610/mL with 95% immature cells. Bone marrow biopsy showed a finding of AML (French–American–British [FAB] M1) with a karyotype of 46,XX,del(9) (p22)[4]/46,XX[16]. Induction chemotherapy consisted of idarubicin and cytarabine (Ara-C), and the patient received two treatments of consolidation chemotherapy with a high dose of Ara-C. During the patient’s first complete remission (CR), allogeneic peripheral blood hematopoietic stem cell transplant (PBSCT) from an unrelated human leukocyte antigen (HLA)-matched, ABO mismatched (ABþ ! Aþ), and sex-mismatched donor was attempted. The conditioning regimen included 16 doses of busulfan (0.8 mg/kg IV every 6 h), six doses of fludarabine (30 mg/m/day), and three doses of rabbit antithymocyte globulin (Thymoglobulin; SangStat, Lyon, France and Genzyme Corp., Cambridge, MA, USA) (3 mg/kg/day). Prophylaxis against GVHD consisted of tacrolimus and methotrexate. Plasmapheresis was performed for the prevention of immune hemolysis. Hematologic reconstitution was acquired approximately 1 month later; 99.7% of bone marrow cells were 46,XY with fluorescence in situ hybridization, compatible with complete engraftment. Polmerase chain reactionpolyacrylamide gel electrophoresis (PCR-PAGE) showed no residual recipient cells in the bone marrow. No acute GVHD was observed. Tacrolimus was maintained for the prevention of chronic GVHD. On day 118 after transplant, anemia and thrombocytopenia were observed (hemoglobin [Hb] 11.6 g/dL, WBC 5.3610/mL, platelets 103610/mL), and the patient’s bone marrow was examined on day 127. Bone marrow aspirates showed hypocellular (for her age) marrow particles, without residual leukemic

Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells ☆

ETHNOPHARMACOLOGICAL RELEVANCEnUlmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis.nnnMATERIALS AND METHODSnCytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells.nnnRESULTSnUDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death.nnnCONCLUSIONSnFrom our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.