Aplastic anemia is a syndrome characterized by the decrease in hematopoietic stem cells along with bone marrow hypoplasia and pancytopenia, which is likely to be a T cell-mediated autoimmune disease. ...Since the response rate to immunosuppressive therapy is higher if started ahead of time, early initiation of treatment is recommended even in non-severe cases. Among treatment approaches in severe cases, immunosuppressive therapy with anti-thymocyte globulin (ATG) plus cyclosporin is the basic approach. However, the effectiveness of thrombopoietin receptor agonists has also been reported, with recovery of hematopoiesis in three blood lineages observed in some patients. Despite no evidence of increased incidence of genetic mutations with thrombopoietin receptor agonist treatment, bone marrow testing is recommended after three to six months of long-term treatment to detect the presence of chromosomal abnormalities. With regard to hematopoietic stem cell transplantation for aplastic anemia, cyclophosphamide is reduced as a pretreatment therapy, and instead, fludarabine is used in combination in order to reduce cardiotoxicity. Since HLA haploidentical hematopoietic stem cell transplantation has been developed and is being reportedly used in patients with no suitable donors, this transplantation approach might also be extended to aplastic anemia patients who were not considered eligible for transplantation in the past.
Interdigitating dendritic cell sarcoma (IDCS) is a rare and aggressive neoplasm that is thought to arise from dendritic cells. This disease usually involves the lymph nodes and, rarely, extra-nodal ...sites. We report a 62-year-old man presenting skin nodules in the head, body, and extremities, as well as bone marrow involvement. Morphologic analysis of a biopsied specimen from the skin lesion was consistent with IDCS. Immunohistochemical staining demonstrated that the tumor cells were positive for IDCS-associated antigens such as CD4, CD45, CD68 (KP-1), and S-100 protein. Complete remission was achieved by treatment with 6 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) chemotherapy. Although the optimal treatment of IDSC remains unknown, the experience in the current case supports the notion that ABVD chemotherapy may be effective for IDCS, and further extends this idea to rare patients presenting multiple skin lesions.
We conducted a retrospective analysis of patients younger than 60 years (N = 10, median age 54.5) with newly diagnosed primary central nervous system lymphoma (PCNSL) at the University of Tsukuba ...Hospital from January 2008 to November 2016. All the patients were scheduled to receive a single regimen without registration to any clinical trials. This was based on a phase 2 study by Memorial Sloan-Kettering Cancer Center (MSKCC); induction chemotherapy with rituximab, methotrexate, procarbazine, and vincristine (R-MPV) (five to seven cycles), followed by whole-brain radiotherapy (rd-WBRT) (23.4 Gy) and two high-dose cytarabine (HD-AC) cycles as a consolidation. The median age was 54.5 years, and median follow up duration was 33.1 months. The 3-year overall survival (OS) and progression-free survival (PFS) were 69% (95% CI 31–89%) and 56% (95% CI 20–81%). The median OS and PFS were not reached, respectively. Acute and delayed toxicities were manageable. In particular, OS and PFS of seven patients who achieved CR by the R-MPV induction chemotherapy were significantly superb (3-year OS, 100%; 3-year PFS, 80%), implying that a large proportion of patients in CR after the completion of this treatment may achieve durable disease control. On the other hand, all of the three patients who had progressive disease during this treatment died of disease progression within 1 year after diagnosis without achieving CR. Identifying the patients having a risk of failure in the R-MPV induction chemotherapy is important, and may allow us to consider a potentially more effective regimen.
Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A is the standard treatment for aplastic anemia (AA). The ATG formulation in Japan was changed from horse ATG ...Lymphoglobulin
®
(LG) to rabbit ATG Thymoglobulin
®
(TG) in 2009. Since then, 12 patients with AA have been treated with TG. Here, we summarize the effectiveness and safety of TG in comparison with data from 14 AA patients treated with LG before April 2009. One subject treated with LG but none treated with TG terminated the treatment due to a grade III adverse effect. The overall 6-month response rate after IST was similar for LG and TG (67 and 75 %). Infection was noted in five (38 %) and four (33 %) subjects treated with LG and TG, respectively. The initial response rate was significantly higher in the early-treatment group treated within a year of diagnosis than in the late-treatment group, who were treated more than a year after diagnosis (85 vs. 29 %, respectively), as reported previously, without apparent differences between the LG and TG groups. We conclude that TG at a dose of 2.5 mg/kg/day for 5 days is effective and safe in Japanese patients with AA.
Transcriptional regulation of animal genes has been classified into two major categories: tissue-specific and stress-inducible. Erythropoietin (EPO), an erythroid growth factor, plays a central role ...in the regulation of red blood cell production. In response to hypoxic and/or anemic stresses, Epo gene expression is markedly induced in kidney and liver; thus, the Epo gene has been used as a model for elucidating stress-inducible gene expression in animals. A key transcriptional regulator of the hypoxia response, hypoxia-inducible transcription factor (HIF), has been identified and cloned through studies on the Epo gene. Recently developed gene-modified mouse lines have proven to be a powerful means of exploring the regulatory mechanisms as well as the physiological significance of the tissue-specific and hypoxia-inducible expression of the Epo gene. In this chapter, several gene-modified mouse lines related to EPO and the EPO receptor are introduced, with emphasis placed on the examination of in vivo EPO activity, EPO function in nonhematopoietic tissues, EPO-producing cells in the kidney, and cis-acting regulatory elements for Epo gene expression. These in vivo studies of the Epo gene have allowed for a deeper understanding of transcriptional regulation operated in a tissue-specific and stress-inducible manner.
Erythropoietin (Epo) gene expression is under the control of hypoxia-inducible factor 1 (HIF-1), and is negatively regulated by GATA. Interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), which ...increase the binding activity of GATA and inhibit Epo promoter activity, are increased in patients with anemia of chronic disease (ACD). We previously demonstrated the ability of K-7174 (a GATA-specific inhibitor), when injected intraperitoneally, to improve Epo production that had been inhibited by IL-1β or TNF-α treatment. In the present study, we examined the ability of both K-11706, which inhibits GATA and enhances HIF-1 binding activity, and K-13144, which has no effect on GATA or HIF-1 binding activity, to improve Epo production following inhibition by IL-1β or TNF-α in Hep3B cells in vitro and in an in vivo mouse assay. Oral administration of K-11706 reversed the decreases in hemoglobin and serum Epo concentrations, reticulocyte counts, and numbers of erythroid colony-forming units (CFU-Es) induced by IL-1β or TNF-α. These results raise the possibility of using orally administered K-11706 for treating patients with ACD.
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