Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity

Supply of goods from hospitals to outpatients practicing intermittent self-catheterization in Japan

Hospitals supply goods to patients practicing intermittent self-catheterization (ISC), yet procedures for distribution have yet to be standardized, making it difficult to track the types of goods that are shipped and their amounts. The aim of this study was to standardize the types and amounts of goods provided by medical facilities on the basis of the survey results. We conducted a survey of medical facilities and patients regarding the status of goods supplied for ISC. Data were collected from January to May 2010 from 5 outpatient urology clinics and 26 patients practicing ISC. The first finding of this research is that the amount of supplied goods was insufficient and part of the supply method was incorrect. The second is that the status of goods supplied changed not only with ISC, but also with hospital characteristics. The third is that hospital costs averaged $63·10; the supplied catheter number affected hospital costs. Patient costs per month averaged$26·50, clearly showing that patients experience an economic burden. Patient costs were high in cases in which the percentage of types of goods supplied was low. A researcher analysed survey data to determine issues and procedures relevant to the supply of goods. The study showed a need to develop an optimal supply system for ISC patients and identified issues in the current system in Japan that require resolution. © 2012 The Authors. International Journal of Urological Nursing © 2012 BAUN & Blackwell Publishing Ltd

Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

Abstract4H-1-benzopyran-4-ones (chromones) are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E)-3-(4-hydroxystyryl)-6-methoxy-4H-chromen-4-one (compound 11), (E)-6-methoxy-3-(4-methoxystyryl)-4H-chromen-4-one (compound 4), (E)-6-methoxy-3-(3,4,5-trimethoxystyryl)-4H-chromen-4-one (compound 6) showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC) lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

Tumor-specificity and type of cell death induced by trihaloacetylazulenes in human tumor cell lines

The International Institute of Anticancer Researc

看護の現場で必要とされる言語についての調査と分析

看護現場ではさまざまなコミュニケーションが行われているが充分とはいえない。病院の看護師に英語と手話の必要性についてアンケートを実施し, 現場のニードを調査した結果を報告する。調査結果を元に看護英語の内容について考察し看護における言語教育のあり方を検討する

Japanese Science and Technology Indicators 2024

technical repor