12例儿童AIDS患者特征分析

目的了解昆明儿童HIV／AIDS患者的流行特征、临床表现以及机会性感染发生部位及病原情况。方法对昆明市传染病医院自2001—2008年5月收治的12例儿童HIV／AIDS病人进行回顾性分析。结果母婴传播是本地区儿童HIV／AIDS最主要的传播途径（占100％）;发病年龄小（平均年龄2^7／14岁）,潜伏期短（平均潜伏期2-3年）。进展快;流行趋势减缓。最常见的临床表现为发热（75．0％）,精神萎靡（75％）,咳嗽（50％）,慢性腹泻（41．67％）,淋巴结肿大（41．67％）,皮肤病变（33．33％）,重度消瘦（8．33）。25％的患者白细胞总数低于正常,25％的患者血红蛋白低于9g/L,41．67％的患者血小板低于正常,胸片检查异常者占80％,CD4＋T细胞〈200cell／uL者占66．67％;机会性感染发生率为83.3％,最常见的机会性感染是：肺部感染（66．67％）,口腔真菌感染（41．7％）,皮肤感染（33．33％）,感染性腹泻（16．7％）,肺结核（16．7％）等。结论昆明儿童H1V／AIDS均经母婴传播,潜伏期短,流行趋势减缓。临床上以发热、精神萎靡、咳嗽、慢性腹泻及淋巴结肿大为常见症状,大多数病例胸片检查有异常,CD4＋T细胞下降。机会性感染表现为多系统,多种致病微生物并存,细菌、真菌、病毒均为常见病原,呼吸、消化系统以及皮肤软组织为常见感染部位。     

砷剂联合康力隆治疗MDS-RA

目的观察三氧化二砷（Arsenic trioxide ATO）联合康力隆治疗骨髓增生异常综合征（MDS）的临床疗效。方法25例原发性难治性贫血（MDS-RA）患者，其中男15例，女10例，中位年龄39．5岁。治疗方案为ATO10mg/d（儿童酌量），静脉点滴给药，连用30d，继以每月给药15d，总疗程4个月，同时服用康力隆4～6mg／d。结果基本缓解8例（32％），部分缓解5例（20％），进步或稳定者5例（20％），无效者7例（28％）。结论ATO联合康力隆治疗原发性MDS—RA是有效的，且副作用轻微，总有效率达72％，值得进一步应用总结。     

Identifying need in care homes for people with dementia: The relationship between two standard assessment tools

Considerable effort has been invested in improving assessment processes for older people, some of the most vulnerable of whom live in care homes. The paper compares two well-known assessment tools used in care homes, the CANE and the Minimum Data Set/Resident Assessment Instrument. There was poor agreement between the tools in terms of domains of need covered. Nineteen pairs of items could be compared, with agreement greater than 60% found on 11 items. Of the 15 items where κ could be computed, seven significant values were found. High levels of agreement existed in relation to behaviour, psychological wellbeing, mood state, psychotic symptoms, incontinence, mobility and inadvertent self-harm (risk). The study suggests that tools commonly used for assessment are not interchangeable and that the selection of assessment tool should be determined by the setting in which it is used, the needs of the population being assessed, the skills and knowledge of those undertaking the assessment and the purpose of the assessment itself.     

Phase II study of low-dose interleukin-11 in patients with myelodysplastic syndrome

Severe thrombocytopenia places patients with myelodysplastic syndrome (MDS) at risk of serious hemorrhage. Currently, therapeutic options are limited to platelet transfusions. The only commercially available growth factor that increases platelet counts is interleukin-11 (IL-11). We report the results of a phase II trial to more accurately assess the clinical response and toxicity data for low-dose IL-11 (10 μg/kg/day) in patients with MDS. In this study, nine of 32 assessable patients (28%) demonstrated increases in their platelet counts after treatment. Of these, five were considered major platelet responses (15%), as defined by World Health Organization criteria. Four patients had minor platelet responses (13%). The median duration of platelet response was 9 months. Low-dose IL-11 was well tolerated, with no observed grade 4 toxicities. Our study provides additional clinical evidence that chronic administration of IL-11, at low doses, can raise platelet counts and reduce platelet transfusion requirements in a subset of patients with MDS.     

Transplantation without pretransplant therapy: Is this a possibility? Insights into providing transplantation at diagnosis for patients with acute leukemia

Allogeneic hematopoietic stem cell transplantation (HSCT) has the potential for providing a cure for several hematologic malignancies. Although in most circumstances, allogeneic HSCT is preceded by disease-directed or cytoreductive therapy, it is unclear if these toxic conditioning regimens can be circumvented. This review summarizes evidence that will provide insights into factors that influence outcomes in allogeneic HSCT and whether this curative therapy could be used right at diagnosis.     

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1)

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report here a 20-year-old woman with severe transfusion-dependent anemia and reticulocytopenia. White blood cells and platelet counts were normal. Bone marrow examination showed a low percentage of erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis. A diagnosis of MDS (refractory anemia according to the FAB classification) with erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was confirmed by fluorescence in situ hybridization analysis. This translocation was detected in the apparently healthy younger brother, father, and aunt (father's sister) of the patient. Clonality of T cells in the patient was not confirmed by the polymerase chain reaction and heteroduplex temperature-gradient gel electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions known to be associated with erythroid hypoplasia, such as thymoma, were not present. The patient failed to respond to immunosuppressive therapy (antithymocyte globulin and cyclosporin A). Administration of recombinant human erythropoietin improved her anemia. To our knowledge, this balanced translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient with MDS with erythroid hypoplasia and in the healthy members of the family, has not been defined previously.     

Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

Current therapy of myelodysplastic syndromes

After being a neglected and poorly-understood disorder for many years, there has been a recent explosion of data regarding the complex pathogenesis of myelodysplastic syndromes (MDS). On the therapeutic front, the approval of azacitidine, decitabine, and lenalidomide in the last decade was a major breakthrough. Nonetheless, the responses to these agents are limited and most patients progress within 2 years. Allogeneic stem cell transplantation remains the only potentially curative therapy, but it is associated with significant toxicity and limited efficacy. Lack or loss of response after standard therapies is associated with dismal outcomes. Many unanswered questions remain regarding the optimal use of current therapies including patient selection, response prediction, therapy sequencing and combinations, and management of resistance. It is hoped that the improved understanding of the underpinnings of the complex mechanisms of pathogenesis will be translated into novel therapeutic approaches and better prognostic/predictive tools that would facilitate accurate risk-adaptive therapy.     

Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor

Introduction: HDAC inhibitors (HDACIs) have the potential to restore gene expression and display antitumor effects in vitro. As single agents, HDACIs have clinical activity in lymphoma. In myeloid leukemias, combinations of DNA methylation inhibitors and HDACIs are promising. Other combinations are being studied in solid tumors.

Areas covered: This article covers basic information and an update on preclinical and clinical experience with the oral isotype-selective HDACI MGCD0103 (mocetinostat) in hematological malignancies and solid tumors. It also examines data concerning MGCD0103 from recent conferences and articles through to November 2010, including new data regarding responses in lymphoma and toxicities.

Expert opinion: MGCD0103 is well-tolerated and exhibits favorable pharmacokinetic and pharmacodynamic profiles, demonstrating target inhibition and clinical responses. It induces cell death and autophagy, synergizes with proteasomal inhibitors and affects non-histone targets, such as microtubules. In 2008, new patient enrollment in trials was temporarily suspended due to potential cardiac complications. This restriction was lifted in 2009 as no correlation between MGCD0103 exposure and pericardial effusions was found. New patient enrollment in MGCD0103 clinical trials requires the exclusion of patients diagnosed with significant cardiac abnormalities prior to enrollment. Clinical and pharmacodynamic data support a three-times-weekly administration at a 90 mg fixed dose. MGCD0103 displays promising antitumor activity in several hematological diseases.