Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial.

PURPOSE: We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL. PATIENTS AND METHODS: A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT. RESULTS: Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3. CONCLUSION: Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.     

Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: are there molecular markers in the primary tumour that predict for 5-year clinical outcome?

BACKGROUND: Locally advanced and/or inflammatory breast cancer (LABC) is a heterogeneous disease. Molecular markers may help to understand this heterogeneity. This paper reports the results of a study assessing the potential prognostic or predictive value of HER-2, p53, cyclinD1, MIB1, ER and PgR expression by immunohistochemistry from patients included in an EORTC-NCIC-SAKK trial. PATIENTS AND METHODS: A total of 448 patients with a cytological or histological diagnosis of LABC were randomised into a trial comparing two anthracycline-based neoadjuvant regimens. Chemotherapy was followed by standard locoregional therapy. Survival was comparable in both arms. We collected and analysed centrally paraffin-embedded tumour specimens from 187 (72.5%) of 258 patients that had a histological diagnosis. RESULTS: Of the patients included in this molecular marker study 114 relapsed and 91 died. In the multivariate analysis p53 positivity was associated with a shorter progression-free survival [hazard ratio (HR) = 1.96; 95% CI 1.33-2.91; P = 0.0008) and a shorter overall survival (HR = 1.98; 95% CI 1.28-3.06; P = 0.002). PgR positivity predicted for a longer overall survival (HR = 0.54; 95% CI 0.35-0.83; P = 0.0045). CONCLUSIONS: p53 was an independent factor predicting for survival. In order to clarify whether p53 is a pure prognostic and/or a predictive factor, a phase III trial is being conducted (EORTC 10994/BIG 00-01 study) using functional assay in yeast from frozen tumour samples.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Thrombopoietic factors potentially useful in the treatment of acute leukemia

Thrombocytopenia is a major cause of morbidity following intensive chemotherapy for acute leukemia. Over recent years, there has been an increasing use of platelet transfusions which, although generally efficacious to prevent severe hemorrhage, have associated risks of transmitting blood-borne disease and of alloimmunization. Therefore, there is a clinical requirement for a drug that will reliably alleviate the thrombocytopenia associated with leukemia therapy. The c-mpl ligand thrombopoietin is the most interesting factor for the treatment of thrombocytopenia because of its lineage specificity. Phase I and II studies confirm its biological efficacy to induce rise in platelet count in patients with solid tumors and acute leukemia. Several other pleiotropic hematopoietic growth factors are also currently in clinical trials. These include interleukin-6, interleukin-3, interleukin-11, PIXY321 and stem cell factor. The effects of these cytokines appear to be modest at most and, with the exception of interleukin-11, their side effects are likely to limit their clinical application. Combinations of factors may prove more efficacious approaches to enhance platelet recovery.     

肾上腺Cushing综合征病因学上的进展

由中华医学会内分泌学分会主办，国际内分泌学会参加的2006年内分泌代谢性疾病系列研讨会——全脚内分泌肿瘤基础和临床研究专题研讨会，于7月7～9日在西南省昆明市举办。此次大会是中华医学会内分泌学分会与国际内分泌学会首次联合举办的大会。国际内分泌学会山执行委员，负责学术会议的主席、肾上腺疾病研究方面的专家法国Xavier Bertagna教授带队，由国际内分泌学会邀请了分别在神经内分泌和甲状腺疾病领域深有研究的著名专家英旧Ashley Grossman教授和美国James A Fagha教授，……     

Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.
Methods: The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).
Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima–media thickening greater than 1.2 mm.
Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.     

Family burden and coping strategies in schizophrenia: 1-year follow-up data from the BIOMED I study

Background: To date, only few data are available on how family burden in schizophrenia changes over time. In addition, no study has explored how such factors as coping styles and social support influence burden over time. This paper presents the 1-year follow-up data from the BIOMED I study on family burden and coping strategies in schizophrenia. Methods: A sample of 159 relatives of patients with schizophrenia living in five European countries was followed up prospectively for 1 year with regard to burden and coping strategies, using validated questionnaires. Results: In the sample as a whole, the burden was stable. A reduction of family burden over time was found among relatives who adopted less emotion-focused coping strategies and received more practical support from their social network. In addition, family burden decreased in relation to the improvement of patient's social functioning. Conclusions: When relatives of patients with schizophrenia are able to improve their coping strategies, it is possible for burden to be reduced even after several years. This points to the necessity to provide families of chronic psychotic patients with psychoeducational interventions emphasising the adoption of an effective coping style. Accepted: 22 November 1999     

Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.