Improved outcome of acute lymphoblastic leukaemia treated by delayed intensification in Hong Kong children: HKALL 97 study

Objective. To study the outcome of children with acute lymphoblastic leukaemia who were treated using a protocol including one or two delayed intensifications. Design. Prospective single-arm multicentre study. Setting. Five designated children cancer units of the Hospital Authority of Hong Kong. Patients. Children aged between 1 and 17.9 years with newly diagnosed acute lymphoblastic leukaemia seen from November 1997 to December 2002. Intervention. Chemotherapy was modified from a German Berlin-Frankfurt-Muenster 95 (BFM95) protocol that included a delayed intensification similar to the induction phase repeated 5 months after diagnosis. High-risk patients were given double delayed intensification. Main outcome measures. Overall survival and event-free survival of the whole group and the three risk groups (standard-, intermediate-, and high-risk groups), and comparison with historical controls. Results. A total of 171 patients were recruited with a median age at diagnosis of 5.57 years (range, 1.15-17.85 years). The induction remission rate was 95.3% and non-leukaemia mortality during remission was 2.3%. At 4 years, the relapse rate of this (HKALL97) study was significantly lower than that of the HKALL93 study (15.7 vs 37.3%; P<0.001). The 4-year overall survival of HKALL97 and HKALL93 studies were 86.5% and 81.8%, respectively (P=0.51). The 4-year event-free survival for HKALL 97 and HKALL93 studies were 79% and 65%, respectively (P=0.007). Nonetheless the difference of event-free survival was most remarkable in the intermediate-risk group: 75.6% and 53.1% for HKALL97 and HKALL93 studies, respectively (P=0.06). Conclusion. A more intensive delayed consolidation phase improved the outcome for children with acute lymphoblastic leukaemia by reducing relapses at 4 years. The early treatment complications were manageable and non-leukaemia mortality during remission remained low.published_or_final_versio

Environmental and lifestyle risk factors of breast cancer in Malta-a retrospective case-control study

The funding for this research was obtained as part of IMaGenX – and ItaliaMalta co-financed EU project Operational Programme 2007–2013.AIM AND BACKGROUND: Environmental exposures are known to play a role in the development of cancer, including breast cancer. There are known associations of breast cancer with environmental factors such as sunlight exposure, diet and exercise and alcohol consumption as well as physiological factors. This study examines the prevalence of risk factors for breast cancer related to dietary intake, environment and lifestyle in the female population of Malta. Malta has had little research in this area, and therefore an exploratory study was carried out. METHODS: A retrospective case-control design was applied. Two hundred cases and 403 controls were included. Both cases and controls were subjects without a known family history for breast cancer. Controls were age-matched to cases in an age-decade category roughly at a 2:1 ratio. Interviews were carried out face-to-face using a questionnaire designed by Maltese and Sicilian researchers, encompassing various factors including diet, lifestyle, physiological factors and medical history. Breast cancer risk was then analysed using both univariate and multivariate analyses. For factors having a metric scale, the Mann-Whitney test was used to compare mean scores, while for categorical factors, the chi-square test was used to compare percentages between the case and control groups. Statistical modelling was carried out using binary logistic regression to relate the likelihood of breast cancer to over 50 risk/protective factors analysed collectively. RESULTS: Univariate analysis showed around 20 parameters of interest, 14 of which were statistically significant at a 0.05 level of significance. Logistic regression analysis identified 11 predictors of interest that were statistically significant. Tomato, coffee and canned meat consumption were associated with lower likelihood of breast cancer (OR = 0.988, 0.901, 0.892, respectively), whereas beans and cabbage consumption and low sodium salt were positively associated with breast cancer (OR = 1.045, 1.834, 1.028, respectively). Premenopausal status was associated with a lower risk of breast cancer compared to postmenopausal status (OR = 0.067). Not having experienced myocardial infarction was associated with lower odds of breast cancer (OR = 0.331). Increased height was also found to have a strong association with risk of breast cancer, with the odds of having breast cancer increasing for every centimetre increase in height (OR = 1.048). In terms of quantity, odds of having breast cancer were lower in those exposed to sunlight (OR = 0.891). The odds of having breast cancer were also lower in those not using the oral contraceptive pill (OR = 0.454). CONCLUSIONS: Various factors in this exploratory study were found to be associated with development of breast cancer. While causal conclusions cannot be made, tomato consumption is of particular interest, as these results corroborate findings found in other studies. A negative association of breast cancer with sunlight exposure and oral contraceptive pill use corroborates findings in other studies. Other associations with dietary intake can be explained by dietary changes. More robust studies in this area, including possible longitudinal studies, are warranted.peer-reviewe

Anti-inflammatory effects of high-dose montelukast in an animal model of acute asthma

Background Asthmatic inflammation is mediated by a network of cytokines, chemokines and adhesion molecules. Corticosteroids are the only effective agents available to control asthmatic inflammation. We investigated the effect of high-dose montelukast (MK), a selective cysteinyl leukotriene receptor 1 antagonist, on mediators of airway inflammation. Objective The aim of this study was to determine the effect of a 3-day course of high-dose MK on mediators of airway inflammation induced by a single allergen challenge in sensitized mice. Methods Ovalbumin (OVA)-sensitized BALB/c mice were treated with 25 mg/kg of MK or saline intravenously for 3 days. On the third day, a single inhalation challenge with OVA was given. Cellular infiltration was assessed in the bronchoalveolar lavage (BAL) and in the lung. Expression of IL-4, IL-5, IL-13 and eotaxin in the BAL, and the lung was determined. Serum IL-5 and total IgE was measured. IL-5 and eotaxin mRNA expression in the lung was determined. Finally, eotaxin and VACM-1 expression in the lung was assessed by immunohistochemistry. Results MK reduced the number of eosinophils in the BAL by > 90%. There was also significant reduction in IL-5 in the BAL, lung and the serum, and IL-5 mRNA expression in the lung. IL-4 level in the lung and BAL, and IL-13 level in the lung also significantly decreased. Serum IgE level and lung VCAM-1 expression was also significantly lower in treated animals, but eotaxin protein and mRNA expression in the lung remained unchanged. Conclusion MK exerts its anti-inflammatory effect through the suppression of T helper type-2 (Th2) cytokines. The use of high-dose MK as an anti-inflammatory agent in acute asthma should be further explored

A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong

A controlled, open-label and randomized study was conducted to evaluate the safety and efficacy of the oral iron chelator deferiprone (L1) in thalassemia major patients from Hong Kong. Forty-nine patients were recruited in total (median age: 20 years; range: 8 to 40 years). The division of the patients was determined based on liver iron content and put into either the poorly-chelated (Group I) or well-chelated (Group II) groups. In Group I, 20 patients received combined therapy of L1 daily plus desferrioxamine (DFO), in a reduced frequency of twice weekly, while the control group consisted of 16 patients who were treated with DFO alone. In Group II, six patients received L1 only, while the control group consisted of seven patients treated with DFO alone. Only patients who participated for longer than 6 months were analyzed for efficacy (n = 44). The median study period was 18 months. Transient and mild gastrointestinal upset (31%), joint pain (15%) and liver enzyme elevation (23%) were the most common side effects noted for L1. No case of neutropenia was observed in this study. Serum ferritin (SF) levels showed significant decline in the poorly-chelated patients using combined therapy (L1 and reduced frequency DFO) as compared to those on DFO alone. However, their pre- and post-study liver iron content was not significantly different. Evaluation of the well-chelated group demonstrated no significant change in SF or liver iron content in both the study and control arms. We conclude that the short-term use of L1, with or without DFO, was safe and efficacious in our Chinese patient cohort. The long-term efficacy of reducing iron overload by treatment regimens including L1 requires further study. Copyright © Taylor & Francis Group, LLC.link_to_subscribed_fulltextThe 15th ICOC Conference, 2005, Taichung, Taiwan, 22-26 Apr, 2005. In Hemoglobin, 2006, v. 30 n. 2, p. 263-27

Giant mediastinal lipoblastoma

A 3-year-old girl with fever, increasing cough, and nasal discharge for 2 weeks, was found to have a giant mediastinal lipoblastoma. The tumor weighing 556 g was successfully resected.link_to_subscribed_fulltex

Umbilical cord blood transplantation for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI)

Severe Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is usually fatal by early adulthood. Bone marrow transplantation is the only form of definitive enzyme replacement therapy available. A 5-year-old boy with Maroteaux-Lamy syndrome has successful recovery of bone marrow and enzymatic functions after umbilical cord blood transplant from his unaffected HLA-identical brother. Busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) were used as preparative chemotherapy with short methotrexate and long cyclosporin as prophylaxis against graft-versus-host disease (GVHD). A total of 6.08 x 10 7/kg nucleated cells and 2.92 x 10 5/kg CD34 + cells were transplanted with neutrophil engraftment achieved on day 26. There was no evidence of acute and chronic GVHD. Fifteen months after transplant, a normal level of N-acetylgalactosamine-4-sulphatase activity was achieved despite mixed chimerism. There was clinical improvement of hepatosplenomegaly, facial and skin features, joint mobility and resolution of suppurative middle ear effusion. He returned to school and continued to perform well in academic studies. We report here the first successful umbilical cord blood transplant as treatment of Maroteaux-Lamy syndrome.link_to_subscribed_fulltex