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EP-001. CENTRAL NERVOUS SYSTEM TUMORS IN CHINESE CHILDREN UNDER THE AGE OF THREE: A POPULATION STUDY BY THE HONG KONG PAEDIATRIC HAEMATOLOGY/ ONCOLOGY STUDY GROUP Anthony Pak-Yin Liu1, Matthew Ming-Kong Shing2, Hui-Leung Yuen3, Chak-Ho Li4, Siu-Cheung Ling5, Chung-Wing Luk3, Shau-Yin Ha1, Chi-Kong Li2, and Godfrey Chi-Fung Chan1; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong; Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Department of Paediatrics, Queen Elizabeth Hospital, Hong Kong, Hong Kong; Department of Paediatics and Adolescent Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong; Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, Hong Kong

Background Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. Procedure A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. Results This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. Conclusions The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

OBJECTIVES To review the clinical features, pathology and survivals of infants with brain tumours. METHODS A retrospective review of the clinical findings, pathology, treatment and survival outcome in infants with brain tumours. RESULTS From 1999 to 2018, there were 507 children ( CONCLUSION Infants with brain tumours have different pathology and inferior outcome.

METHOD: This clinical trial started from January 2008 and ended in June 2014. Patients who were suspected to have germinoma received a biopsy, followed by chemotherapy with carboplatin (600 mg per m(2) on day 1) and etoposide (150 mg per m(2) per day, day 1 to 3), alternating with ifosfamide (1.8 mg per m(2) per day and etoposide 150 mg per m(2) per day, day 1 to 5). They were assessed with MRI every 2 cycles. A total of 4 cycles of chemotherapy were given, followed by radiotherapy. The dose and volume of radiotherapy depend on the response and site of involvement. Patients with non-germinomatous germ cell tumours received operation to remove the tumour (if possible), chemotherapy as above for 6 cycles, reassessed by MRI once in two cycles, and cranio-spinal radiotherapy. The patients may need a second look operation if necessary. RESULTS: The data were reviewed on 31 May 2017. There were 45 patients, male to female ratio: 2.8:1, median age: 12.5 years of age (0.4 to 18.7). The pathology were germinoma (n=24) and non-germinomatous germ cell tumours (n=21). The locations of the tumours were suprasellar/sellar(n=13), pineal gland (n=20), suprasellar & pineal gland (n=7) and basal ganglia (n=4) and left frontal lobe (n=1). Five patients had metastatic diseases at presentation. Two patient had relapses. The median follow-up time was 6.75 years (2.43 to 9.54). PFS and OS at 5 years were 95.5% and 100% respectively. CONCLUSION: With a multi-disciplinary approach, a satisfactory outcome is achieved.

METHOD: Retrospective cohort for patients age 0 to 18 years old from January 1999 to Aug 2016 diagnosed to have low grade glioma. RESULT: Fifty-five patients diagnosed with pLGG with n=50 (91%) got a tissue diagnosis all showing astrocytoma WHO grade 1. Sites included cerebellum (n=29, 53%), cerebrum (n=10, 18%), brainstem (n=7, 13%), optic pathway (n=8, 15%) and spinal (n=1, 2%). Four patients (7%) have multi-focal tumours. Thirty-three (60%) patients received surgery alone and remained alive. Chemotherapy adopted including CCNU/CDDP/VCR, VCR/CPM/CDDP/VP-16, BLE/VP-16/CDDP, PCZ/CCNU/VCR, TMZ, CBDCA/VCR. Six (11%) received focal radiotherapy. One had NF-1 with thalamic lesion treated by surgery alone. One had TSC treated with mTOR inhibitor. Seven (13%) had progressive disease after chemotherapy and six remained alive. One had refractory brainstem tumour despite varies chemotherapy. The tumour had BRAF-KIAA1549 fusion and patient achieved stable disease after MEK-inhibitor (currently only 3 months). Three patients (5%) died. The first had parietal tumour at 12 years old received CCV and focal radiotherapy 54Gy, died from disease progression 5.8 years later. The second presented with diencephalic syndrome at 8 months old, received VCR/CPM/CDDP/VP-16 with stable disease, then died from status epilepticus 1.7 years later. The third had optic pathway glioma diagnosed at 2 months old, died from pneumonia 5.6 years from diagnosis. Median follow-up was 7.2 years (0.4-18). OS at 5 years was 94.1%. CONCLUSION: pLGG had excellent prognosis. Many patients treated successfully with surgery alone. New novel therapy from advanced molecular study might provide better prognosis and spare some patients from radiotherapy.

Background and aim We reviewed the results and pattern of failure of the consensus HB/HCC 1996 treatment protocol for pediatric hepatoblastoma (HB) in Hong Kong. The role of SIOPEL and Children's Hepatic tumors International Collaboration (CHIC) risk stratification was evaluated. Methods Patients enrolled on the protocol from 1996 to 2014 were included. PRETEXT staging, SIOPEL, and CHIC risk groups were retrospectively assigned. Results Sixty patients were enrolled with median age at diagnosis of 1.1 years and median follow-up time of 6.8 years. Alpha-fetoprotein (AFP) was raised (>100 ng/mL) in 58 (97%) patients. Five (8%) had metastases at presentation and 7 (12%) experienced tumor rupture prior to or during treatment. Twenty-nine patients (48%) received a first-line cisplatin, 5-fluorouracil, and vincristine regimen only while 23 (38%) also had alternative chemotherapeutic agents. Hepatic resection could be performed in 48 (80%) patients. Three (5%) patients underwent upfront liver transplantation. Five-year event-free survival and overall survival rates were 69.2% ± 6.1% and 77.6% ± 5.5% respectively. Among the 16 patients with relapse/progression, 9 had intrahepatic failure only, 5 had distant failure only, and 2 had combined local and distant failure. Predictors of inferior outcome included advanced Evans staging, disease involving both lobes, rupture, low AFP, and suboptimal response to first-line chemotherapy. Assigned in 44 patients, PRETEXT staging, SIOPEL, and CHIC risk groups significantly predicted EFS and OS. Conclusions Although the consensus HB/HCC 1996 protocol led to cure in three-quarters of pediatric HB patients, an upfront risk stratification system is required to identify and improve the outcome of high-risk patients.

Background Despite HIV being increasingly considered as a chronic illness, there is as yet no consensus about how primary care should be integrated with specialty care to provide optimal clinical management for people living with HIV. Objective To examine the effectiveness of shared care models of HIV between primary care and specialty care and how primary care providers can assist in improving the care of people with HIV. Methods Three databases, PubMed, Medline and EMBase, were searched for relevant terms from studies published in the period from 1996 to 2011. Studies that integrated primary care in HIV management and included highly active antiretroviral therapy (HAART) as part of the treatment modality were included. Results Eleven studies that met the inclusion criteria were included in this review. Primary care was found to be at least as effective in HIV counselling, testing and treatment and, to a lesser degree, prevention, when compared with specialty care alone. Screening for HIV at a primary care level was cost-effective, especially in a high HIV prevalence and high-risk community. There were no significant adverse clinical outcomes reported in a primary care approach. Effectiveness of various interventions using a primary care approach was demonstrated in the review, including HAART adherence programmes, home care, the involvement of peer health workers and perinatal use of HAART. Conclusions Primary care has an important role in the shared care of the diagnosis and management of people with HIV. Some improvements with current guidelines on the management in primary care of people with HIV in developing countries should be considered.

Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.

Hepatocellular carcinoma is a major health problem worldwide. Different treatment strategies have been developed to cope with this problem. Herbal medicine is now widely studied in both Eastern and Western countries. In this study, we used both in vitro and in vivo model to illustrate the anti-tumor effect of a product, CKBM, consisting of herbal medicine and specially processed Saccharomyces cerevisiae. Dose-dependent anti-proliferation effect was observed on in vitro growth of human hepatoma HepG2 cells after 48 hours incubation with CKBM. At the 50% inhibitory concentration (IC50) no significant toxic effect was observed on normal human fibroblasts Hs68 and human liver WRL-68 cells. The results of morphological changes, detection of DNA fragmentation, flow cytometric analysis and Western blot analysis indicated that this anti-tumor effect of CKBM was mediated via the process of apoptosis. In addition, HepG2 cells- bearing nude mice model was used for in vivo anti-tumor study. Our results showed that 14-day treatment with 0.8 ml daily dosage of CKBM could inhibit 54.1% of tumor growth. The plasma activities of enzymes specific for heart and liver, namely creatine kinase, lactate dehydrogenase, aspartate transaminase and alanine transaminase, remained at normal levels, indicated that CKBM did not produce toxicity to the host.

A population-based multicentre study for childhood acute lymphoblastic leukemia (ALL) was conducted in Hong Kong from 1993 to 1997. One hundred and forty-five newly diagnosed ALL patients were treated by the HKALL 93 protocol. Patients were stratified into three risk groups according to age, presenting white cell count, immunophenotyping and cytogenetic study. The patients received the same induction and early and late intensification at week 5 and week 20. Fifty-eight standard risk (SR) patients received regular intrathecal methotrexate as CNS preventive therapy, while 49 intermediate risk (IR) patients received high dose intravenous methotrexate and regular intrathecal methotrexate. Thirty-eight high risk (HR) patients were treated with prophylactic cranial irradiation and an additional intensification block at week 35. The induction remission rate was 97.2% with 2% induction death. Two patients died during first complete remission. Relapse occurred in 20.7, 42.9 and 42.1% of SR, IR and HR patients respectively. By multivariate logistic regression, age≥10 years and white cell count≥100×109/l were the two significant variables accounting for mortality. The 5-year overall and event-free survival of the whole group was 81.3 and 62.6% respectively. According to risk groups, the event-free survival was 79, 49 and 61% for SR, IR and HR patients respectively, while the overall survival was 96, 73 and 68% for SR, IR and HR patients respectively. In conclusion, the treatment protocol had low treatment-related mortality but was associated with a rather high relapse rate, especially in IR patients. Salvage therapy achieved sustained second remission in some patients. More intensive treatment especially a late intensification is required to improve the outcome. Copyright © 2002 John Wiley & Sons, Ltd.

To study the morbidity and mortality patterns of transfusion-dependent thalassaemia major patients in Hong Kong, and compare the outcomes of these patients according to different periods of birth.Retrospective study.Paediatric departments of three regional hospitals, Hong Kong.Medical records of thalassaemia major patients were reviewed. Data gathered included demographic and survival data, complications of iron overload, repeated transfusion, and bone marrow transplantation; the probability of survival of three cohorts was also estimated.Two hundred and thirty-two patients were studied at a median age of 15.5 years (range, 1.4-30.3 years). There were 60 patients born before 1980 (cohort 1), 117 patients born between 1980 and 1989 (cohort 2), and 55 patients born after 1989 (cohort 3). The median age of starting desferrioxamine was 8 years, 4 years, and 3 years for cohorts 1, 2, and 3, respectively. Cardiomyopathy, diabetes mellitus, and hypothyroidism occurred in 15.1%, 8.6%, and 6.9% of patients with thalassaemia major, respectively. The above complications developed in 5% to 12% of cohort 2 patients. Delayed puberty was present in 38.4% and hormonal replacement for gonadal failure was required in 29.7% of evaluable patients. Short stature was common and the median height standard deviation score was -1.63. Twenty patients had died, and cardiomyopathy was the leading cause of death, followed by complications of bone marrow transplantation. The probability of survival beyond the age of 20 years was 87.6%.Despite the use of iron chelation in the past two decades, severe complications of iron overload still occurred even in those who started chelation therapy early. Cardiomyopathy was the leading cause of death, while endocrinopathies and short stature were common complications especially in teenagers and adults.

Klebsiella infection has previously been reported in a few patients with transfusion-dependent thalassemia. The incidence and clinical spectrum of this infection in our cohort of patients were reviewed retrospectively. Among 160 patients observed for 12 years, there were 15 episodes of Klebsiella infection that occurred in 12 patients (7.5%), resulting in an incidence of 0.78 infections per 100 patient-years. The clinical spectrum included sinusitis (4 cases), intracranial infection (5 cases), septicemia (4 cases), and abscesses of the liver, lung, kidney, and parotid gland (1 case each). Three patients had recurrent infections involving different sites, 2 (16%) died of fulminant septicemia, and 3 (25%) had significant permanent neurological deficits. The antibiotic susceptibility pattern for the isolates was similar to the pattern for isolates recovered in the community. With regard to predisposing factors, iron overload and liver function derangement were found to be significant on univariate analysis ( and , respectively) but insignificant on multivariate analysis. Klebsiella infection P p .046 P p .049 was a serious and frequently encountered complication in our patients with transfusion-dependent thalassemia, resulting in high mortality and morbidity rates.