Paediatric high-grade osteosarcoma and its prognostic factors: a 10-year retrospective study.

INTRODUCTION: This retrospective study was conducted to identify the characteristics of paediatric high-grade osteosarcoma and define its prognostic factors. METHODS: We identified paediatric patients (aged <19 years at diagnosis) diagnosed with high-grade osteosarcoma from 1 January 2009 to 31 December 2018 in two hospitals in Hong Kong, then retrospectively evaluated their medical records to identify prognostic factors. RESULTS: In total, 52 patients were included in this study (22 girls, 42.3%). Femoral tumour was the most common form of osteosarcoma. Most patients (78.8%) had localised disease at diagnosis. The lung was the most common site of metastasis. Almost half (n=23, 46.9%) of the patients showed a good response to chemotherapy (ie, chemonecrosis >90%). Most patients (n=40, 80%) underwent limb-salvage surgery. The event-free survival and overall survival rates were 55.8% and 71.2%, respectively. Prognostic factors independently associated with poor event-free survival and poor overall survival were the presence of metastasis at diagnosis, poor tumour chemonecrosis, and the need for amputation. CONCLUSION: This multicentre review of paediatric high-grade osteosarcoma showed that the baseline patient demographics, event-free survival, and overall survival in Hong Kong were similar to previous findings in other countries. Patients with metastatic disease at diagnosis and poor chemonecrosis had worse survival outcomes. Molecular analyses of genetic abnormalities may help to identify targeted therapies in future studies.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Treatment outcome and pattern of failure in hepatoblastoma treated with a consensus protocol in Hong Kong.

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.

Outcomes and morbidities of patients who survive haemoglobin Bart's hydrops fetalis syndrome: 20-year retrospective review.

INTRODUCTION: Haemoglobin Bart's hydrops fetalis syndrome was once considered a fatal condition. However, advances over the past two decades have enabled survival of affected patients. Data relating to their morbidities and outcomes will help medical specialists formulate a management plan and parental counselling. METHODS: All babies with the syndrome who survived beyond the neonatal period and were subsequently managed long-term in eight public hospitals in Hong Kong from 1 January 1996 to 31 December 2015 were included. Patient and parent characteristics, antenatal care, reasons for continuation of pregnancy, intrauterine interventions, perinatal course, presence of congenital malformations, stem-cell transplantation details, and long-term neurodevelopmental outcomes were reviewed. RESULTS: A total of nine patients were identified, of whom five were female and four male. The median follow-up duration was 7 years. All were Chinese and were homozygous for the Southeast Asian α-thalassaemia deletion. Five of the nine mothers received antenatal care at a public hospital and opted to continue the pregnancy after antenatal diagnosis and counselling. Despite intrauterine transfusions, all babies were born with respiratory depression and required intubation and mechanical ventilation during the neonatal period. Hypospadias was identified in all four male infants. Growth retardation, global developmental delay, and residual neurological deficits were noted in two-thirds of the patients. Haematopoietic stem-cell transplantation was performed in two patients, who became transfusion-independent. CONCLUSIONS: Survival of patients with Bart's hydrops fetalis syndrome is possible but not without short- and long-term complications; local epidemiology is comparable to that documented for an international registry. Detailed antenatal counselling of parents with a non-judgemental attitude and cautious optimism are imperative.

Spatiotemporal variation of ozone precursors and ozone formation in Hong Kong: Grid field measurement and modelling study.

Grid field measurements of volatile organic compounds (VOCs) covering the entire territory of Hong Kong were simultaneously carried out twice daily on 27 September 2013 and 24 September 2014, respectively, to advance our understanding on the spatiotemporal variations of VOCs and ozone (O3) formation, the factors controlling O3 formation and the efficacy of a control measure in Hong Kong. From before to after the control measure on liquefied petroleum gas (LPG) fueled vehicles, the VOCs originated from LPG vehicle exhaust deceased from 41.3±1.2µg/m(3) (49.7±1.5%) to 32.8±1.4µg/m(3) (38.8±1.7%) (p<0.05). In contrast, the contribution to VOCs made by gasoline and diesel vehicle exhaust and solvent usage increased (p<0.05). VOCs and nitric oxide (NO) in LPG source experienced the highest reductions at the roadside sites, while the variations were not significant at the urban and new town sites (p>0.05). For O3 production, LPG vehicle exhaust generally made a negative contribution (-0.17±0.06 ppbv) at the roadside sites, however it turned to a slightly positive contribution (0.004±0.038 ppbv) after the control measure. At the urban sites, although the reductions of VOCs and NO were minor (p>0.05), O3 produced by LPG vehicle significantly reduced from 4.19±1.92 ppbv to 0.95±0.38 ppbv (p<0.05). Meanwhile, O3 produced by LPG at the new town sites remained stable. The analysis of O3-precursor relationships revealed that alkenes and aromatics were the main species limiting roadside O3 formation, while aromatics were the most predominant controlling factor at urban and new town sites. In contrast, isoprene and sometimes NOx limited the O3 formation in rural environment.

Is there a role for primary care clinicians in providing shared care in HIV treatment? A systematic literature review.

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.

Klebsiella infection in patients with thalassemia.

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 (P=.046 and P=.049, respectively) but insignificant on multivariate analysis. Klebsiella infection was a serious and frequently encountered complication in our patients with transfusion-dependent thalassemia, resulting in high mortality and morbidity rates.

Treatment of acute lymphoblastic leukemia in Hong Kong children: HKALL 93 study.

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> or =10 years and white cell count> or =100 x 10(9)/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.

Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study.

OBJECTIVES: 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. DESIGN: Retrospective study. SETTING: Paediatric departments of three regional hospitals, Hong Kong. SUBJECTS AND METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Successful mismatched sibling cord blood transplant in Hb Bart's disease.

A 20-month-old girl with Hb Bart's disease, who had survived neonatal complications, underwent HLA-DR antigen mismatched sibling cord blood transplantation successfully. Immune thrombocytopenia, which occurred around 2.5 months after transplant, responded to intravenous gamma-globulin. The fetal hemoglobin level rose to a peak of 52.3% on day +69 post transplant and declined gradually during the following year. Ten percent of hemoglobin Bart's was detected 2 months after transplant and this reflects the alpha-thalassemia trait of the donor.