[Show abstract][Hide abstract] ABSTRACT: Background:
Renal tumors are one of the most common tumors in children. We aim at evaluating the characteristics and the outcome of Wilms tumor and other malignant kidney tumors in Hong Kong.
Between January 1990 to December 2010, 68 patients under the age of 18 with malignant renal tumors were diagnosed and received treatment in Hong Kong. Clinical records were updated regularly. Prognostic factors and survival rate were evaluated.
Fifty-four patients were diagnosed with Wilms tumor. The annual incidence was estimated to be 2.29 per million. The mean age was 38 months. Median follow-up was 9.2 years. The event-free survival and overall survival rate at 10 years were 85.2% and 92.6%, respectively. A pair of siblings with familial extrarenal Wilms tumor was included. Pulmonary metastasis did exhibit a significant difference in survival rate. Eight cases of clear cell sarcoma of the kidneys were reported and the survival rate was 100%.
The clinical characteristics and outcome of the patients diagnosed Wilms tumor were comparable with other developed countries. Relatively high proportion and excellent outcome were found in clear cell sarcoma of the kidneys.
No preview · Article · Aug 2014 · Journal of Pediatric Hematology/Oncology
[Show abstract][Hide abstract] ABSTRACT: The management of CNS tumors in children below the age of three represents special challenge to pediatric oncologists with
distinctive epidemiology, treatment considerations and prognosis. Population-based epidemiological data on this particular
patient group is lacking in Chinese. We reviewed the population-based pediatric tumor registry of the Hong Kong Paediatric
Haematology/Oncology Study Group between 1999 and 2011. Eighty-one children with primary CNS tumors from 0-3 years were identified
(annual incidence: 4.16 cases per 100,000). Forty-one (50.6%) were male and mean duration of FU was 94 months (±8.1). Primary
tumors were infratentorial in 43 (53.1%). The tumor types in decreasing frequency were astrocytoma (n = 17), medulloblastoma
(n = 16), ependymoma (n = 13), CPT (n = 7), PNET (n = 7), ATRT (n = 6), GCT (n = 5), craniopharyngioma (n = 4) and ganglioglioma
(n = 3). Three patients presented antenatally. Treatment included surgery in 82.7%, chemotherapy in 50.6% and radiotherapy
in 25.9%. There were 29 deaths (35.8%) and 19 relapses (23.5%) during the review period with the 1y-OS, 5y-OS, 1y-EFS and
5y-EFS being 79.4% (±4.6), 63.5% (±5.9), 68.9% (±5.3) and 52.5% (±5.9) respectively. Significantly better OS and EFS were
observed in patients who received gross-total resection but those with high-grade tumors, antenatal diagnosis or ATRT/PNET
had worse outcome. Survival did not differ with age. Comparison with statistics from other studies revealed higher rates of
embryonal tumor, GCT and craniopharyngioma in Hong Kong Chinese. Disease outcome appeared to be better in our cohort comparing
to previous reports probably due to the higher proportion of GCT locally.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The purpose of this study is to determine the burden of the peak severity of oral mucositis and severity over time on selected clinical outcomes in paediatric and adolescent patients receiving chemotherapy.
Patients and methods:
A multicentre study enrolled 140 patients between the ages of 6 and 18 years, who had been treated with chemotherapy and completed the self-report Mouth and Throat Soreness-related questions of the Oral Mucositis Daily Questionnaire for 14 days. Clinical data were collected from patients' medical records during the first 14 days after starting chemotherapy.
Forty-one percent developed oral mucositis. Multiple linear regression analysis revealed that oral mucositis was significantly associated with an increased loss of baseline body weight, after controlling for nausea/vomiting (β = 0.34, p = 0.002). Multiple logistic regression analysis showed that severe mucositis was significantly associated with a higher probability of fluid replacement, after controlling for nausea/vomiting (adjusted OR = 12.8; 95 % CI = 2.7-61.0; p = 0.001). In addition, severe mucositis was significantly associated with a higher probability of fever, after controlling for neutropoenia (adjusted OR = 5.4; 95 % CI = 1.8-15.4; p = 0.002). No difference was observed for oral or systemic infections among the subgroups. About 5 % of the patients with oral mucositis had delays in chemotherapy (≤ 7 days). None of the patients had dose modification or unplanned hospitalization due to oral mucositis. The associations of peak severity and overall oral mucositis with adverse clinical outcomes in paediatric and adolescent patients were equivalent.
Oral mucositis is associated with negative effects on clinical outcomes.
No preview · Article · Mar 2013 · Supportive Care in Cancer
[Show abstract][Hide abstract] ABSTRACT: Haemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. We report a onemonth- old infant presented with fever, pancytopenia, liver derangement, coagulopathy, and was subsequently diagnosed to have HLH. No secondary cause could be identified after extensive workup. She developed multi-organ failure with severe lactic acidosis that was refractory to other treatment. Continuous renal replacement therapy successfully corrected her lactic acidosis. Our case highlights the importance of monitoring serum lactate level in critically ill patients with severe metabolic acidosis.
No preview · Article · Jul 2012 · Hong Kong Journal of Paediatrics
[Show abstract][Hide abstract] ABSTRACT: Between May 2002 and August 2010, a total of 38 patients, who were clinically diagnosed as, but without surgical biopsy confirmation,
intracranial germ cell tumors (GCTs) were treated at our Cancer Center. The patients were grouped into chemotherapy(n = 21
), radiotherapy(n = 5), and stereotactic radiotherapy (n = 12) based on the primary treatment. Median age of the patients
at diagnosis was 16 years old with 33 males and 5 females. There were 68.4% (26/38) patients had elevatedβ-HCG and/or AFP
in serum, cerebrospinal fluid, or both. In which, 12 patients had received prior ventriculo- peritoneal shunt. Twenty-one
patients received primary chemotherapy, in which 17 patients followed by adjuvant radiotherapy. There were 9 complete responses
(CR), 8 partial responses (PR), 2 stable diseases (SD) and 2 not evaluated (NA). The objective response rate (ORR) was 81%.
Five patients received primary radiotherapy, 1 of which followed by adjuvant chemotherapy. There were 3 CR and 2 PR, the ORR
was 100%. Twelve patients received primary stereotactic radiotherapy (SRS), in which, 4 patients followed by adjuvant chemotherapy,
8 patients received salvage chemotherapy when disease recurred. Six of 12 patients received whole brain or craniospinal radiotherapy
after chemotherapy. There were 2 CR, 9 PR and 1 SD, and the ORR was 91.7%. Chemotherapy consisted of cisplatin, VP-16/VM-26
and bleomycin (PEB regimen). With a median follow-up of 29 months, 23 patients (60.5%) are alive without evidence of disease,
while 6 patients died of tumor progression. The 2-year overall survival rate(OS) of total group was 79.5%. The 2-year OS of
patients with primary chemotherapy, radiotherapy, and SRS was 89.1%, 66.7% and 90%, respectively (p = 0.51). CONCLUSIONS: Chemotherapy and/or radiotherapy were highly effective in the patients with histologically unconfirmed
intracranial GCTs. The optimal treatment for intracranial GCTs is worth further investigation.
[Show abstract][Hide abstract] ABSTRACT: Primary Leptomeningeal Anaplastic Oligodendroglioma (PLAO) is a very rare tumor that grows in the subarachnoid space with
no obvious findings of intraparenchymal mass lesion. Here we report an 11-year-old girl who was diagnosed as PLAO with temporal
bone invasion. She has a history of shunted hydrocephalus of unknown etiology since the age of 8. Computed tomography (CT)
scan had showed bifrontal subdural hygroma without intracranial or extracranial mass lesion until she developed right exophthalmos
at the age of 11. CT scan and magnetic resonance imaging (MRI) revealed temporal bone tumor extending right orbital bone and
diffuse leptomeningeal thickening. The biopsy was performed and histopathology revealed anaplastic oligodendroglioma. Combination
chemotherapy with CDDP, CY and VP16 was started, and decreased the size of the tumor and improved her exophthalmos. After
5 cycles of the chemotherapy, TMZ was given for maintenance therapy. However, she developed leg paralysis and urinary incontinence
6 months later due to the worsening of leptomeningeal thickening throughout the spinal canal and intracranial space. Whole
brain/spine radiotherapy was given, which decreased the tumor size and improved her neurological symptoms. A few months after
cessation of chemotherapy, subcutaneous tumor was noted along the scar of LP shunt catheter. The subcutaneous tumor was surgically
resected. Histopathology showed anaplastic oligodendroglioma and G-banding analysis showed the presence of i(1)(q10). Bone
marrow metastasis was also noted at this time. Chemotherapy using IFO, CBDCA and VP16 was restarted. In response to treatment,
serum LDH increased to 6.000 and then returned to normal. Tumor cells in the bone marrow almost disappeared after one cycle
of chemotherapy. She has been stable without recurrence of the tumor for three months since then. PLAO is relatively slowly
progressive and treatment using multiple modalities seems to be effective for this tumor.
[Show abstract][Hide abstract] ABSTRACT: Four patients (age 3-11 years at diagnosis) with relapsed acute promyelocytic leukemia (APL), 12-38 months from diagnosis, were treated with oral arsenic trioxide (As(2) O(3) ). One patient was treated with oral As(2) O(3) monotherapy and chemotherapy. Three patients failed initial oral or intravenous As(2) O(3) monotherapy were treated with oral As(2) O(3) plus ATRA followed by long-term oral maintenance (cumulative As(2) O(3) dose 280-2,100 mg). All patients achieved molecular remission, at a median follow up of 122 (10-132) months with no adverse effects. Oral As(2) O(3) , particularly in prolonged maintenance with oral ATRA may obviate the need of stem cell transplantation in relapsed pediatric APL.
No preview · Article · Apr 2012 · Pediatric Blood & Cancer
[Show abstract][Hide abstract] ABSTRACT: This study sought to characterize the range of oral symptoms and affect upon quality of life reported by pediatric and adolescent patients in relation to the severity of oral mucositis and symptom burden during chemotherapy.
A multicenter study included 140 patients between 6 and 18 years of age who had been treated with chemotherapy. Participants completed the self-report Mouth and Throat Soreness-related Questions of the Oral Mucositis Daily Questionnaire (OMDQ) for 14 days and the Oral Mucositis-specific Quality of Life Measure (OMQoL) at baseline, day 7, and day 14.
The incidences of non-severe and severe mucositis were 23% (n = 32) and 18% (n = 25), respectively. The symptoms reported by the patients with oral mucositis were related to eating (82.4%), swallowing (78.9%), drinking (75.4%), sleeping (71.9%), and talking (43.9%). Approximately 39% (22 out of 57) of patients with mucositis reported at least two simultaneous symptoms resulting from oral mucositis. About a quarter of them (25%, 14 out of 57) reported having all five symptoms concurrently. The mean area under curve (AUC) scores for symptom severity were significantly higher in the severe mucositis group (mean 0.95 to 1.21; 95% CI 0.76 to 1.34) compared with the non-severe (mean 0.50 to 1.06; 95% CI 0.35 to 1.30) and the without mucositis (mean 0 to 0.09; 95% CI 0 to 0.12) groups (p < 0.001). Wald's method generated two clusters: a low-symptom group (n = 102; 72.9%) and a high-symptom group (n = 38; 27.1%). The high-symptom group reported significantly lower mean AUC OMQoL subscale scores (mean 62.2 to 79.2; 95% CI 55.9 to 88.2 versus mean 93.1 to 97.1; 95% CI 91.7 to 98.3, respectively; p < 0.001) and higher mean AUC distress score (mean 1.9 ± 0.5; 95% CI 1.7 to 2 versus mean 1.1 ± 0.2; 95% CI 1.1 to 1.1, respectively; p < 0.001) than the low-symptom group. Swallowing and sleeping had the strongest standardized coefficients in OMQoL subscale scores (swallowing: -0.321 to -0.767; sleeping: -0.406 to -0.773), as well as distress scores (0.468 and 0.557, respectively).
Severe oral mucositis is a common cause of morbidity in pediatric and adolescent patients undergoing chemotherapy. High-symptom burden due to mucositis may have profound impacts on patient quality of life and levels of psychological distress.
No preview · Article · Dec 2011 · Supportive Care in Cancer
[Show abstract][Hide abstract] ABSTRACT: To provide a synopsis of current thalassaemia major patient care in Hong Kong.
All haematology units of the Hospital Authority in Hong Kong.
All patients with thalassaemia major with regular transfusion.
To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy.
The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.
No preview · Article · Aug 2011 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine
[Show abstract][Hide abstract] ABSTRACT: To provide a synopsis of current haemophilia care in Hong Kong.
All haematology units of the Hospital Authority in Hong Kong.
All patients with haemophilia A and haemophilia B.
To date, there were 222 mild-to-severe haemophilia patients (192 type A, 30 type B) under regular public care in Hong Kong (43% were considered severe, 33% moderate, and 24% mild), which gave a crude prevalence of 6.8/100 000 male inhabitants. A total of 12.8 million units of Factor VIII and 3 million units of Factor IX were prescribed annually. This amounts to 1.83 units of FVIII per capita of the population, which is comparable to that of other developed countries. Leading causes of mortality were human immunodeficiency virus-related complications (10 cases) and cerebral bleeding (2 cases). The life expectancy of patients with severe haemophilia in Hong Kong is improving; currently the oldest patient is 60 years old. Such improved survival may be due to enhanced factor availability, prompt treatment of bleeding episodes at home, safer factor products, and better antiviral treatment. Primary prophylaxis is the accepted standard of care for severe and moderate cases, and "Factor First" has become hospital policy. However, 12 patients continue to present treatment challenges, due to the documented presence of factor inhibitors. In all, 28, 100, and 14 cases respectively were positive for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus; the youngest patients with the corresponding infections being 28, 13, and 22 years old. Comprehensive care with dedicated physiotherapy, surgical support, and radionucleotide synovectomy may reduce morbidity further.
A multidisciplinary approach can further improve the future care for haemophilia patients in Hong Kong.
No preview · Article · Jun 2011 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine
[Show abstract][Hide abstract] ABSTRACT: There is a dearth of studies with respect to oral mucositis (OM) in the paediatric and adolescent populations. The purpose of this prospective cohort study was to examine the incidence and risk factors associated with OM in paediatric and adolescent patients receiving chemotherapy. OM assessments were made daily until 14days after chemotherapy using the self-report Mouth and Throat Soreness-Related Questions of the Oral Mucositis Daily Questionnaire (OMDQ MTS). Potential risk factors included age, gender, prior OM, anxiety level, cancer diagnosis, nausea/vomiting, use of growth factor, neutrophil count, liver enzymes, and creatinine value. Multiple logistic, Cox proportional hazards, and ordinal regression analyses were used to determine risk factors for the incidence and time to onset of MTS scores of ⩾2, and MTS scores across 14days by AUC categories, respectively, after adjusting for chemotherapy. A total of 140 patients who were 6-18years of age were evaluated. Forty-one percent (95% CI, 32.6-48.8%) developed OM; of these, 23% and 18% reported a maximum MTS score of 2 and 3-4 as the worst OM, respectively. The mean time to onset of OM was 4.7±2.7days with a mean duration of 6.3±4days. Prior OM (RR 1.90-3.94), a higher level of anxiety (RR 1.27-1.46), WHO grade 1-2 (RR 1.86-4.59) and 3-4 (RR 3.08-9.19) neutropenia were significantly associated with a higher probability of the incidence, earlier onset, and greater severity of OM, after controlling for chemotherapy (p<0.01). OM was associated with indirect cytotoxicity, prior OM, and anxiety level after controlling for chemotherapy where neutropenia was found to be the most important factor.
[Show abstract][Hide abstract] ABSTRACT: Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.
[Show abstract][Hide abstract] ABSTRACT: Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.
Full-text · Article · Jun 2008 · American Journal of Hematology
[Show abstract][Hide abstract] ABSTRACT: To study the outcome of children with acute lymphoblastic leukaemia who were treated using a protocol including one or two delayed intensifications.
Prospective single-arm multicentre study.
Five designated children cancer units of the Hospital Authority of Hong Kong.
Children aged between 1 and 17.9 years with newly diagnosed acute lymphoblastic leukaemia seen from November 1997 to December 2002.
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.
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.
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 HKALL97 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).
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.
Full-text · Article · Mar 2006 · Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine
[Show abstract][Hide abstract] ABSTRACT: The use of coagulation factor concentrates remains the mainstay treatment for haemophilias. Prothrombin complex concentrates, plasma-derived products that contain other vitamin K-dependent factors additional to factor IX, have been used for treatment of haemophilia B since 1959. However, they carry a small but significant risk of thromboembolic complications, and fatalities subsequent to myocardial infarction have been reported. We recommend that highly purified plasma-derived or recombinant products of factor IX concentrates should be the treatment of choice for patients with haemophilia B, especially those who are at higher risk for thromboembolism.
Full-text · Article · Jan 2006 · Hong Kong Journal of Paediatrics