[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.
[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.
Supportive Care in Cancer 03/2013; 21(8). DOI:10.1007/s00520-013-1772-0 · 2.36 Impact Factor
[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.
[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.
Supportive Care in Cancer 12/2011; 20(10):2335-42. DOI:10.1007/s00520-011-1343-1 · 2.36 Impact Factor
[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.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 08/2011; 17(4):261-6. · 0.87 Impact Factor
[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.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 06/2011; 17(3):189-94. · 0.87 Impact Factor
[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.
American Journal of Hematology 06/2008; 83(6):458-64. DOI:10.1002/ajh.21150 · 3.80 Impact Factor
[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.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 03/2006; 12(1):33-9. · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 09/2002; 8(4):255-60. · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hypothesis that protection of infants from exposure to infectious agents with delayed first exposure to one or more specific agents together contribute to the aetiology of childhood leukaemia, especially common acute lymphoblastic leukaemia (cALL), has substantial indirect support from descriptive epidemiology and case–control studies in developed Western countries. A case–control study of childhood leukaemia diagnosed at ages 2–14 years has now been conducted in Hong Kong. Cases (n = 98) formed a consecutive series of Chinese children diagnosed with acute leukaemia; controls (n = 228) were identified following a survey using random digit dialling and required to attend for medical examination by a paediatrician. Interviews with mothers were conducted in hospital by one trained interviewer using a structured questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) are reported for exposure variables capable of serving as proxies for exposure to infection in two critical time periods: first year of life, year before reference date (diagnosis for cases, corresponding date for controls). Analyses used logistic regression with adjustment for appropriate confounders.
Change of area of residence reduced risk if during the first time period (OR = 0.47 [95% CI 0.23, 0.98]) and increased risk if during the second (OR = 3.92, [95% CI 1.47, 10.46]). Reported roseola and/or fever and rash in the first year of life reduced risk (OR = 0.33 [95% CI 0.16, 0.68]) whereas tonsillitis in the period 3–12 months before reference date increased risk (OR = 2.56 [95% CI 1.22, 5.38]). Some other proxies for exposure to infection at the critical times were associated with predicted patterns of risk but day-care attendance failed to show predicted associations. These results provide support for the delayed exposure hypothesis in an affluent geographical setting in which population exposure to infectious agents is quite distinct from the settings of previous case–control studies.
[Show abstract][Hide abstract] ABSTRACT: A 21-month-old girl with hemoglobin Bart's hydrops received bone marrow transplantation (BMT) from a matched sibling. No major BMT-related complications developed. Hemoglobin levels remained greater than 10 gm/dl for 20 months without blood transfusion support despite the presence of residual host hemopoietic cells from 2 months after BMT. We suggest consideration of this therapeutic option for surviving patients.
Journal of Pediatrics 07/1998; 132(6):1039-42. DOI:10.1016/S0022-3476(98)70406-8 · 3.79 Impact Factor