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Purpose: Craniopharyngioma is a rare low-grade neoplasm in children. Tumor progression occurs frequently, and survivors are at risk of long-term disease and treatment-related morbidities. We reviewed the population-based experience of managing pediatric craniopharyngioma in Hong Kong., Methods: The Hong Kong Pediatric Hematology/Oncology Study Group database was interrogated for patients with craniopharyngioma younger than 18 years between 1999 and 2018. Patient demographics, clinical characteristics, outcomes, and long-term morbidities were summarized., Results: Twenty-eight patients with craniopharyngioma were included (approximate incidence of 1.1 per 1,000,000 individuals). The treatment approaches were heterogeneous and included surgery only, surgery with adjuvant radiation, and surgery with intracystic interferon. With a median follow-up of 6.1 years, 12 (43%) patients experienced disease progression, and 3 patients died of progression, postoperative complication, and gastrointestinal bleeding. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 56.8% (± 10.0%) and 92.0% (± 5.4%), respectively. The 10-year PFS and OS rates were 37.3% (± 11.4) and 92.0% (± 5.4%), respectively. Patients receiving treatment in a high-volume center had significantly better outcomes than did those treated at other centers (PFS, p = 0.007; OS, p = 0.029). Period of diagnosis, sex, age at diagnosis, greatest tumor dimension, extent of resection, and radiotherapy use did not significantly affect patient survival. Long-term visual impairment (60%) and endocrinopathies (92%) were common., Conclusion: Prognosis of pediatric craniopharyngioma in Hong Kong compares unfavorably with published reports. Centralization and standardization of treatment may prove valuable in mitigating patient outcomes.

Double-unit umbilical cord blood (DU-UCB) may extend the use of UCB transplantation and improve clinical outcomes. Data in the literature show that single-unit dominance happened in a vast majority of recipients, and the mechanism is unknown. We examined the clinical relevance and engraftment kinetics of DU-UCB transplant in 65 consecutive children who underwent unrelated single-unit (n = 25) and double-unit (n = 40) UCB transplantation for various hematological malignancies (n = 45) and nonmalignant disorders (n = 20). Our result showed no discernible benefit to children receiving double-unit transplant over those receiving single-unit transplant when the total nucleated cell (TNC) doses are ≥2.5 × 10(7)/kg, in terms of the hastening of the engraftment of neutrophils and platelets, reduction of nonengraftment, disease recurrence, early mortality, and graft-versus-host disease, despite significantly higher numbers of TNCs in double units. Further analyses demonstrated that the phenomena were not associated with underlying disease, duration of UCB storage, postthaw viability, HLA disparity, ABO incompatibility, gender, or doses of TNCs, CD34(+) cells, CD3(+) cells, or colony-forming units. Engrafting units in DU-UCB transplants were notably associated with higher CD34(+) cell dose. Chimerism studies demonstrated that single-unit dominance started before neutrophil engraftment in DU-UCB transplants. Data from the study suggested no advantage of infusing double-unit UCB, if an adequately dosed single-unit UCB is available. Successful prediction of the dominant graft would optimize algorithms of UCB selection and maximize the long-term engraftment of chosen units.

The management of central nervous system tumors in children below the age of 3 years represents a 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 in Hong Kong between 1999 and 2011. Eighty-one children with primary central nervous system tumors from 0 to 3 years of age were identified (annual incidence: 4.16 cases per 100,000). Forty-one (50.6%) were male and the mean duration of follow-up 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), choroid plexus tumor (n=7), primitive neuroectodermal tumor (n=7), atypical teratoid rhabdoid tumor (n=6), germ cell tumor (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 1-year overall survival (OS), 5-year OS, 1-year event-free survival (EFS), and 5-year 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 atypical teratoid rhabdoid tumor/primitive neuroectodermal tumor 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.

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., Procedure: 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., Results: 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%., Conclusions: 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.

Familial haemophagocytic lymphohistiocytosis is a rare but invariably fatal disease without haematopoietic stem cell transplantation. Genetic defect identification is useful for confirming a clinical diagnosis, predicting the risk of future recurrence, and defining haemophagocytic lymphohistiocytosis predisposition in asymptomatic family members. Notably, familial haemophagocytic lymphohistiocytosis type 2 associates with mutations in the perforin gene (PRF1) which is the most frequent subtype of familial haemophagocytic lymphohistiocytosis. Although perforin gene mutations have been described in Asians, they are largely reported from Japan. The case reported here is the first familial haemophagocytic lymphohistiocytosis type 2 patient in Hong Kong with an identified perforin gene mutation.

Background: Several trials incorporating adjuvant focal RT for treatment of young children with ependymoma have demonstrated improved survival with acceptable adverse effects. The optimal timing of RT administration is, however, unknown., Procedure: A retrospective review of territory-wide database was performed to identify pediatric patients with ependymoma diagnosed between 1995 and 2011. OS and EFS were compared between patients receiving upfront RT (<150 days of diagnosis), delayed RT (≥150 days of diagnosis), or no RT., Results: Thirty-one patients with intracranial ependymoma were identified. Median age was 3.5 years and 14 (45%) were male. Primary tumor was supratentorial in 10 (32%) and infratentorial in 21 (68%). All patients underwent initial surgery, with gross-total resection (GTR) in 27 (87%). Twelve (39%) received upfront RT, 10 (32%) had delayed RT and 9 (29%) had no RT. During the study period, there were 11 relapses (35%) and 10 deaths (32%). Five-year OS was 69.9% and 5yr-EFS was 49.3%. In univariate analysis, GTR led to improved OS (P < 0.001) and EFS (P = 0.004); superior OS and EFS was observed in patients who received RT when compared with those without (P = 0.018 and 0.011, respectively). Upfront RT also resulted in better OS and EFS than delayed RT (P = 0.049 and 0.014, respectively). No significant effect on survival was observed with age, sex, tumor location, RT dosage, and protocol used. In multivariate analysis, GTR significantly improved OS (P = 0.002) and EFS (P = 0.004)., Conclusions: Our results support the early initiation of adjuvant RT in the multi-modal management of pediatric ependymomas., (© 2013 Wiley Periodicals, Inc.)

Background: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales are commonly used to assess health-related quality of life of healthy children and pediatric patients. Validation of the Generic Core Scales among Chinese pediatric cancer patients has not been reported in the literature. The scales can serve to measure different quality-of-life domains that are not captured by the PedsQL Cancer Module., Objective: Psychometric properties of the Chinese version of the PedsQL 4.0 among pediatric cancer patients and their caretakers were examined., Methods: The Generic Core Scales were administered to 335 pairs of pediatric cancer patients (aged 8-18 years) and their caretakers in Hong Kong., Results: A 5-factor structure (physical, emotional, social, school-related cognitive function, and missed school) was identified in the patient and proxy versions of the scales using confirmatory factor analysis. Both versions of the total scale reported Cronbach α's of .90 or greater, with almost all subscales reporting α's of .70 or greater. Test-retest reliability at 2 weeks was acceptable (intraclass correlations ≥0.60) for a majority of subscales. Agreement between patients' and caretakers' ratings was medium., Conclusions: The scales demonstrated acceptable psychometric properties and construct validity., Implications for Practice: This study validated the Chinese version of the Generic Core Scales among pediatric cancer patients and their caretakers, which supports the future use of the scales in clinical settings. The Generic Core Scales can also be supplementary to the PedsQL Cancer Module for measuring multiple domains of quality of life in cancer population.

Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1-10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15 ≥ 10% or day-33 ≥ 0.01% but not both, II-C: day-15 ≥ 10% and day-33 ≥ 0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD ≥ 10(-4) were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients' prognosis, with 20-35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥ 10(-4). We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring.

Background: Despite neoadjuvant chemotherapy and wide surgical ablation, 15% to 25% of patients with primary osteosarcoma will relapse (local recurrence or metastases). Neither chemotherapy nor radiation therapy alone will render a patient disease-free without concomitant surgical ablation of relapse. We prefer excision of relapse when possible. However, it is unclear whether excision enhances survival., Questions/purposes: We therefore determined (1) onset, location, and treatments for relapse; (2) postrelapse disease-free survival of patients who underwent surgical ablation and those who did not; and (3) relapse-free interval between initial diagnosis and first relapse in survivors and in those who died of their disease., Methods: We retrospectively reviewed 15 children who initially presented with localized, nonmetastatic extremity osteosarcoma and attained initial complete remission after neoadjuvant chemotherapy, wide local resection, postoperative chemotherapy, and subsequently developed disease relapse. Relapse occurred at a median of 28 months, although late relapse after 5 years occurred in three. We resected the recurrent tumor in nine patients and treated six nonoperatively., Results: Seven of nine surgically treated patients had a postrelapse disease-free survival ranging from 3 to 14 years and an overall survival ranging from 7 to 16 years. Patients not surgically treated all died within 40 months of their relapse. The median relapse-free interval in patients who survived was longer 34 months (range, 17-152 months) as compared with 17 months (range, 7-40 months) in those who died of their disease., Conclusions: Our data confirm the importance of surgery in patients with relapsed osteosarcoma. Disease-free survival in patients with relapsed osteosarcoma is only possible if complete remission is attained. Patients with late relapse may have a better chance of survival., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Central venous catheterization is essential in the management of patients requiring long-term intravenous access. Various risks during central line insertion have been described in the medical literature, including the potentially life-threatening complication of iatrogenic arteriovenous fistula (AVF). We describe a novel case of carotid jugular AVF following implanted port (BardPort® by C.R. Bard, Inc.) insertion in a pediatric oncology patient who had suffered cerebral infarct due to thromboembolism. Pediatr Blood Cancer 2012; 59: 1302-1304. © 2012 Wiley Periodicals, Inc., (Copyright © 2012 Wiley Periodicals, Inc.)

Secreted-frizzled related proteins (SFRPs) are modulators of the Wnt signaling pathway that is closely involved in normal and malignant hematopoiesis. Epigenetic deregulation of Wnt modulators leading to aberrant signaling has been reported in adult patients with acute myeloid leukemia (AML), but its occurrence in childhood patients with AML and the role of individual modulators are unclear. In this study, we examined SFRP1, SFRP2, SFRP4, and SFRP5 promoter methylation in 83 patients with AML (59 children and 24 adults) and found preferential SFRP1 methylation and mRNA down-regulation in the prognostically favorable subgroup of AML with t(8;21) translocation. Among the 4 genes, SFRP1 methylation independently predicted prolonged event-free and relapse-free survivals in childhood patients with nonacute promyelocytic leukemia with nonadverse cytogenetics. Mechanistically, we further demonstrated that RUNX1-ETO, the t(8;21) fusion product, specifically bound the SFRP1 promoter and repressed its transcription via a consensus RUNX binding site. In t(8;21)-leukemia cells, SFRP1 selectively inhibited canonical Wnt signaling and cellular proliferation that were associated with concomitant down-regulation of Wnt/β-catenin target genes, including CCND1 and MYC. Taken together, we identified SFRP1 as a transcriptional repression target of the t(8;21) fusion protein and demonstrated a novel mechanism of Wnt activation in a specific subtype of AML.

Objective: To evaluate the initial presenting symptoms and management of osteosarcoma in Hong Kong Chinese children, in relation to any possible impact on disease outcomes., Design: Retrospective study., Setting: A tertiary referral centre of bone cancer in a university teaching hospital in Hong Kong., Patients: All children aged younger than 18 years with a diagnosis of osteosarcoma who received treatment from March 1994 to October 2005., Results: A total of 51 children were studied. The median age of onset was 13 (range, 3-20) years; 61% were males. The tumours were located in the distal femur and proximal tibia, which accounted for 45% and 22% of the cases, respectively; 24% of patients had metastatic disease at presentation. Swelling (76%) and pain (90%) were the most common presenting complaints. Approximately one third of the patients had a preceding history of trauma. The median duration of initial symptoms to first medical consultation of any sort was 30 (range, 0-360) days. The median time from the first consultation to a definitive diagnosis was 21 (range, 0-350) days; 25% were diagnosed more than 52 days after presentation. Bonesetters were initially consulted by 37% of these patients. From presentation to diagnosis, the median duration was 61 (range, 4-361) days. Analysis of the duration of pre-diagnosis symptoms did not correlate significantly with the development of metastatic disease, response to chemotherapy, feasibility of limb salvage surgery, relapse rates, or survival rates., Conclusions: In Hong Kong, initial consultation to bonesetters was common. A relatively long delay in between symptom onset and diagnosis of osteosarcoma was encountered. The public and medical practitioners should be made aware of this disease, especially in adolescents.

Beta thalassaemia major is a common hereditary haematological disease in southern Chinese. Advances in transfusion and iron chelation improve survival but haematopoietic stem cell transplantation (HSCT) is still the only curative treatment. Due to repeated blood transfusion and iron overload, thalassaemia patients undergoing HSCT are at a higher risk of graft rejection and transplant-related mortality. The prognostic factors identified to be affecting transplant outcome include hepatomegaly, hepatic fibrosis, and compliance to chelation therapy. Patients can be classified into three classes and conditioning regimens are modified according to the risk. Early stage patients have 85 to 90% chance of disease-free survival, whereas advance stage only has 60% disease-free survival. Mixed chimerism is common after HSCT but majority have satisfactory erythropoiesis without need for further transfusion. Sibling cord blood and bone marrow transplantation has similar outcome. Recently alternative donor transplant has been performed in patients without human leukocyte antigen (HLA)-identical siblings. The result of unrelated-donor bone marrow transplantation is in general inferior but extended HLA matching may improve outcome. The use of unrelated cord blood transplant from a single-centre study showed promising result. The survivors require iron depletion to remove excessive iron store and some may require hormonal replacement therapy. Most of the patients have good quality of life after successful HSCT.

We report the case of a 12-year-old girl with a strong family history of malignancy who presented with immature teratoma and gliomatosis peritonei. Despite first and second line chemotherapy, the disease ran an unusually refractory course. Although the presentation was not the typical tumour presentation of Li-Fraumeni syndrome (LFS), we proceeded to undertake tumour genetic testing of the patient and her parents. LFS was diagnosed in this patient and her father with a sequence variation of CGG>TGG, R248W, which is one of the most common transcriptionally inactive mutations detected in LFS. Genetic counselling was offered to the father. A tumour screening programme and genetic screening for the p53 gene mutation for the surviving family members can be offered once consent is obtained from the father. This case illustrates the importance of cancer genetic study, even if the tumour presentation is not typical for any familial cancer syndrome.

Osteoporosis is a common complication in thalassemia major (TM). Our previous study demonstrated severe bone mineral density (BMD) deficits at spine and hip in 62 and 35% of TM patients. This study assessed the effects of different treatments (calcium, vitamin D and bisphosphonate) on patients' BMD, which was measured at baseline and after 3-year treatments by dual energy X-ray absorptiometry (DEXA). Twenty-one untreated patients, 11 patients on calcium/vitamin D and seven patients on additional pamidronate, were recruited. They were comparable for gender (p = 0.630) and serum ferritin levels (p = 0.412). The median BMD Z-scores at lumbar spine and left hip improved only in patients with standard plus pamidronate treatments (baseline: -3.01 and -3.05, end-of-study: -2.12 and -2.09; p = 0.018 and 0.028, respectively). In contrast, BMD Z-scores at hip worsened in untreated patients (p = 0.034). In conclusion, long-term improvement in BMD in TM patients was observed with bisphosphonate but not calcium and vitamin D treatment.

RUNX3/AML2 is a Runt domain transcription factor like RUNX1/AML1 and RUNX2/AML3. Regulated by 2 promoters P1 and P2, RUNX3 is frequently inactivated by P2 methylation in solid tumors. Growing evidence has suggested a role of this transcription factor in hematopoiesis. However, genetic alterations have not been reported in blood cancers. In this study on 73 acute myeloid leukemia (AML) patients (44 children and 29 adults), we first showed that high RUNX3 expression among childhood AML was associated with a shortened event-free survival, and RUNX3 was significantly underexpressed in the prognostically favorable subgroup of AML with the t(8;21) and inv(16) translocations. We further demonstrated that this RUNX3 repression was mediated not by P2 methylation, but RUNX1-ETO and CBFbeta-MYH11, the fusion products of t(8;21) and inv(16), via a novel transcriptional mechanism that acts directly or indirectly in collaboration with RUNX1, on 2 conserved RUNX binding sites in the P1 promoter. In in vitro studies, ectopically expressed RUNX1-ETO and CBFbeta-MYH11 also inhibited endogenous RUNX3 expression. Taken together, RUNX3 was the first transcriptional target found to be commonly repressed by the t(8;21) and inv(16) fusion proteins and might have an important role in core-binding factor AML.

Haemophagocytic lymphohistiocytosis is a rare but potentially fatal disease. Diagnosing this disease may be difficult and is often delayed because the clinical presentation mimics other conditions like severe sepsis, hepatic failure and malignancies. We reviewed the clinical presentations, response to treatment, and outcomes of children diagnosed with haemophagocytic lymphohistiocytosis from 1991 to 2006 in a Hong Kong tertiary paediatric haematology centre. All patients had typical presentations with prolonged fever, organomegaly, and pancytopaenia. Six children had hepatic dysfunction and two had neurological symptoms. The median time from disease onset to diagnosis was 21 days. Elevated serum ferritin levels and evidence of haemophagocytosis in bone marrow examinations aided diagnosis. The overall mortality was 57%. Three patients who presented in the first few years studied had relatively long lag times between disease onset and definitive treatment; all died of active disease. Three patients diagnosed more recently were given timely treatment using the haemophagocytic lymphohistiocytosis-94 protocol of etoposide and dexamethasone, with or without cyclosporin. All three achieved remission, but two had a recurrence and one died during the recurrence.

We describe a case of coexisting BCR-ABL negative myeloproliferative disorder and precursor T-cell lymphoblastic lymphoma associated with t(8;13) involving FGFR1 at 8p11 in a 14-year-old boy who presented with generalized lymphadenopathy and an abdominal mass. JAK2 mutation and FIP1L1-PDGFRalpha were not detected. RT-PCR revealed the ZNF198-FGFR1 fusion transcript in both the bone marrow (BM) and lymph node (LN) of the patient at diagnosis. Of interest, reciprocal FGFR1-ZNF198 fusion transcript was demonstrated in the BM but not LN. Also differential clonal TcRgamma gene rearrangements in the BM and LN samples were observed. These findings provide novel insights into the genetic pathogenesis.

We performed a retrospective analysis on the human leukocyte antigen (HLA) data of 53 consecutive Chinese patients with high-risk childhood acute lymphoblastic leukemia (ALL) diagnosed from 1989 to 2003. A significantly higher frequency of HLA-B67 in the male relapse group of patients [OR, 23.08; 95% CI, 5.31-100.36; p = 0.0042; for statistical significance after Bonferroni correction (Bc) p (Bc) < 0.0083] was identified after Bonferroni correction. Although not surviving the Bonferroni correction, gender effects on the association were also observed with HLA-A11, HLA-A32, HLA-A33, and HLA-B22, which were however more prevalent in the female patients and particularly those developing relapse. Two patients with HLA-A29 and HLA-B7 revealed significantly shortened survivals, suggestive of their potential prognostic impacts. Notably, for the first time, we found a significant correlation of leukocyte count with HLA types, where HLA-A33 (p = 0.006) or HLA-B17 (p < 0.001) signifies higher leukocytosis at presentation. Taken together, our findings support the involvement of HLA in Chinese high-risk childhood ALL.

We describe two pediatric patients who developed autoimmune hypothyroidism 2 years after unrelated allogeneic hematopoietic stem cell transplantation. The causes of post-transplantation autoimmune hypothyroidism are probably multiple. In these two patients, the presence of chronic graft-versus-host disease may be the most significant contributing factor.

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 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)., 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.

Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450; P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients., (Bone Marrow Transplantation (2005) 36, 331-336.)

Arsenic trioxide (ATO) induces apoptosis in a range of solid tumors and leukemia cells, and has been clinically applied for the treatment of acute promyelocytic leukemia with confirmed efficacy. Acute megakaryocytic leukemia (AMKL) is an aggressive malignancy with poor prognosis, if bone marrow transplantation is not possible. In this study, we applied flow cytometry, Western blot analysis and microarray techniques to investigate the effects of ATO on apoptosis and the cell division cycle of AMKL cell lines CHRF-288-11 and MEG-01. Our data demonstrated that ATO is a potent agent against AMKL as indicated by apoptotic markers, Annexin V and caspase-3. ATO activated the intrinsic (mitochondrial) pathway of apoptosis, which involved disrupting mitochondrial membrane potential, increased Bax/Bcl-2 ratio and caspase-9 activation, as well as the extrinsic (death receptor) pathway mediated by Fas and caspase-8 activation. We provided the first evidence that ATO stimulated expressions of CD137 mRNA and protein, which might be relevant to the extrinsic mechanism. ATO induced delays of cell cycle progression at S phase and arrest at G2/M phase of AMKL cells, but caspase-3 expression appeared not to be phase-specific. The multiple-signaling mechanism of ATO warrants it a potential agent to incorporate in the treatment regimen of AMKL.

Objectives: Ex vivo expansion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) is a promising approach for overcoming the developmental delay of bone marrow (BM) reconstitution after transplantation. This project investigated the effects of culture duration, serum-free media, cytokine combinations, and chemotherapy on the outcomes of expansion., Methods: Enriched CD34+ cells were cultured for 8 or 10 d in serum-free media (QBSF-60 or X-Vivo 10) and four combinations of cytokines consisting of recombinant human pegylated-megakaryocyte growth and development factor, stem cell factor, flt-3 ligand, G-CSF, interleukin (IL)-6, platelet-derived growth factor (PDGF), and IL-1beta., Results: Eight days of culture in QBSF-60 significantly supported efficient expansions of CD34+ cells, CD34+ CD38- cells, colony-forming units (CFU) of myeloid, erythroid, megakaryocytic, and mixed lineages to 3.76-, 14.4-, 28.3-, 24.0-, 38.1-, and 15.7-fold, respectively. Whilst PDGF or IL-6 enhanced the expansion of early, myeloid, and erythroid progenitors, IL-1beta specifically promoted the megakaryocytic lineage. Engraftment of human CD45+ cells were detectable in all non-obese diabetic/severe-combined immunodeficient mice transplanted with expanded PBSC from donor samples, being 5.80 +/- 3.34% of mouse BM cells. The expansion and engraftment capacity of CD34+ cells from subjects postchemotherapy were significantly compromised across the panel of progenitor cells., Conclusion: Our results provided an optimized protocol for PBSC expansion, applicable to ameliorating neutropenia and thrombocytopenia in post-BM transplant patients by the prompt provision of progenitor cells. For postchemotherapy patients, expansion products might provide committed progenitors for improving short-term engraftment, but not self-renewable stem cells., ((c) Blackwell Munksgaard 2005)

We analyzed 43 consecutive cases of pediatric acute myeloid leukemia (AML) for the presence of the CBFbeta-MYH11 rearrangement using molecular techniques in a regional hospital in Hong Kong. Five cases (11.6%), 3 girls and 2 boys, ranging in age from 8 months to 14 years old, were found positive for the CBFbeta-MYH11 rearrangement. Morphologically, they were FAB M2 or M4 with or without eosinophilia (Eo). Typical M4Eo was observed in only one case. The molecular findings were in complete concordance with cytogenetic data, which revealed inv(16)(p13q22) in all and also gains of chromosome 4, 8, 22, and Y in one patient. Clinically, all 5 patients achieved complete remission after chemotherapy with favorable outcomes except for the patient with infantile AML, who relapsed 11 months after diagnosis, underwent cord blood transplantation, and was in second remission. This is the first clinicopathological study and documentation of the incidence of CBFbeta-MYH11 in childhood AML of Chinese in Hong Kong., (Copyright 2004 Wiley-Liss, Inc.)

Thalassemia major (TM) patients frequently suffer from growth delay and endocrine dysfunction. Thirty-two TM patients who had survived more than 2 years after bone marrow transplantation (BMT) were recruited for growth and endocrine study. Patients were followed up annually for growth, and the height was expressed as height standard deviation score (HtSDS). The HtSDS at baseline was -1.51 and was more reduced in patients older than 7 years (-1.99) as compared with those younger patients (-0.79) (p =.027). The HtSDS gradually improved after BMT and increased by 0.59 (CI 0.16-1.01) at 5 years after BMT. Forty percent of patients were below 2 SD at time of BMT but this decreased to 15% at the latest assessment. The hormonal profiles of gonadotrophins, sex hormones, and thyroid function were assayed regularly after BMT. With a median follow-up of 67 months, ovarian failure was universal among the 10 girls evaluable for puberty and all required hormonal replacement. Eight of 10 boys had spontaneous puberty but 3 of them had gonadal impairment. One patient developed diabetes mellitus and one had growth hormone deficiency after BMT. In conclusion, improvement of growth after BMT in TM was common. Gonadal failure is universal in girls, and boys were less affected.

Objective: To review the outcome of unrelated umbilical cord blood transplantation in children using cord blood from the Hong Kong Red Cross Blood Transfusion Service., Design: Retrospective study., Patients: Records of eight patients who received unrelated umbilical cord blood transplants between 1999 and 2003 were reviewed., Main Outcome Measures: Engraftment of haematopoietic cells and graft-versus-host disease after transplantation., Results: The median age of the patients was 4.9 years (range, 1.0-9.4 years). Five patients had acute leukaemia, one had non-Hodgkin's lymphoma, one had X-linked adrenoleukodystrophy, and one had mucolipidosis. The infused umbilical cord blood units contained a median of 6.7 x 10(7) /kg nucleated cells and 4.0 x 10(5) /kg CD34-positive cells. Neutrophil engraftment was achieved at a median of 13 days (range, 11-19 days) and, for seven patients, platelet engraftment was achieved at a median of 39 days (range, 24-98 days). Acute graft-versus-host disease occurred in all patients (grades I to III). One of the patients died because of encephalitis; of the other seven, five developed chronic graft-versus-host disease of the skin. At a median follow-up of 2 years, the four patients with leukaemia and the one with non-Hodgkin's lymphoma remained in continuous complete remission; the patient with adrenoleukodystrophy showed stabilisation of neurological condition., Conclusion: The Hong Kong Red Cross Blood Transfusion Service Cord Blood Bank stored cord blood units of good quality for transplantation, the outcome of which was comparable to that of bone marrow transplantation.

Human herpesvirus 7 (HHV-7) is the least studied beta-herpesvirus in transplant settings. This prospective study examined the activity of HHV-7 during the first 12 weeks post-stem cell transplant in 59 paediatric patients. The presence of HHV-7, human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6) in blood was monitored weekly by a multiplex nested polymerase chain reaction. Overall, 33 (55.9%) patients had one or more surveillance blood sample(s) positive for HHV-7. In contrast to HCMV and HHV-6, no obvious peak time of reactivation was observed for HHV-7. The occurrence of HHV-7 DNAaemia showed a significant negative association with HHV-6 (P=0.022), but with no association with HCMV. A significant higher positive rate for HHV-7 was found in autologous versus allogeneic (P=0.002), and in peripheral blood versus umbilical cord/marrow (P<0.001) transplant. Acyclovir had no effect, whereas ganciclovir was associated with a lower rate of HHV-7 reactivation (P=0.009). One patient died of HHV-7 associated brain stem encephalitis. The administration of colony stimulating factor, occurrence of acute graft versus host disease, time to neutrophil and platelet engraftment showed no significant association with the occurrence of HHV-7 DNAaemia., (Copyright 2004 Wiley-Liss, Inc.)

Objective: To determine the role of oseltamivir prophylaxis for immunocompromised patients., Design: Prospective, non-blinded, non-controlled observational study., Setting: A paediatric cancer centre, Hong Kong., Participants: Thirty-two patients, immunocompromised by chemotherapy or bone marrow transplantation during an influenza season in 2001., Intervention: Oral oseltamivir prophylaxis 75 mg/d for 8 weeks., Main Outcome Measures: Laboratory-confirmed influenza infection, symptoms of influenza, drug compliance, and any side-effects from oseltamivir treatment. Laboratory monitoring included virological surveillance for influenza A and B, blood counts, and renal and liver function tests., Results: Patients' median age was 14.3 years (range, 6.3-23.4 years). Underlying conditions included malignancy (n=29) and other haematological diseases (n=3). No documented influenza infection according to serological tests was present throughout the study period. Five patients with symptoms of upper respiratory tract infection did not have any influenza infection detected by rapid virological assay and viral culture. For 16% of patients, the main side-effect in the study was gastro-intestinal upset., Conclusions: Oral oseltamivir 75 mg once daily for 8 weeks may be useful in the prevention of influenza infection in patients immunocompromised by chemoradiotherapy; side-effects are few and acceptable.

Objective: To correlate serum cytokine levels and the development of acute graft-versus-host disease (GVHD), the authors conducted a prospective study on serial measurements of interferon (IFN)-gamma and interleukin (IL)-10, IL-12 and IL-15., Methods: The cytokines were measured in 27 subjects by enzyme-linked immunosorbent assay serially for the first 2 months after hematopoietic cell transplantation., Results: Nineteen subjects with acute GVHD had significantly higher mean peak serum levels of IFN-gamma and IL-15 than the baseline levels at the start of conditioning. The peak level occurred soon after stem cell infusion and returned to the pretransplantation state in the second month. In contrast, there was lesser difference between the mean peak serum levels of IFN-gamma, IL-10, and IL-15 and the baseline level in the eight subjects without GVHD. The peak serum level for IL-15 was, in addition, significantly higher among GVHD subjects than those without GVHD in the first month posttransplantation. However, the level of IL-15 showed no correlation with the severity of GVHD., Conclusions: These changes point to a possible role of systemic cytokine secretion in the development of acute GVHD. Elevated levels of IL-15 early in the posttransplant period could be a helpful laboratory predictor of acute GVHD.

Thrombospondin-1 (TSP-1) is a naturally occurring anti-angiogenic compound that induces apoptosis of endothelial and cancer cells via its receptor CD36. The objectives of our study were to investigate the in vitro effects of TSP-1 on the apoptosis of primary human leukemia cells as well as leukemia cell lines and the possible mechanism involving CD36. Our results demonstrated that TSP-1 induced apoptosis in CD36 positive cell lines CHRF-288-11, Meg-01 and HL-60, but not CD36 negative K562, at a dose-dependent manner as demonstrated by DNA ladder formation, Annexin V and propidium iodide (PI) stainings. The addition of anti-CD36 antibody FA6-152 or thrombopoietin (TPO) significantly nullified the effects of TSP-1. TSP-1-mediated apoptosis was consistently associated with the up-regulation of active Caspase-3. Responses of 2 CD36 positive primary AML samples to TSP-1 and FA6-152 were similar with those of leukemia cell lines. TSP-1 significantly induced apoptosis in B-ALL but the counter-effects of FA6-152 were less apparent. CD36 negative AML cells appeared less susceptible to TSP-1 and FA6-152. Our data provided strong evidence that TSP-1 exerted direct apoptotic effects on leukemia cells and could be developed as an adjunct to conventional therapy, particularly for leukemia cells that express CD36 or other TSP-1 receptors.

Glycoprotein B (gB) and glycoprotein H (gH) of human herpesvirus 7 (HHV-7) are believed to play an important role in virus entry and as targets for host immune response. This study examined the genetic diversity of these glycoproteins among 90 HHV-7 isolates collected from different individuals in Hong Kong. Overall, both the gB and gH genes were found to be highly conserved. Nucleotide polymorphism was detected only at four positions of the gB-encoding region, and all of these were synonymous substitutions. Most (97.8%) Hong Kong isolates were of gB allele group C. Two isolates collected from a Pakistani family showed a novel sequence pattern that did not match known gB allele groups. This sequence pattern was detected consistently from serial samples collected from the same individual, indicating a stable genetic entity. The gH-encoding region exhibited nucleotide polymorphism at six positions. Three of these were nonsynonymous substitutions (codon 271 Lys --> Gln, codon 308 Gly --> Glu, codon 397 Asn --> Tyr). Most (84.4%) Hong Kong isolates were of the gH allele group B, and all others were of the gH allele group C. These data indicate the possibility of using gB or gH alleles as markers for studying world-wide population movements and genetics., (Copyright 2003 Wiley-Liss, Inc.)

Background: The identification of neuroblastoma metastases to bone marrow (BM) is requisite in staging disease for risk-adopted therapy. However, micrometastases were not elucidated fully., Methods: Flow cytometry (FCM) with CD45/CD56/CD81 and reverse transcriptase-polymerase chain reactions (RT-PCR) for tyrosine hydroxylase (TH) transcripts were used to evaluate neuroblastoma in bilateral BM aspirates at diagnosis, BM autografts, peripheral blood stem cell (PBSC) collections, and CD34(+) cell products of 27 children., Results: TH transcripts were amplified in histology-negative (H(-)) BM specimens from seven patients (four patients with Stage 3 disease, two with Stage 4 disease, and one with Stage 4S disease), revealing a prevalence of submicroscopic metastasis. The median number of CD45(-)CD81(+)CD56(+) cells in four H(-) TH(-) BM samples from two patients with Stage 1 and Stage 2 disease, respectively, was comparable to that encountered in 10 normal BM controls (0.003% [range, 0.002-0.004%] vs. 0.004% [0-0.008%], P = 0.724). In six H(-) TH(+) BM specimens from three patients whom were otherwise diagnosed with neuroblastoma Stage 3, 0.031% (0.009-0.06%) CD45(-)CD81(+)CD56(+) cells were detected. Besides, 1.474% (0.088-3.009%) CD45(-)CD81(+)CD56(+) cells were identified in four H(-) TH(+) BM specimens from two patients at Stage 4. TH transcripts were evident in four of five BM autografts and in 22 of 45 (48.9%) PBSC specimens. FCM demonstrated 0.018% and 0.049% CD45(-)CD81(+)CD56(+) cells in two TH(+) BM autografts, respectively. The number of CD45(-)CD81(+)CD56(+) cells was higher in 19 TH(+) PBSC specimens than in 20 TH(-) PBSC specimens (0.026% [0.006-1.128%] vs. 0% [0-0.009%], P < 0.0001). CD34(+) cell selection achieved 2.9 (2.1-3.5) log depletion of CD45(-)CD81(+)CD56(+) cells in four manipulated products, rendering six of seven PBSC autografts TH-free., Conclusions: FCM in combination with RT-PCR evaluated neuroblastoma micrometastasis and assessed the purity of hematopoietic autografts for transplant. However, the clinical relevance remains to be elucidated., (Copyright 2003 American Cancer Society.)

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., (Copyright 2002 John Wiley & Sons, Ltd.)

Neurocutaneous melanosis is a rare congenital syndrome characterized by large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The prognosis is extremely poor for symptomatic patients, even in the absence of malignant melanoma. We present serial MR imaging findings in the brain and spine of a child with congenital giant hairy nevi who developed progressive leptomeningeal melanomatosis and whose neurologic condition rapidly deteriorated.

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.

A 13-year old girl suffering from beta-thalassaemia major received bone marrow transplantation (BMT) from her HLA identical bother. After initial engraftment, she developed mixed chimerism. Secondary graft rejection occurred at 10 months after BMT and resulted in marrow aplasia. A second transplant with the same bone marrow donor was performed. The patient was conditioned with antithymocyte globulin 90 mg/kg followed by peripheral blood stem cell infusion. There was prompt engraftment and patient reverted to complete chimerism. There were no severe treatment-related complications or acute or chronic graft versus host disease after second transplant. The patient remained transfusion independent at 26 months after second transplant.

Three children developed human herpesvirus-6 (HHV-6), variant B encephalitis after unrelated umbilical cord blood transplant, in a single center. They developed clinical manifestations of encephalitis around day 17 post transplant. Impairment of consciousness, incoherent speech, episodic focal pruritus, motor weakness, convulsions and severe hyponatremia were features at presentation. Radiological investigation of brain ranged from unremarkable to extensive white matter and meningeal lesions. Diagnosis was established by the presence of HHV-6 DNA in cerebrospinal fluid (CSF). Retrospective analyses of plasma revealed the presence of viral DNAemia prior to the onset of disease in two subjects. Treatment with ganciclovir or foscarnet was given. Two subjects did not achieve engraftment and died of other transplant-related complications on day 38 and 56 post-transplant, respectively. One subject achieved disease-free survival for more than 1 year with a satisfactory neurological outcome. In conclusion, HHV-6 encephalitis is not uncommon among patients undergoing umbilical cord blood transplantation. It is worth conducting further studies on early diagnosis and optimal management of this potentially fatal disease.

Aims: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers., Method: Liver biopsy was performed to assess the histological changes and liver iron content (LIC)., Results: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients., Conclusion: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

Previous studies have suggested a neuroinvasive and neuropersistent potential of human herpesvirus 7 (HHV-7). In this report, a case of fatal encephalitis is described and its association with HHV-7 infection is discussed. An 8-year-old girl received a peripheral blood stem cell transplant for relapsed acute lymphoblastic leukaemia. The post-transplant period was uneventful and a course of intrathecal chemotherapy was given on Day-30. On Day-41, she developed acute encephalopathy with diplopia and nystagmus. She ran a rapid downhill course and succumbed despite antiviral treatment. The only positive pathological finding was the multiple microscopic foci of haemorrhage associated with neuronal degeneration detected in the brain stem. All microbiological investigations were negative, except for the presence of HHV-7 DNA in cerebrospinal fluid and brain stem tissue samples., (Copyright 2002 Wiley-Liss, Inc.)

From August 1992 to August 1999, 44 patients received allogeneic haematopoietic stem cell transplantation in a single institution. The donors were HLA-identical siblings except for one who was a phenotypically matched father. Thirty-eight patients received bone marrow stem cells and the others received peripheral blood stem cells or umbilical cord blood (UCB). The mean age at transplant was 10.7+/-5.1 years, ranging from 1.8 to 21 years. Patients received busulphan (16 mg/kg) and cyclophosphamide (150 to 200 mg/kg) as conditioning, and antithymocyte globulin was given to 42 patients to prevent graft rejection. All had engraftment except a patient who received a UCB transplant. Four patients died from early treatment-related mortality, and one died from interstitial pneumonitis 3 months after transplant. Two patients developed secondary graft rejection and both received a second transplant. Thirty-eight patients survived and all except one were transfusion independent. The 5-year overall and event-free survival rates were 86% and 82%, respectively. By multivariate stepwise Cox proportional hazard analyses, severe veno-occlusive disease (VOD) of liver and Pesaro class 3 features were the significant factors associated with survival. Patients aged more than 11 years were more inclined to develop VOD. In conclusion, haematopoietic stem cell transplantation should be performed early if an HLA identical sibling is available.

The TEL/AML1 rearrangement has been implicated as an independent good prognostic factor in pediatric acute lymphoblastic leukemia (ALL). We examined TEL/AML1 using nested reverse-transcription polymerase chain reaction (RT-PCR) and correlated TEL/AML1 with cytogenetics and immunophenotypes in 75 consecutively analyzed Chinese children with ALL in Hong Kong. TEL/AML1 was detected in 17.9% (12/67) B-lineage ALL at diagnosis but not in 8 T-ALL children or in 34 adults with ALL. E2A/PBX1, MLL/AF4, and BCR/ABL were not found in TEL/AML1+ patients. Coexpression of cross-lineage antigens was associated with TEL/AML1 gene fusion (p = 0.032), with CD13 in 80% (4/5) TEL/AML1+ cohort. Chromosomal abnormalities were demonstrated in 50% of the TEL/AML1+ ALL; however, a cryptic t(12;21) was not detected in these cases. Hyperdiploidy of 47-48 chromosomes was encountered in 25%. Deletion of 12p resulting in the loss of the normal allele of TEL and nonspecific del(6q) were noted in 8% (1/12) and 25% (3/12) of the TEL/AML1+ children, respectively. Rapid clearance of TEL/AML1 was noted in 50% of the patients on completion of the induction therapy; however, 16.7% (2/12) TEL/AML1+ ALL relapsed at a mean of 48.6 months from diagnosis (25 months off-therapy). The incidence of relapses of TEL/AML1+ ALL was comparable to that at diagnosis in B-lineage ALL (14.3% [2/14] vs. 17.9% [12/67], p > 0.05). The relapse rate in TEL/AML1+ ALL was similar to that of TEL/AML1- ALL (16.7% [2/12] vs. 20.6% [13/63], p > 0.05). The duration of first complete remission in TEL/AML1+ ALL was significantly longer as compared to TEL/AML1- ALL (mean [range] in month: 48.6 [47.2 - 50] vs 14.6 [2.9 - 42.3], p < 0.0001). Irrespective of TEL/AML1 rearrangement, the probabilities of the five-year overall survival and the event-free survival of patients were comparable (overall survival: 100% vs. 72.3%, p = 0.166 and event-free survival: 60% vs. 56.2%, p = 0.343). Our data would not suggest a less aggressive treatment regimen for TEL/AML1+ ALL., (Copyright 2001 Wiley-Liss, Inc.)

A 15-year-old Chinese boy developed rhabdomyolysis with myoglobinuria and marked elevation of serum creatine phosphokinase following a prolonged and severe attack of asthma. He recovered after vigorous hydration and supportive treatment. Clinicians should be aware of this potentially fatal, albeit rare, complication of status asthmaticus.

Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed., Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12-year period in a university teaching hospital in Hong Kong., Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days-19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 x 109 /L and 0.06 x 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony-stimulating factor (G-CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long-term infection-related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency., Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G-CSF should be used only in those with recurrent or severe infections.