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Lillian Sung

Publications and source records attributed to Lillian Sung.

32 records · Page 2Linked to original sources
PubMed2004

A multiagent strategy to decrease regimen-related toxicity in children undergoing allogeneic hematopoietic stem cell transplantation.

Regimen-related toxicity (RRT) is a frequent cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this pilot study, we examined the feasibility and potential efficacy of administering a fixed combination of agents as a novel approach to reducing RRT in children undergoing HSCT. Thirty-seven patients were treated with ursodeoxycholic acid, folinic acid, vitamin E, and parenteral nutrition titrated to measured energy expenditure in the peritransplantation period. Outcomes were compared with those in historical controls (n = 131). Compliance with oral ursodeoxycholic acid and vitamin E of at least 90% was achieved in a mean of 86% (95% confidence interval, 75%-97%) of patients. In the study group, we observed (1) reduced prevalence and severity of mucositis (P = .008 and.004, respectively); (2) less severe hepatic toxicity (P = .007); and (3) shorter time to engraftment (P = .02) compared with the control group. These benefits appeared most pronounced among high-risk patients. The administration of this regimen, including oral medications, is feasible during the peritransplantation period, and it is well tolerated. The decreased RRT observed in comparison to historical controls suggests that combination approaches deserve exploration as a means of reducing the morbidity of HSCT.

Adolescent↗
PubMed2004

Late events occurring five years or more after successful therapy for childhood rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

The aim of our study was to describe late failures in children who initially survived event-free five years from a diagnosis of rhabdomyosarcoma. Charts of children enrolled in the Intergroup Rhabdomyosarcoma Study Group (IRSG) trials III, IV pilot and IV (1984-1997) who survived five years event-free and subsequently experienced an adverse event (disease recurrence, second malignant neoplasm or death from other causes) were reviewed. Of the 2534 enrolled patients, 1160 were event-free at five years and 48 subsequently experienced a late event. The estimated 10-year event rate for the 1160 patients who were alive and event-free at five years was 9% (95% Confidence Interval (CI) 5%, 13%). Patients with both advanced disease (Group III/IV) and large primary tumours at diagnosis (> 5 cm) were at the highest risk for late events (19%; 95% CI 8%, 30%). Late events after successful treatment for rhabdomyosarcoma occur in 9%. Those with advanced disease and large primary tumours have the highest risk of late events.

Adolescent↗
PubMed2004

Update on childhood neutropenia: molecular and clinical advances.

Congenital and inherited disorders are important differential diagnoses of neutropenia, particularly in neonates and children, although acquired causes are more common. This article focuses on recent advances in understanding the cellular and molecular defects in inherited neutropenias as well as issues that are related to clinical presentation, diagnosis, and complications.

Child↗
PubMed2004

Effect of intracranial bleeds on the health and quality of life of boys with hemophilia.

OBJECTIVES: To compare the health, physical function, and quality of life (QoL) of boys with hemophilia with and without a history of intracranial hemorrhage (ICH). STUDY DESIGN: Of 172 patients with hemophilia A or B, 18 (10%) had at least one episode of ICH. For outcome assessments, 16 of 18 (89%) boys with ICH and 32 controls, matched (1:2) for age and severity of hemophilia, were available. The outcome measures were neurologic function, physical function, and QoL. RESULTS: The median age of the boys at the first ICH was 5.9 months (range, 1 day to 2.7 years). Boys with ICH had a higher incidence of inhibitors and lower mean household income. Neurologic examination was abnormal in seven of 16 (44%) boys with ICH and nine of 32 (28%) controls (P=.3). The mean physical function in boys with ICH was lower (82%+/-25%) compared with controls (93.5%+/-12%, P=.045). The QoL was decreased in boys with ICH compared with controls (6.8+/-3.2 vs 8.5+/-1.4, P=.02), whereas health-related QoL was not significantly different between groups. CONCLUSION: The poorer long-term outcomes of boys with hemophilia appropriately treated for ICH, especially in the domain of QoL, suggest that new strategies to prevent ICH and to manage ICH effectively in this population are needed.

Adolescent↗
PubMed2004

Hemophagocytic lymphohistiocytosis in children: abdominal US findings within 1 week of presentation.

PURPOSE: To evaluate the ultrasonographic (US) findings at presentation in a series of children who received a diagnosis of hemophagocytic lymphohistiocytosis (HLH) at a single institution. MATERIALS AND METHODS: All available results of imaging studies of children who received a diagnosis of HLH between January 1985 and June 2000 were retrieved. For nine patients, abdominal US images obtained within 1 week of presentation to the hospital were reviewed retrospectively by two radiologists who were aware of the diagnosis and of the original interpretation of each study. US images were examined for evidence of splenomegaly, hepatomegaly, ascites, gallbladder wall thickening, increased periportal echogenicity, lymphadenopathy, pleural effusion, and nephromegaly. Any other abnormalities were also recorded. Differences in interpretation were resolved by consensus. The patients ranged in age from 2 months to 4(1/2) years. The male-to-female ratio was 5:4. RESULTS: Findings at presentation included splenomegaly (in eight of the nine children), hepatomegaly (in seven children), ascites (in six children), gallbladder wall thickening (in six children), increased periportal echogenicity (in three children), lymphadenopathy (in three children), and pleural effusion (in two children). Miscellaneous findings in individual patients included coarse hepatic echotexture with a single 9-mm hypoechoic focus in the liver, multiple hypoechoic foci in the spleen, nephromegaly, gallstone, increased renal cortical echogenicity, and mural thickening of the duodenum. CONCLUSION: In the appropriate clinical setting, the differential diagnosis of a combination of hepatosplenomegaly, ascites, gallbladder wall thickening, increased periportal echogenicity, lymphadenopathy, and/or pleural effusion should include HLH.

Abdomen↗
PubMed2004

Tobramycin pharmacokinetics in children with febrile neutropenia undergoing stem cell transplantation: once-daily versus thrice-daily administration.

STUDY OBJECTIVE: To describe the pharmacokinetic disposition of tobramycin in children undergoing stem cell transplantation (SCT) after intravenous administration either every 24 hours or every 8 hours, and to use this information to create initial dosing guidelines for administration every 24 hours in this patient population. DESIGN: Pharmacokinetic analysis of a randomized controlled trial. SETTING: The Hospital for Sick Children, Toronto, Ontario, Canada. PATIENTS: Sixty children (< 18 yrs) with febrile neutropenia undergoing stem cell transplantation. INTERVENTION: Patients were randomized to receive intravenous tobramycin either every 24 hours (29 patients) or every 8 hours (31 patients). Initially, they received either 2.5 mg/kg/dose every 8 hours or weight-based doses by age group (< 5 yrs, 9 mg/kg/dose; 5 to < 12 yrs, 8 mg/kg/dose; > or = 12 yrs, 7 mg/kg/dose) every 24 hours. MEASUREMENTS AND MAIN RESULTS: Serum tobramycin concentrations were obtained at 2 and 8 hours after the first dose. Initial guidelines for dosing every 24 hours were derived using the parameters from all patients to achieve a maximum serum concentration (Cmax) of 20-22.5 mg/L and a drug-free interval (time during dosing interval when the tobramycin concentration was < 1 mg/L) of at least 4 hours. After the first tobramycin dose, the elimination rate constant (kel) and volume of distribution (Vd) observed in the every-8-hour group (23 patients) were 0.34 +/- 0.09 hours(-1) and 0.48 +/- 0.21 L/kg, respectively. The kel and Vd in the every-24-hour group (22 patients) were 0.43 +/- 0.12 hr(-1) and 0.43 +/- 0.26 L/kg, respectively. Tobramycin Vd varied with age. Initial doses of tobramycin every 24 hours recommended to achieve the target parameters are 10 mg/kg/dose for patients aged 6 months to less than 9 years, 8 mg/kg/dose for those aged 9 to less than 12 years, and 6 mg/kg/dose for those aged 12 years or older. CONCLUSION: Children undergoing SCT who receive tobramycin every 24 hours should receive an initial dose based on age. Further validation of the proposed dosing guidelines is required.

Adolescent↗
PubMed2003

Randomized controlled trial of once- versus thrice-daily tobramycin in febrile neutropenic children undergoing stem cell transplantation.

BACKGROUND: The benefits of aminoglycoside antibiotics, such as tobramycin, administered as a once-daily dose to manage febrile neutropenia, have been demonstrated in many patient populations. However, toxicity and safety data are lacking for pediatric stem cell transplant recipients, who are at especially high risk for aminoglycoside-related toxicity and infectious morbidity. In particular, the relative nephrotoxicity and efficacy of tobramycin administered as a single daily dose or as three daily doses among this patient population is not known. METHODS: We conducted a randomized, double-blind controlled study of tobramycin dosing among children 18 years or younger who had fever and neutropenia while undergoing stem cell transplantation. From October 2000 through November 2002, 60 children were randomly assigned to receive intravenous tobramycin, as either a single daily dose (n = 29) or every 8 hours (n = 31), in combination with either piperacillin or ceftazidime (intravenous). Tobramycin doses were adjusted to achieve pharmacokinetic targets. The primary outcome was nephrotoxicity, as represented by the maximal percent increase in serum creatinine concentration throughout the episode of febrile neutropenia relative to the baseline serum creatinine concentration. Efficacy was a secondary outcome and was defined as survival of the episode without modification of the antibacterial regimen. All statistical tests were two-sided. RESULTS: In a modified intent-to-treat analysis, the mean maximal percent increase in serum creatinine concentration was 32% (N = 26) in the once daily dose group and 51% (N = 28) in the every 8 hours dose group (difference = 19%, 95% confidence interval [CI] = 0% to 38%; P =.054). Among patients evaluable for efficacy, 12 (46%) of 26 patients in the once daily dose group and five (19%) of 27 patients in the every 8 hours dose group survived the episode of febrile neutropenia without requiring antibacterial treatment modification (difference = 27%, 95% CI = 4% to 52%; P =.03). There was one death in each group. CONCLUSIONS: In febrile neutropenic children undergoing stem cell transplantation, tobramycin may be less nephrotoxic and more efficacious when administered as a once daily dose than when administered every 8 hours.

Adolescent↗
PubMed2003

Treatment options for patients with acute myeloid leukemia with a matched sibling donor: a decision analysis.

BACKGROUND: The role of allogeneic bone marrow transplantation (BMT) in the consolidation of young adults with acute myeloid leukemia (AML) with matched sibling donors (MSD) is controversial. Although BMT is associated with increased event free survival compared with intensive chemotherapy (CT) consolidation, BMT also is associated with increased treatment-related mortality and likely decreased quality of life and life expectancy in patients who do not develop recurrent disease. METHODS: The authors used decision analysis to compare three strategies for maximizing quality-adjusted life years (QALYs) in patients with AML in first remission with an MSD: BMT All, BMT None (consolidation CT only), or BMT in high-risk patients, as defined by baseline cytogenetic testing (Test strategy). A second decision-analysis tree was then constructed that compared BMT with CT specifically for patients with intermediate cytogenetics. RESULTS: Using expected QALYs as the outcome measure, the Test, BMT All, and BMT None strategies were associated with 20.10 QALYs, 19.63 QALYs, and 18.38 QALYs, respectively. Thus, the Test strategy, with CT for low-risk patients and BMT for intermediate risk and high-risk patients, was expected to be the optimal strategy. In the intermediate cytogenetic decision analysis, although the expected QALY for BMT recipients was higher compared with CT recipients (19.78 QALYs vs. 18.75 QALYs), because of uncertainty in variable estimates, the optimal choice was less clear. CONCLUSIONS: CT consolidation is a reasonable option for patients with AML who have favorable cytogenetics, even if an MSD is available. This model provides a framework from which patients with AML and their physicians can make decisions about consolidation therapy.

Acute Disease↗
PubMed2003

Folic acid food fortification is associated with a decline in neuroblastoma.

BACKGROUND: Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known. METHODS: We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification. RESULTS: An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89). CONCLUSIONS: Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.

Canada↗
PubMed2003

Vitamin E: the evidence for multiple roles in cancer.

There is accumulating evidence that vitamin E may have different roles in the prevention and treatment of cancer. The purpose of this review is to summarize and evaluate this evidence and to suggest future avenues of research. A comprehensive literature review of vitamin E and cancer was conducted. Articles were organized into the following categories: 1) cancer prevention, 2) direct antineoplastic activity, 3) augmentation of chemotherapy effects, and 4) attenuation or treatment of chemotherapy toxicity. The evidence was systematically evaluated using guidelines developed by the U.S. Preventative Services Task Force. There is evidence to suggest that those individuals with higher serum vitamin E levels and those receiving vitamin E supplementation have a decreased risk of some cancers, including lung, prostate, stomach, and gastrointestinal carcinoma. However, these results differed depending on the study design and the population studied. There is insufficient evidence to support anticancer activity and attenuation of chemotherapy toxicity by vitamin E. Vitamin E is likely to be important in the prevention of some cancers. The therapeutic role of vitamin E is poorly understood. Further research will be required before routine use of vitamin E in patients with cancer can be advocated in the clinical setting.

Case-Control Studies↗
PubMed2002

Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss.

Our inability to purify hematopoietic stem cells (HSCs) precludes direct study of many aspects of their behavior in the clinical hematopoietic stem cell transplantation (HSCT) setting. We indirectly assessed stem/progenitor cell behavior in the first year after HSCT by examining changes in neutrophil telomere length, X-inactivation ratios, and cycling of marrow progenitors in 25 fully engrafted allogeneic HSCT recipients. Donors were sampled once and recipients at engraftment and 2 to 6 months and 12 months after HSCT. Telomere length was measured by an in-gel hybridization technique, X-inactivation ratios were measured by the human androgen receptor assay, and cell cycle status was determined by flow cytometric analysis of pyronin Y- and Hoechst 33342-stained CD34(+)CD90(+) and CD34(+)CD90(-) marrow cells. Compared with their donors, recipients' telomeres were shortened at engraftment (-424 base pairs [bp]; P <.0001), 6 months (-495 bp; P =.0001) after HSCT, and 12 months after HSCT (-565 bp; P <.0001). There was no consistent pattern of change in telomere length from 1 to 12 months after HSCT; marked, seemingly random, fluctuations were common. In 11 of 11 informative recipients, donor X-inactivation ratios were faithfully reproduced and maintained. The proportion of CD34(+)CD90(+) progenitors in S/G(2)/M was 4.3% in donors, 15.7% at 2 to 6 months (P <.0001) after HSCT, and 11.5% at 12 months after HSCT (P <.0001, versus donors; P =.04, versus 2-6 months). Cycling of CD34(+) CD90(-) progenitors was largely unchanged. We infer that (1) HSCT-induced accelerated telomere loss is temporary and unlikely to promote graft failure or clonal hematopoietic disorders and (2) the striking fluctuations in telomere length and variation in pattern of telomere loss reflect stochastic determination of HSC fate after HSCT.

Adult↗
PubMed2002

Adverse outcomes in primary hemophagocytic lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by abnormal proliferation of macrophages. Although the mortality rate in children diagnosed with primary HLH is high, little has been described about the nature of adverse events. This review evaluates unfavorable events in children with primary HLH to suggest methods of improving outcomes. METHODS: Charts of patients who met diagnostic criteria for primary HLH at the Hospital for Sick Children between January 1985 and June 2000 were retrospectively reviewed. The primary outcome measure was an adverse event, defined as death, the subsequent diagnosis of malignancy, or developmental delay. RESULTS: Twenty children were diagnosed with primary HLH. The median age at diagnosis was 6.5 months (range 1-78 months). Nineteen children received chemotherapy and two underwent matched sibling donor bone marrow transplantation. Of the 20 children, 12 (60%) died. These deaths were attributed to progressive HLH in 4 cases and invasive infection in 8 cases. These infections consisted of disseminated cytomegalovirus infection (n = 1), sepsis (n = 1), and invasive fungal infections (n = 6). Eight children survived. Two were subsequently diagnosed with malignancy. Two others were found to have significant developmental delay. CONCLUSIONS: The overall mortality rate was 60% in our series of 20 children with primary HLH; 50% of deaths were directly attributable to invasive fungal infection. Developmental delay and the diagnosis of malignancy are important events in this cohort.

Cerebrospinal Fluid↗
PubMedDate not supplied

Tumor necrosis in pediatric osteosarcoma: impact of modern therapies.

Tumor necrosis following preoperative chemotherapy in patients with osteosarcoma is a predictor of overall survival. With modern therapies, 45% of patients are expected to achieve more than 90% tumor necrosis. Investigators at the authors' center, however, increasingly noted that patients were experiencing inferior necrosis responses. A retrospective study of treated patients at the center was undertaken to examine this. The purpose of this study was to determine (1) whether the number of patients with favorable histological responses had changed over time and (2) whether the percentage of patients with favorable responses was similar to published outcomes. Chart reviews were performed on patients treated from 1993 to 2003 according to the Pediatric Oncology Group 9351, regimen A protocol. Twenty-one patients met all eligibility requirements; 52% of patients had more than 90% necrosis. No correlation existed between degree of necrosis and year of treatment (r = 0.06; P = .8). Patients with osteosarcoma treated at the authors' institution have comparable tumor necrosis responses to published outcomes, and no change occurred over time. This study stresses the importance of rigorous retrospective reviews before implementing treatment changes.

Adolescent↗