San Salvador, El Salvador
San Salvador, El Salvador

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Denburg A.E.,The Hospital for Sick Children | Joffe S.,Dana-Farber Cancer Institute | Gupta S.,The Hospital for Sick Children | Howard S.C.,St Jude Childrens Research Hospital | And 3 more authors.
Pediatric Blood and Cancer | Year: 2012

Uneven strides in research and care have led to discrepancies in childhood cancer outcomes between high and low income countries (LICs). Collaborative research may help improve outcomes in LICs by generating knowledge for local scientific communities, augmenting knowledge translation, and fostering context-specific evaluation of treatment protocols. However, the risks of such research have received little attention. This paper investigates the relationship between pediatric oncology research in LICs and four core issues in the ethics literature: standard of care, trial benefits, ethics review, and informed consent. Our aims are to highlight the importance of this field and the need for further inquiry. © 2011 Wiley Periodicals, Inc.

Marjerrison S.,The Hospital for Sick Children | Marjerrison S.,McMaster Childrens Hospital | Antillon F.,National Pediatric Oncology Unit | Bonilla M.,Benjamin Bloom National Childrens Hospital | And 7 more authors.
Pediatric Blood and Cancer | Year: 2014

Background: Relapsed childhood acute myeloid leukemia (AML) outcomes have not been documented in resource-limited settings. We examined survival after relapse for children with AML (non-APML) and acute promyelocytic leukemia (APML) in Central America. Procedure: We retrospectively evaluated outcomes of children with first relapse of AML (non-APML) and APML in Guatemala, Honduras, or El Salvador diagnosed between 1997 and 2011. Predictors of subsequent event-free survival (EFS) and overall survival (OS) were examined. Results: We identified 140 children with relapsed AML (non-APML), and 24 with relapsed APML. Two-year subsequent EFS and OS (±SE) were 7.0±2.5% and 9.1±2.8%, respectively. Worse outcomes were associated with Hispanic or Indigenous heritage, white blood cell count at diagnosis ≥50×109/L, and time to relapse <18 months. For those with relapsed APML, subsequent 2-year EFS and OS were 36.7±10.8% and 43.4±12.1%, although few patients survived beyond 3 years. 15.2% of all patients were managed solely with palliative intent following first relapse. Conclusions: Children with relapsed AML in Central America rarely survive, so palliative strategies should be considered following relapse in this population. However, children with late relapse or with APML may have a prolonged period of remission with second treatment, and consideration of re-treatment may be appropriate. Pediatr Blood Cancer 2014;61:1222-1226. © 2014 Wiley Periodicals, Inc.

Marjerrison S.,University of Toronto | Antillon F.,National Pediatric Oncology Unit | Fu L.,Hospital Escuela | Martinez R.,Hospital Mario Catarino Rivas | And 4 more authors.
Cancer | Year: 2013

Background: Outcomes for relapsed childhood acute lymphoblastic leukemia (ALL) have not been documented in resource-limited settings. This study examined survival after relapse for children with ALL in Central America. METHODS: A retrospective cohort study was performed and included children with first relapse of ALL in Guatemala, Honduras, or El Salvador between 1990 and 2011. Predictors of subsequent event-free survival (EFS) and overall survival (OS) were examined. RESULTS: There were 755 children identified with relapsed disease. The median time from diagnosis to relapse was 1.7 years (interquartile range, 0.8-3.1 years). Most relapses occurred during (53.9%) or following (24.9%) maintenance chemotherapy, and the majority occurred in the bone marrow (63.1%). Following the initial relapse, subsequent 3-year EFS (± standard error) and OS were 22.0% ± 1.7%, and 28.2% ± 1.9%, respectively. In multivariable analysis, worse postrelapse survival was associated with age ≥ 10 years, white blood cell count ≥ 50 × 109/L, and positive central nervous system status at the original ALL diagnosis, relapse that was not isolated central nervous system or testicular, and relapse < 36 months following diagnosis. Site and time to relapse were used to identify a favorable risk group whose 3-year EFS and OS were 50.0% ± 8.9% and 68.0% ± 8.1%, respectively. CONCLUSIONS: Prognosis after relapsed ALL in Central America is poor, but a substantial number of those with favorable risk features have prolonged survival, despite lack of access to stem cell transplantation. Stratification by risk factors can guide therapeutic decision-making. Cancer 2013. © 2012 American Cancer Society.

Gupta S.,University of Toronto | Bonilla M.,Benjamin Bloom National Childrens Hospital | Gamero M.,Benjamin Bloom National Childrens Hospital | Fuentes S.L.,Benjamin Bloom National Childrens Hospital | And 2 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2011

BACKGROUND: Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. METHODS: We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. RESULTS: Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. CONCLUSIONS: In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions. Copyright © 2011 by Lippincott Williams & Wilkins.

Friedrich P.,Dana Farber Boston Childrens Cancer and Blood Disorders Center | Ortiz R.,La Mascota Childrens Hospital | Fuentes S.,Benjamin Bloom National Childrens Hospital | Gamboa Y.,National Childrens Hospital | And 6 more authors.
Cancer | Year: 2014

BACKGROUND The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs. METHODS An ecologic model centered on pediatric sarcoma and expanded to country as the environment was used as a benchmark for studying the delivery of solid tumor care in MICs. Data on resources were gathered from 7 centers that were members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data were available, were retrieved from hospital-based cancer registries for 6 of the 7 centers, and were analyzed by country. Patients who were diagnosed from January 1, 2000 to December 31, 2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. To explore correlations between resources and outcomes, a pilot performance index was created. RESULTS The analyses identified specific deficits in human resources, communication, quality, and infrastructure. The treatment abandonment rate, the proportion of metastatic disease at diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from 15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment abandonment rate correlated inversely with health economic expenditure per capita (r = -0.86; P =.03) and life expectancy at birth (r = -0.93; P =.007). The 4-year AOS rate correlated inversely with the mortality rate among children aged <5 years (r = -0.80; P = 0.05) and correlated directly with the pilot performance index (r = 0.98; P = 0.005). CONCLUSIONS Initiatives to improve the effectiveness of treatment for pediatric solid tumors in MICs are warranted, particularly for pediatric sarcomas. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive, multidisciplinary teams are identified as keystones in Central America. A measure that meaningfully describes performance in delivering pediatric cancer care is feasible and needed to advance comparative, prospective analysis of pediatric cancer care and to define resource clusters internationally. Cancer 2014;120:112-125. © 2013 American Cancer Society. Effective delivery of pediatric solid tumor care poses a challenge to centers in low-income and middle-income countries. However, the complex variety of factors involved in delivery of care can be conceptualized in discrete components, analyzed using transparent methods, and interpreted in ways meaningful to leadership at a pediatric cancer center. © 2013 American Cancer Society.

Gupta S.,University of Toronto | Antillon F.A.,National Pediatric Oncology Unit | Bonilla M.,Benjamin Bloom National Childrens Hospital | Fu L.,Hospital Escuela | And 3 more authors.
Cancer | Year: 2011

BACKGROUND: The objectives of this study were to describe the incidence, timing, and predictors of treatment-related mortality (TRM) among children with acute lymphoblastic leukemia (ALL) in El Salvador, Guatemala, and Honduras. METHODS: Patients aged <20 years who were diagnosed with ALL between January 2000 and March 2008, who received treatment in any of the 3 countries, and who started induction chemotherapy were included in the study. Almost all patients were treated on the El Salvador-Guatemala-Honduras II protocol, which was based on the St. Jude Total XIII and XV protocols. Biologic, socioeconomic, and nutritional variables were examined as predictors of TRM. RESULTS: Of 1670 patients, TRM occurred as a first event in 156 children (9.3%); TRM occurred during remission induction therapy in 92 of 156 children (59%), between remission induction and maintenance therapy in 27 of 156 children (17%), and during maintenance therapy in 37 of 156 children (24%). Although the TRM rate decreased in patients who were diagnosed after July 1, 2004 (11.2% vs 7.9%; P =.02), the rate of induction death did not change (5.2% vs 5.8%; P =.58). Independent predictors of induction death included higher risk ALL (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.03-3.27; P =.04), lower initial platelet counts (OR per 10 × 109/L, 0.94; 95% CI, 0.89-0.98; P =.005), and longer travel time to the clinic (OR, 1.06 per hour; 95% CI, 1.01-1.14; P =.03). CONCLUSIONS: In Central America, TRM remains an important cause of treatment failure in children with ALL. A large proportion of TRM occurs in maintenance, although this proportion has decreased over time. Supportive care interventions should especially target children who present with low platelet counts. Further study on transfusion ability and the location of induction deaths is required. Cancer 2011;. © 2011 American Cancer Society. Rates of treatment-related mortality (TRM) were significantly higher in patients with acute lymphoblastic leukemia (ALL) in low-income countries compared with similar patients in high-income countries. In a cohort of children with ALL across 3 Central American countries, the authors observed that the timing, causes, and predictors of TRM were different in this population than in high-income settings, suggesting that different interventions are required to improve outcomes. Copyright © 2011 American Cancer Society.

PubMed | Columbia University, Benjamin Bloom National Childrens Hospital, National Pediatric Oncology Unit, Harvard University and St Jude Childrens Research Hospital
Type: Journal Article | Journal: Pediatric blood & cancer | Year: 2016

Global variations in the incidence of pediatric cancers have been described; however, the causes of such differences are not known. We investigated the relationship between the incidence of embryonal tumors and human development index on a global scale. Increasing incidence of neuroblastoma correlates significantly with an increasing index of human development, with greater incidence among countries with high socioeconomic development, in apparent contrast to the incidence of retinoblastoma. While more data are needed to corroborate this observation, our findings suggest new avenues for etiological research and serve as a call for support of population-based cancer registries in low-middle-income countries.

Friedrich P.,Dana Farber Childrens Hospital Cancer Center | Ortiz R.,La Mascota Childrens Hospital | Strait K.,Dana Farber Childrens Hospital Cancer Center | Fuentes S.,Benjamin Bloom National Childrens Hospital | And 7 more authors.
Cancer | Year: 2013

Background: Children with cancer in middle-income countries have inferior outcomes compared with similar children in high-income countries. The magnitude and drivers of this survival gap are not well understood. In the current report, the authors sought to describe patterns of clinical presentation, magnitude of treatment abandonment, and survival in children with sarcoma in Central America. METHODS: A retrospective review was conducted of hospital-based registries from national pediatric oncology referral centers. Patients with newly diagnosed osteosarcoma, Ewing sarcoma, rhabdomyosarcoma (RMS), and soft tissue sarcoma (STS) between January 1, 2000 and December 31, 2009 were included. Survival analyses were performed first using standard definitions of overall survival (OS) and event-free survival (EFS) and then with abandonment included as an event (abandonment-sensitive OS and abandonment-sensitive EFS). RESULTS: In total, 785 new cases of pediatric sarcoma were reported (264 diagnoses of osteosarcoma, 175 diagnoses of Ewing sarcoma, 240 diagnoses of RMS, and 106 diagnoses of STS). The rate of metastatic disease at presentation was high (osteosarcoma, 38%; Ewing sarcoma, 39%; RMS, 29%; and STS, 21%). The treatment abandonment rate also was high, particularly among patients with extremity bone sarcomas (osteosarcoma, 30%; Ewing sarcoma, 15%; RMS, 25%; and STS, 15%). Of 559 patients who experienced a first event, 59% had either recurrent or progressive disease. The 4-year OS rate (±standard error) was 40% ± 3%, and the EFS rate was 30% ± 2%; however, these rates decreased further to 31% ± 2% and 24% ± 2%, respectively, when abandonment was taken into account. CONCLUSIONS: The current results indicated that high rates of metastases and treatment abandonment and difficulty with upfront treatment effectiveness are important contributors to the poor survival of children with pediatric sarcomas in Central America. Initiatives for early diagnosis, psychosocial support, quality improvement, and multidisciplinary care are warranted to improve outcomes. © 2012 American Cancer Society.

Gavidia R.,Benjamin Bloom National Childrens Hospital | Fuentes S.L.,Benjamin Bloom National Childrens Hospital | Vasquez R.,Benjamin Bloom National Childrens Hospital | Bonilla M.,Benjamin Bloom National Childrens Hospital | And 7 more authors.
PLoS ONE | Year: 2012

Background: Infection remains the most common cause of death from toxicity in children with cancer in low- and middle-income countries. Rapid administration of antibiotics when fever develops can prevent progression to sepsis and shock, and serves as an important indicator of the quality of care in children with acute lymphoblastic leukemia and acute myeloid leukemia. We analyzed factors associated with (1) Longer times from fever onset to hospital presentation/antibiotic treatment and (2) Sepsis and infection-related mortality. Method: This prospective cohort study included children aged 0-16 years with newly diagnosed acute leukemia treated at Benjamin Bloom Hospital, San Salvador. We interviewed parents/caregivers within one month of diagnosis and at the onset of each new febrile episode. Times from initial fever to first antibiotic administration and occurrence of sepsis and infection-related mortality were documented. Findings: Of 251 children enrolled, 215 had acute lymphoblastic leukemia (85.7%). Among 269 outpatient febrile episodes, median times from fever to deciding to seek medical care was 10.0 hours (interquartile range [IQR] 5.0-20.0), and from decision to seek care to first hospital visit was 1.8 hours (IQR 1.0-3.0). Forty-seven (17.5%) patients developed sepsis and 7 (2.6%) died of infection. Maternal illiteracy was associated with longer time from fever to decision to seek care (P = 0.029) and sepsis (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.09-8.63; P = 0.034). More infectious deaths occurred in those with longer travel time to hospital (OR 1.36, 95% CI 1.03-1.81; P = 0.031) and in families with an annual household income

Bonilla M.,Benjamin Bloom National Childrens Hospital | Gupta S.,University of Toronto | Vasquez R.,Benjamin Bloom National Childrens Hospital | Fuentes S.L.,Benjamin Bloom National Childrens Hospital | And 3 more authors.
European Journal of Cancer | Year: 2010

Background: Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. Methods: We describe predictors of survival for children in El Salvador with ALL. We included patients <16 years diagnosed with ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). Results: 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P = 0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10 × 109/L = 1.03, 95% CI 1.02-1.05; P < 0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. Conclusion: Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies. © 2010 Elsevier Ltd. All rights reserved.

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