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ABSTRACT: 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 × 10(9) /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 2012. © 2012 American Cancer Society.
Cancer 11/2012; · 4.77 Impact Factor
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ABSTRACT: 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.
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.
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 <US$2,000 (OR 13.90, 95% CI 1.62-119.10; P = 0.016).
Illiteracy, poverty, and longer travel times are associated with delays in assessment and treatment of fever and with sepsis and infectious mortality in pediatric leukemia. Providing additional education to high-risk families and staying at a nearby guest house during periods of neutropenia may decrease sepsis and infectious mortality.
PLoS ONE 01/2012; 7(8):e43639. · 4.09 Impact Factor
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ABSTRACT: Cure rates in paediatric acute myeloid leukaemia in low-income countries lag behind those in high-income countries, in part secondary to higher rates of treatment-related mortality. Patterns of treatment-related mortality are likely to differ between low and high-income centres. Understanding low-income setting patterns is necessary before effective interventions aimed at decreasing treatment-related mortality can be designed. Our aim was to describe the incidence, timing and predictors of treatment-related mortality among Central American children with acute myeloid leukaemia.
We evaluated patients younger than 21 years diagnosed with acute myeloid leukaemia from 2000 to 2008 in El Salvador, Honduras or Guatemala. Biologic, socioeconomic and nutritional variables collected prospectively were examined as potential predictors of treatment-related mortality.
Among 279 patients, treatment-related mortality occurred in 65 (23%). Of 65 deaths, 51 (78.5%) occurred before or during induction, resulting in an early death rate of 18.3%. The most common causes of treatment-related mortality were infection (29/65; 45%) and haemorrhage (13/65; 20%). Infection accounted for 33% of treatment-related mortality before remission induction therapy versus 40% during induction and 77% after induction (P = 0.03). Rates of treatment-related mortality did not vary between time periods 1 and 2 (24.8% versus 21.4%; P = 0.32). Only lower initial platelet count predicted early death (odds ratio per 10 × 10(9)/L = 0.88, 95% Confidence Interval (CI) 0.79-0.97; P < 0.001).
Treatment-related mortality remains a significant cause of treatment failure. Supportive care interventions are needed. Children presenting with low initial platelet counts were at highest risk of induction death, suggesting that transfusion practices should be evaluated.
European journal of cancer (Oxford, England: 1990) 11/2011; 48(9):1363-9. · 4.12 Impact Factor
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ABSTRACT: Retinoblastoma is highly curable in high income countries. Low income countries have poor results due to advanced disease and lack of resources. Central American Association of Pediatric Hematology Oncology (AHOPCA) aimed to standardize the approach and to improve outcomes of patients with retinoblastoma.
One hundred seventy-one patients, age <18 years newly diagnosed with retinoblastoma were treated according to laterality and stage. Therapeutic modalities were: surgery (enucleation), local control (laser therapy, cryotherapy), chemotherapy, and radiation therapy. Chemotherapy consisted of vincristine, etoposide, and carboplatin (6 cycles). Outcomes were measured by overall survival. Events were abandonment of therapy and death.
One hundred seventy-one patients (129 unilateral, 42 bilateral) were treated. Median age was 2 years 4 months; 112 (66%) were diagnosed before 3 years of age. 119 (92%) eyes in patients with unilateral disease were Reese-Ellsworth IV or V versus 52 (62%) eyes in patients with bilateral disease. Extraocular disease was more prevalent in unilateral disease (65% vs. 50%). Older age at diagnosis correlated with higher stage. Estimated overall survival at 60 months was 0.48 ± 0.04. Outcome of patients with bilateral disease was significantly better than unilateral (62% ± 0.09 vs. 42% ± 0.05, P = 0.0006). Thirty-eight patients (22%) refused or abandoned therapy.
Protocol-directed therapy for retinoblastoma in Central America is possible. Patients present with advanced disease and outcome is significantly worse than in middle and high-income countries. Refusal and abandonment of therapy are societal events that affect outcome. Initiatives aimed at improving early diagnosis, while dedicated treatment centers are developed, are critical.
Pediatric Blood & Cancer 09/2011; 58(4):545-50. · 1.89 Impact Factor
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Alessandra Sala,
Emanuela Rossi,
Federico Antillon,
Ana Lucia Molina,
Tania de Maselli, Miguel Bonilla,
Angelica Hernandez,
Roberta Ortiz,
Carlos Pacheco,
Rosa Nieves,
Marta Navarrete,
Max Barrantes,
Paul Pencharz,
Maria Grazia Valsecchi,
Ronald Barr
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ABSTRACT: The prevalence of malnutrition in children may exceed 50% in countries with limited resources. The aims of this study were to assess nutritional status at diagnosis in children and adolescents with cancer, and to correlate it with clinical outcomes in the Spanish speaking countries of Central America that formed the AHOPCA (Asociacion de Hemato-Oncologia Pediatrica de Centro America) consortium.
Patients aged 1-18 years, diagnosed with cancer between 1st October 2004 and 30th September 2007, were eligible for study. Weight (kg) and height or length (m), mid upper arm circumference--MUAC and triceps skin fold thickness--TSFT were measured and their Z-scores or percentiles were calculated. Three categories of nutritional status were defined according to these parameters.
A total of 2954 new patients were enrolled; 1787 had all anthropometric measurements performed and 1513 also had measurements of serum albumin. By arm anthropometry 322/1787 patients (18%) had moderate nutritional depletion and 813/1787 patients (45%) were severely depleted. Adding serum albumin, the proportion classified as severely depleted rose to 59%. Malnourished children more often abandoned therapy and their event free survival was inferior to that of other children.
Arm anthropometry in children with cancer is a sensitive measure of nutritional status. Since malnutrition at diagnosis was related to important clinical outcomes, an opportunity exists to devise simple, cost-effective nutritional interventions in such children that may enhance their prospects for survival.
European journal of cancer (Oxford, England: 1990) 07/2011; 48(2):243-52. · 4.12 Impact Factor
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ABSTRACT: 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.
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.
Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 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.
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.
Journal of Pediatric Hematology/Oncology 05/2011; 33(4):276-80. · 1.16 Impact Factor
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ABSTRACT: 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.
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.
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 × 10(9) /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).
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.
Cancer 03/2011; 117(20):4788-95. · 4.77 Impact Factor
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ABSTRACT: 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.
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).
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 10×10(9)/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.
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.
European journal of cancer (Oxford, England: 1990) 12/2010; 46(18):3280-6. · 4.12 Impact Factor
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ABSTRACT: Abandonment of therapy is one of the most common causes of treatment failure among children with cancer in low-income countries. Our objectives were to describe the prevalence and predictors of abandonment among such children with cancer in El Salvador. We analyzed data on patients younger than 16 years, diagnosed with any malignancy between January 2001 and December 2003 at the Benjamin Bloom National Children's Hospital, San Salvador. Among 612 patients, 353 were male (58%); the median age at diagnosis was 5.1 years; 59% of patients were diagnosed with leukemia/lymphoma, 28% with solid tumors and 13% with brain tumors. The prevalence of abandonment was 13%. Median time to abandonment was 2.0 (range 0-36) months. In univariate analyses, paternal illiteracy [odds ratio (OR) 3.8, 95% confidence interval (CI) 2.0-7.2; p = 0.001]; maternal illiteracy (OR = 5.1, 95% CI 2.5-10; p < 0.0001); increasing number of household members (OR = 1.2, 95% CI 1.1-1.3; p = 0.004); and low monthly household income (OR per $100 = 0.59, 95% CI 0.45-0.75; p < 0.0001) all significantly increased the risk of abandonment, whereas travel time to hospital did not. In multiple regression analyses, low monthly income and increased number of people in the household were independently predictive of abandonment. In conclusion, in El Salvador, despite the provision of free treatment, socioeconomic variables significantly predict increased risk of abandonment of therapy. Understanding the pathways through which socioeconomic status affects abandonment may allow the design of effective interventions.
International Journal of Cancer 05/2009; 125(9):2144-6. · 5.44 Impact Factor
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Judith A Wilimas,
Matthew W Wilson,
Barrett G Haik,
Margarita Barnoya,
Ligia Fu,
Mauricio Castellanos, Miguel Bonilla,
Blanca Phillips,
Eugene M Helveston,
Sandra Luna-Fineman,
Raul Ribeiro,
Carlos Rodriguez-Galindo
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ABSTRACT: Retinoblastoma, a curable eye tumor, is associated with poor survival in Central America (CA). To develop a retinoblastoma program in El Salvador, Guatemala, and Honduras, twinning initiatives were undertaken between local pediatric oncology centers, nonprofit foundations, St. Jude Children's Research Hospital, and the University of Tennessee Hamilton Eye Institute.
The retinoblastoma program focused on developing early diagnosis programs in Honduras with national vaccination campaigns, developing treatment protocols suited to local conditions, building local networks of oncologists and ophthalmologists, training local healthcare providers, using modern donated equipment for diagnosis and treatment, and the ORBIS Cybersight consultation program and Internet meetings to further education and share expertise. Pediatric ophthalmologists and oncologists worked with foundations to treat patients locally with donated equipment and Internet consultations, or at the center in Guatemala.
Number of patients successfully treated increased after the program was introduced. For 2000-2003 and 2004-2007, patients abandoning/refusing treatment decreased in Guatemala from 20 of 95 (21%) to 14 of 123 (11%) and in Honduras from 13 of 37 (35%) to 7 of 37 (19%). Survival in El Salvador was good and abandonment/refusal low for both periods. Of 18 patients receiving focal therapy for advanced disease, 14 have single remaining eyes.
Development of the program in CA has decreased abandonment/refusal and enabled ophthalmologists at local centers to use modern equipment to provide better treatment. This approach might serve as a guide for developing other multispecialty programs.
Pediatric Blood & Cancer 04/2009; 53(1):42-6. · 1.89 Impact Factor
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Scott C Howard,
Marco Marinoni,
Luis Castillo, Miguel Bonilla,
Gianni Tognoni,
Sandra Luna-Fineman,
Federico Antillon,
Maria Grazia Valsecchi,
Ching-Hon Pui,
Raul C Ribeiro,
Alessandra Sala,
Ronald D Barr,
Giuseppe Masera
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ABSTRACT: The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.
Pediatric Blood & Cancer 04/2007; 48(3):364-9. · 1.89 Impact Factor
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ABSTRACT: Cancer is the commonest cause of disease-related death in children over 5 years of age in various parts of Latin America, but the survival rates are improving. This study assessed the health status and health-related quality of life (HRQL) of more than 200 survivors of cancer in childhood in the countries of a Central American consortium devoted to pediatric hematology-oncology. Patients' self-reports and parental proxy assessments were collected using interviewer-administered Spanish-language questionnaires, and physicians provided assessments using self-complete questionnaires, based on the complementary Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems. Inter-rater agreement, measured by intra-class correlation (ICC), was fair to moderate (0.34<ICC<0.55) between patients, parents, and physicians for HRQL scores. There was substantial or almost perfect agreement (ICC>0.60) for all 3 pairs of assessors for readily assessable attributes: HUI2 sensation, HUI3 vision, HUI3 hearing, and HUI3 ambulation. Less than 40% of the patients reported being in perfect health. More than 20% reported being in health states with HRQL scores corresponding to moderate or severe disability, notably in the attributes of emotion and cognition. The results reflect a common profile in survivors of cancer in childhood, including those from industrialized societies. This study illustrates the feasibility of collecting reliable and valid information on HRQL in the developing country context, raising the prospect that such information could be used to influence clinical practice.
Journal of Pediatric Hematology/Oncology 07/2006; 28(6):331-41. · 1.16 Impact Factor
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ABSTRACT: Purpose: To investigate the relationship between survival and malnutrition at the time of diagnosis among children treated for cancer in two developing countries.
Patients and Methods: We studied 443 children treated for cancer between 1995 and 1998 at two centers in San Salvador, El Salvador, and Recife, Brazil. Median age at diagnosis was 4.9 years; 283 children had leukemia and 160 had solid tumors. Z-scores were calculated for weight for age (WAZ), height for age (HAZ), and weight for height (WHZ) at diagnosis. Z scores <-2 indicated malnutrition. Patients were also stratified by low-risk disease (solid tumors: stage I, stage II, or localized; acute lymphocytic leukemia: white blood cell count <25,000/μL, no central nervous system involvement, no mediastinal mass and age >1 and <10 yrs) and high-risk disease (all other patients, including those with acute or chronic myelocytic leukemia).
Results: Z-scores indicated malnutrition in 23.5% (WAZ), 22.8% (HAZ), and 15.7% (WHZ) of patients. Z-score was not significantly related to overall survival rates, to survival rates analyzed by type of malignancy or risk status, or to survival rates at the end of the first month of treatment.
Conclusions: We found no relationship between nutritional status and survival in these patients. This implies that future protocols for use in developing countries can be designed to provide optimal treatment intensity despite the high incidence of malnutrition.
Journal of Pediatric Hematology/Oncology 10/2000; 22(6):502-505. · 1.16 Impact Factor
