Rhabdomyosarcoma in low- and middle-income countries: A report from the Asociacion de Hemato-oncología Pediatrica de Centro América (AHOPCA).

This report describes the results of an observational study dedicated to rhabdomyosarcoma developed by the Asociación de Hemato-oncología Pediatrica de Centro América (AHOPCA) between 2001 and 2018. Overall, 337 previously untreated patients < 18 years old were included in the analysis; 58% had unresected disease, and 19% were metastatic at diagnosis. With a median follow-up of 6.6 years, five-year event-free and overall survival rates were 30% and 33%, respectively. Local progression/relapse was the main cause of treatment failure.

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

Nutritional status at diagnosis of cancer in children and adolescents in Guatemala and its relationship to socioeconomic disadvantage: A retrospective cohort study.

BACKGROUND: At least 80% of children with cancer live in low- and middle-income countries where the prevalence of malnutrition and socioeconomic disadvantage is high. We examined the relationship between nutritional status (NS), assessed by arm anthropometry, and socioeconomic status (SES) in children diagnosed with cancer at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala over a three-year period. METHOD: Patients aged 0 to 18 years of age diagnosed between January 2015 and December 2017 were included. NS was evaluated by mid-upper arm circumference, triceps skin fold thickness, and serum albumin level, and subjects were classified as adequately nourished, moderately depleted, and severely depleted nutritionally. SES was measured by a 15-item instrument developed at UNOP. RESULTS: Of 1365 patients diagnosed in the study period, 1060 (78%) fulfilled the eligibility criteria. Only 6% of patients were classified as medium to high, the remainder as medium-low to extremely low SES. Almost 47% were severely depleted at diagnosis, 19% moderately depleted, and 34% adequately nourished. SES was shown to be a determinant of NS; with progressively lower SES, the probability of a decline in NS increased by a factor of 1.04 points (P < 0.0001). Leukemia and lymphoma were also important predictors of nutritional depletion with odds ratios of 6.08 (95% CI, 1.74-28.28; P = 0.008) for leukemias and 4.83 (95% CI, 1.33-23.03; P = 0.03) for lymphomas. CONCLUSION: Both low SES and a diagnosis of leukemia or lymphoma are strong predictors of poor NS at diagnosis in children with cancer in Guatemala.

The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results.

BACKGROUND: The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato-oncology center in Guatemala. METHODS: Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin-Frankfurt-Münster (IC-BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy. RESULTS: From July 2007 to June 2014, 787 patients were treated, including 160 who had standard-risk ALL, 450 who had intermediate-risk ALL, and 177 who had high-risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5-year event-free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5-year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty-one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt-related transcription factor 1 (ETV6/RUNX1) fusion. CONCLUSIONS: A well organized center in a low-middle-income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436-448. © 2016 American Cancer Society.

Anaplastic Large Cell Lymphoma in Central America: A Report From the Central American Association of Pediatric Hematology Oncology (AHOPCA).

BACKGROUND: Although anaplastic large cell lymphoma (ALCL) is curable in high-income countries (HIC), data from low- and middle-income countries (LMIC) are lacking. We therefore conducted a retrospective study of the Central American Association of Pediatric Hematology Oncology (AHOPCA) experience in treating ALCL. PROCEDURE: We included all patients age <18 years newly diagnosed with ALCL treated between 2000 and 2013 in seven AHOPCA institutions. Retrospective data were extracted from the Pediatric Oncology Network Database. RESULTS: Thirty-one patients met inclusion criteria. Twenty-five (81%) had advanced disease (stages III and IV), six (19%) were treated on the APO (doxorubicin, prednisone, vincristine) regimen, 15 (49%) on multi-agent chemotherapy designed for T-cell lineage malignancies (GuatALCL protocol), and 10 (32%) on BFM-based treatment regimens. Five-year overall event-free survival and overall survival were, respectively, 67.1 ± 8.6% and 66.7 ± 8.7%. All 10 events occurred in patients treated on BFM-based treatment regimens or the GuatALCL protocol, none on APO treatment: two patients experienced relapse, six treatment related mortality (TRM), and two abandonment. CONCLUSIONS: Treatment of ALCL in countries with limited resources is feasible with similar outcomes as in HIC, though the causes of treatment failure differ. Less intensive regimens may be preferable in order to decrease TRM and improve outcomes. Prospective clinical trials determining the ideal treatment for LMIC children with ALCL are necessary.

Use of traditional and complementary/alternative medicine (TCAM) in children with cancer in Guatemala.

BACKGROUND: International surveys have demonstrated that use of traditional and complementary/alternative medicine (TCAM) is highly prevalent among children with cancer; however, little is known about its use among children with cancer in Latin America. As part of a regional initiative, we present the results of the first survey exploring use of TCAM among children with cancer residing in Latin America. PROCEDURE: A cross-sectional sample of 100 parents whose children received treatment in Guatemala City were interviewed from May 2008 to February 2010. Upon consent, an in-person interview was performed during a routine clinical visit. Information on the form, duration, cost, and satisfaction of TCAM was collected. Approval from the institutional review board was obtained. RESULTS: The median age of patients was 9.2 years with 63% undergoing treatment. Use of TCAM was reported by 90% of parents. Most often, more than one type of therapy was utilized. Most patients (67%) relied on TCAM for supportive care indications; however, a significant percentage (34%) used TCAM for curative purposes. The most commonly reported form was the use of oral supplements with the majority perceiving TCAM as effective for the intended purpose. CONCLUSIONS: Use of TCAM was highly prevalent among children with cancer residing in Guatemala. Most importantly, TCAM was used alongside conventional therapy for supportive care indications. These findings underscoring the need for open lines of communication between clinicians and families. Future research may consider exploring the role of TCAM within the scope of supportive care and its effect on existing supportive care interventions.

Outcome of children treated for relapsed acute myeloid leukemia in Central America.

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 × 10(9) /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.

Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America.

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 2013. © 2012 American Cancer Society.

Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala.

BACKGROUND: Most children with cancer live in developing countries where the prevalence of malnutrition may reach 50% and influence the course of the disease. This study examined the prevalence and severity of malnutrition at diagnosis, as well as after 3 and 6 months of chemotherapy, in children with acute lymphoblastic leukemia (ALL) in Guatemala. METHODS: Triceps skin fold thickness (TSFT) and mid upper arm circumference (MUAC) provided measures of nutritional status (NS) in three categories: adequately nourished (A): TSFT and MUAC > 10th percentile; severely depleted (SD): TSFT or MUAC < 5th percentile; and moderately depleted (MD): all the remaining patients. RESULTS: Of 331 new patients, 241 had NS assessed at diagnosis. A = 113 (46.9%); MD = 28 (11.6%); SD = 100 (41.5%). At 3 months A = 106 (52.2%); MD = 25 (12.3%); SD = 72 (35.5%). At 6 months A = 146 (76.0%); MD = 12 (6.3%); SD = 34 (17.7%). In multivariate analysis, SD children at 6 months of treatment had a hazard of death that was 2.4-fold the hazard of those A or MD (95% CI: 1.3-4.7) CONCLUSIONS: Malnutrition is prevalent in newly diagnosed children with ALL in Guatemala and severe nutritional depletion is apparently predictive of abandonment of therapy and relapse of disease, but if children survive and improve their NS in the first 6 months after diagnosis, their chances of survival may improve significantly to approximate those in children not presenting with nutritional depletion.

Use of Joint Commission International standards to evaluate and improve pediatric oncology nursing care in Guatemala.

BACKGROUND: Inadequate nursing care is a major impediment to development of effective programs for treatment of childhood cancer in low-income countries. When the International Outreach Program at St. Jude Children's Research Hospital established partner sites in low-income countries, few nurses had pediatric oncology skills or experience. A comprehensive nursing program was developed to promote the provision of quality nursing care, and in this manuscript we describe the program's impact on 20 selected Joint Commission International (JCI) quality standards at the National Pediatric Oncology Unit in Guatemala. We utilized JCI standards to focus the nursing evaluation and implementation of improvements. These standards were developed to assess public hospitals in low-income countries and are recognized as the gold standard of international quality evaluation. METHODS: We compared the number of JCI standards met before and after the nursing program was implemented using direct observation of nursing care; review of medical records, policies, procedures, and job descriptions; and interviews with staff. RESULTS: In 2006, only 1 of the 20 standards was met fully, 2 partially, and 17 not met. In 2009, 16 were met fully, 1 partially, and 3 not met. Several factors contributed to the improvement. The pre-program quality evaluation provided objective and credible findings and an organizational framework for implementing change. The medical, administrative, and nursing staff worked together to improve nursing standards. CONCLUSION: A systematic approach and involvement of all hospital disciplines led to significant improvement in nursing care that was reflected by fully meeting 16 of 20 standards.

POND4Kids: a global web-based database for pediatric hematology and oncology outcome evaluation and collaboration.

The Pediatric Oncology Network Database, (www.pond4kids.org, POND), is a secure, web-based, multilingual pediatric hematology/oncology database created for use in countries with limited resources to meet various clinical data management needs including cancer registration, delivery of protocol-based care, outcome evaluation, and assessment of psychosocial support programs. Established as a part of the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee, POND serves as a tool for oncology units to store patient data for easy retrieval and analysis and to achieve uniform data collection to facilitate meaningful comparison of information among centers. Launched in 2003, POND now has 233 sites registered with over 1,000 users in 66 countries. However, adoption and usage of POND varies widely among sites. This paper reviews some of the challenges to developing a global collaborative clinical platform based on the experiences of developing POND. The paper also presents a case study of POND use in Guatemala, where the Guatemalan National Oncology Unit (UNOP) has developed extensive internal and external global collaborations using POND.

Pediatric oncology research in low income countries: ethical concepts and challenges.

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.

A sustainable model for pediatric oncology nursing education in low-income countries.

Effectiveness of a nurse educator in the pediatric oncology unit in Guatemala was assessed by measuring completion of an education course, chemotherapy and central line competency, continuing education, and cost. All newly hired nurses completed the education course. Of the nurses employed, 86% participated in the chemotherapy course, and 93% achieved competency; 57% participated in the central line course, and 79% achieved competency. The nurses completed a mean of 26 hours continuing education yearly. The annual direct cost of the educator ($244/nurse) was markedly less than other models. This is an effective and sustainable means to educate nurses in low-income countries.

Impact of dry hydrogen peroxide on hospital-acquired infection at a pediatric oncology hospital.

BACKGROUND: This study aims to describe the effect of Dry Hydrogen Peroxide (DHP), as an adjunct to environmental cleaning and disinfection, on the incidence of hospital-acquired infections (HAIs) at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala City, Guatemala. METHODS: A retrospective study of all HAI data from the hospital's surveillance system, which follows Centers for Disease Control and Prevention (CDC) protocols, was conducted from January 2019 to November 2020. DHP was installed in all Pediatric Intensive Care Unit (PICU) rooms in January 2020, but nowhere else in the hospital, including the Intermediate Care Unit (IMCU). RESULTS: There were 189 HAI cases during the study period, with 173 occurring in either the PICU or IMCU. A statistically significant decrease in HAI incidence rates occurred in the PICU in 2020 compared to 2019 (P = .028), including Clostridiodes-associated gastroenteritis (P = .048). Logistic multivariate regression yielded a significant association between DHP exposure and reduced odds of developing an HAI during the study (OR = 0.3857, P = .029). CONCLUSION: The use of DHP as an adjunct technology for environmental cleaning and disinfection contributed to the reduction in HAIs in the PICU. Our study highlights the value of such an approach as an addition to manual cleaning to decrease the risk of infection from environmental contamination.

High morbidity and mortality associated with primary bloodstream infections among pediatric patients with cancer at a Guatemalan tertiary referral hospital.

Infectious complications remain major contributors to adverse outcomes in patients treated for non-communicable disease, particularly in resource limited settings. We performed a 5-year retrospective study of primary bloodstream infections at a dedicated pediatric oncology center in Guatemala. Two hundred and twelve episodes occurring in 194 unique patients qualified for inclusion. Patients required intensive care unit admission in 55% of episodes and death occurred in 24% of episodes. Despite subspecialty support in infectious diseases, poor outcomes, including prolonged hospitalization and mortality, were frequent. Our findings suggest that investments in laboratory and clinical data collection are critical to understanding the contributors to poor outcomes and therefore to improving the quality of bloodstream infection management in resource limited settings.

Treatment-related mortality in children with acute lymphoblastic leukemia in Central America.

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 × 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). 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.

POND4Kids: a web-based pediatric cancer database for hospital-based cancer registration and clinical collaboration.

The Pediatric Oncology Network Database, POND4Kids (www.pond4kids.org, POND), is an online, multilingual clinical database created for use by pediatric oncology units in countries with limited resources to meet various clinical data management needs including cancer registration, data collection and changes in treatment outcome. Established as a part of the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee, POND aims to provide oncology units a tool to store patient data for easy retrieval and analysis and to achieve uniform data collection to facilitate meaningful comparison of information among centers. Currently, POND is being used to store clinical data on thousands of patients and measure their treatment improvement over a period of time. In 2009 POND included more than 100 pediatric oncology units; each has its own virtual private area. A case study of the UNOP Guatemala Clinic's use of POND is presented. On-going challenges at partner sites include inconsistent data collection methods, missing records, training for data managers, and slow or unreliable internet connections.

Identifying and Prioritizing Family Education Needs at Pediatric Oncology Centers in Central America and Mexico.

METHODS: A qualitative study involving 72 in-person interviews and 4 focus groups was conducted using a semistructured interview guide. Key informants included family members, physicians, nurses, psychosocial providers, foundation leadership, volunteers, and communication professionals. The study sites included pediatric oncology centers in El Salvador, Guatemala, Mexico, and Panama. NVivo was used for thematic analysis. RESULTS: Across all sites, parents had common questions and educational needs. Questions from families focused on their child's likelihood of dying from cancer and feelings of guilt that were based on their perception that they caused the disease. The origin of cancer, nutrition, and psychosocial support were the most important educational themes. However, the prioritization of different educational themes varied on the basis of cultural or social influences unique to each site. Some of these differences included a need for education surrounding amputations, sibling support, and alternative or traditional healers. CONCLUSION: This study demonstrates that although many educational needs were consistent across hospitals, some of the educational priorities differed by site despite geographic proximity and shared language. Developing an educational program in resource-limited settings can be challenging, but it is an important contributor to improving childhood cancer outcomes that should be tailored to the specific needs of a site. This study can be used as a guide for other programs with limited resources wanting to develop relevant educational materials for families.