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.

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.

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.

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.

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.

Political priority and pathways to scale-up of childhood cancer care in five nations.

BACKGROUND: Despite increasing global attention to non-communicable diseases (NCDs) and their incorporation into universal health coverage (UHC), the factors that determine whether and how NCDs are prioritized in national health agendas and integrated into health systems remain poorly understood. Childhood cancer is a leading non-communicable cause of death in children aged 0-14 years worldwide. We investigated the political, social, and economic factors that influence health system priority-setting on childhood cancer care in a range of low- and middle-income countries (LMIC). METHODS AND FINDINGS: Based on in-depth qualitative case studies, we analyzed the determinants of priority-setting for childhood cancer care in El Salvador, Guatemala, Ghana, India, and the Philippines using a conceptual framework that considers four principal influences on political prioritization: political contexts, actor power, ideas, and issue characteristics. Data for the analysis derived from in-depth interviews (n = 68) with key informants involved in or impacted by childhood cancer policies and programs in participating countries, supplemented by published academic literature and available policy documents. Political priority for childhood cancer varies widely across the countries studied and is most influenced by political context and actor power dynamics. Ghana has placed relatively little national priority on childhood cancer, largely due to competing priorities and a lack of cohesion among stakeholders. In both El Salvador and Guatemala, actor power has played a central role in generating national priority for childhood cancer, where well-organized and -resourced civil society organizations have disrupted legacies of fragmented governance and financing to create priority for childhood cancer care. In India, the role of a uniquely empowered private actor was instrumental in creating political priority and establishing sustained channels of financing for childhood cancer care. In the Philippines, the childhood cancer community has capitalized on a window of opportunity to expand access and reduce disparities in childhood cancer care through the political prioritization of UHC and NCDs in current health system reforms. CONCLUSIONS: The importance of key health system actors in determining the relative political priority for childhood cancer in the countries studied points to actor power as a critical enabler of prioritization in other LMIC. Responsiveness to political contexts-in particular, rhetorical and policy priority placed on NCDs and UHC-will be crucial to efforts to place childhood cancer firmly on national health agendas. National governments must be convinced of the potential for foundational health system strengthening through attention to childhood cancer care, and the presence and capability of networked actors primed to amplify public sector investments and catalyze change on the ground.

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.

Establishing Cancer Treatment Programs in Resource-Limited Settings: Lessons Learned From Guatemala, Rwanda, and Vietnam.

Purpose The global burden of cancer is slated to reach 21.4 million new cases in 2030 alone, and the majority of those cases occur in under-resourced settings. Formidable changes to health care delivery systems must occur to meet this demand. Although significant policy advances have been made and documented at the international level, less is known about the efforts to create national systems to combat cancer in such settings. Methods With case reports and data from authors who are clinicians and policymakers in three financially constrained countries in different regions of the world-Guatemala, Rwanda, and Vietnam, we examined cancer care programs to identify principles that lead to robust care delivery platforms as well as challenges faced in each setting. Results The findings demonstrate that successful programs derive from equitably constructed and durable interventions focused on advancement of local clinical capacity and the prioritization of geographic and financial accessibility. In addition, a committed local response to the increasing cancer burden facilitates engagement of partners who become vital catalysts for launching treatment cascades. Also, clinical education in each setting was buttressed by international expertise, which aided both professional development and retention of staff. Conclusion All three countries demonstrate that excellent cancer care can and should be provided to all, including those who are impoverished or marginalized, without acceptance of a double standard. In this article, we call on governments and program leaders to report on successes and challenges in their own settings to allow for informed progression toward the 2025 global policy goals.

Traditional and Complementary Medicine in Pediatric Oncology and Low-Middle Income Countries: Recommendations from the International Society of Pediatric Oncology (SIOP), T&CM Collaborative.

Significant strides have been made in the treatment of childhood cancer. Improvements in survival have led to increased attention toward supportive care indications; including the use of traditional and complementary medicine (T&CM). The use of T&CM among children and adolescents with cancer is well documented in both high-income countries (HICs) and low-middle income countries (LMICs). A higher incidence of the use of T&CM has been reported among children undergoing treatment in LMICs, which has elevated concerns related to drug interactions, adherence to therapy, and treatment-related toxicities. These observations have underscored the need for effective models of integrative care that are culturally sensitive yet sustainable in an LMIC setting. We present considerations inclusive of the clinical care, educational opportunities, governmental policy, and research priorities necessary for the development of models of integrative care for pediatric cancer units in an LMIC setting.

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.

Global Pediatric Oncology: Lessons From Partnerships Between High-Income Countries and Low- to Mid-Income Countries.

Partnerships between medical institutions in high-income countries (HICs) and low- to mid-income countries (LMICs) have succeeded in initiating and expanding pediatric cancer control efforts. The long-term goal is consistently a sustainable national pediatric cancer program. Here, we review the elements required for successful implementation, development, and long-term sustainability of pediatric cancer programs in LMICs that first arise as partnerships with institutions in HICs. Although plans must be adapted to each country's resources, certain components are unfailingly necessary. First, an essential step is provision of treatment regardless of ability to pay. Second, financial support for program development and long-term sustainability must be sought from sources both international and local, public and private. A local leader, typically a well-trained pediatric oncologist who devotes full-time effort to the project, should direct medical care and collaborate with hospital, governmental, and community leadership and international agencies. Third, nurses must be trained in pediatric cancer care and allowed to practice this specialty full-time. It is also essential to develop a grassroots organization, such as a foundation, dedicated solely to pediatric oncology. Its members must be trained and educated to provide pediatric cancer advocacy, fundraising, and (in concert with government) program sustainability. Finally, a project mentor in the HIC is crucial and should explore the possibility of collaborative research in the LMIC, which may offer significant opportunities. Relationships between the partnership's leaders and influential individuals in the community, hospital, grassroots foundation, and government will lay the foundation for productive collaboration and a sustainable pediatric oncology program.

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.

Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge.

Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported.

Supportive medical care for children with acute lymphoblastic leukemia in low- and middle-income countries.

In the last two decades, remarkable progress in the treatment of children with acute lymphoblastic leukemia has been achieved in many low- and middle-income countries (LMIC), but survival rates remain significantly lower than those in high-income countries. Inadequate supportive care and consequent excess mortality from toxicity are important causes of treatment failure for children with acute lymphoblastic leukemia in LMIC. This article summarizes practical supportive care recommendations for healthcare providers practicing in LMIC, starting with core approaches in oncology nursing care, management of tumor lysis syndrome and mediastinal masses, nutritional support, use of blood products for anemia and thrombocytopenia, and palliative care. Prevention and treatment of infectious diseases are described in a parallel paper.

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.

Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.

Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene.