Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador
Introduction
In high-income countries (HICs), over 80% of children with acute lymphoblastic leukaemia (ALL) are cured.1, 2 Unfortunately, cure rates are inferior in low-income countries (LICs), where the majority of children with cancer reside.3 Various phenomena may account for this survival gap, including more treatment toxicity, higher rates of relapse and abandonment of therapy in LICs.
Improvement in survival in HICs has been dependent on the identification of clinical and biological predictors of outcome and the development of various risk stratification schemas.4 This in turn has allowed the tailoring of treatment intensity to disease aggressiveness, avoiding both over- and under-treatment of individual patients. The success of this approach has resulted in several traditional adverse prognostic factors losing their predictive power in the context of modern treatment.1, 2
Risk stratification systems developed in HICs may not, however, be appropriate for children with ALL in LICs. Several routine risk factors, such as cytogenetics and minimal residual disease, are not commonly available in low-income centres. In addition, differences in the underlying biology and the external circumstances are likely to require the adaptation of traditional risk strata. Socioeconomic and nutritional factors may also play important roles.
Finding accurate predictors of outcome is essential if LICs are to close the survival gap which currently exists in ALL. The appropriate balancing of treatment intensity to risk of relapse and treatment-related mortality (TRM) is of particular importance in LICs given the significant resource constraints and difficulties in supportive care.5 Despite this, few investigators have systematically examined the risk factors for survival in paediatric ALL in LICs. The primary objectives of this study were therefore to determine predictors of event-free survival (EFS) in children with ALL treated in El Salvador, an LIC. The secondary objectives were to describe overall survival (OS) and the relationship between EFS and OS in this population.
Section snippets
Data source
Data were obtained from two sources. The primary source of data was the Paediatric Oncology Networked Database (POND) (www.pond4kids.org). POND is an online database for paediatric cancer patient information designed to permit users at multiple locations to store and analyse data that include patient demographics, diagnoses, treatments and outcomes in a secure environment with stringent control of access and privacy.6 Although data collection is primarily to assist in patient outcome monitoring
Results
The study sample included 443 children with ALL treated according to the EGH II protocol. Two hundred and sixty (58.7%) were classified as standard risk while the remainder classified as high risk. Demographic characteristics of the patient population can be seen in Table 1.
The 5 year EFS was 56.3 ± 4.5% and 48.6 ± 5.5% for the standard- and high-risk cohorts, respectively. The 5 year OS was 77.7 ± 3.8% and 61.9 ± 5.8% for standard- and high-risk patients (Fig. 1). There were 82 events among
Discussion
This study found that among the children with ALL treated in El Salvador, the 5 year EFS was 56.3 ± 4.5% and 48.6 ± 5.5% for the standard- and high-risk patients, while the 5 year OS was 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among the standard-risk cohort, socioeconomic variables predicted EFS, while only disease-related variables did so in the high-risk children.
One striking finding is the wide and sustained gap between EFS and OS in both standard- and high-risk patients. In HICs, this difference
Sources of support
This work was supported in part by the Paediatric Oncology Group of Ontario, the American Lebanese Syrian Associated Charities and the Fundación Ayúdame a Vivir de El Salvador.
Conflict of interest statement
None declared.
Acknowledgements
L.S. is supported by the Canadian Childhood Clinician Scientist Training Program, a training program of the Canadian Institutes of Health Research. This work was supported in part by the Paediatric Oncology Group of Ontario, the American Lebanese Syrian Associated Charities and the Fundación Ayúdame a Vivir de El Salvador. Funding sources had no role in the writing of the manuscript or the decision to submit it for publication.
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Cited by (30)
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Childhood cancer mortality trends in Europe, 1990-2017, with focus on geographic differences
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2015, European Journal of Oncology NursingThe magnitude and predictors of abandonment of therapy in paediatric acute leukaemia in middle-income countries: A systematic review and meta-analysis
2013, European Journal of CancerCitation Excerpt :Nine studies defined abandonment, ranging from 4 to 12 weeks of missed therapy.17,19–26 Only two studies actively followed up cases of abandonment to minimise misclassification.21,22 For meta-analysis, all studies reporting ARs that included upfront refusal were assembled and narrowed to one study per institution, leaving 40 studies representing 10,494 children in 20 countries (Supplemental Table 2).
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2013, Journal of Cancer PolicyCitation Excerpt :However, as invaluable as these guideline and recommendations are, implementation has lagged, so there is limited documentation of successful models of resource-appropriate cancer care collaboration between high-income countries and low- and middle-income countries (HC–LMC collaborations) in the literature. The program descriptors and documentation of programmatic evolution in pediatric oncology, mainly from the Monzas International School of Pediatric Hematology/Oncology (MISPHO) and the St. Jude International Outreach Program, (IOP), form the bulk of the published literature [14–19]. More recently, descriptors of the process and implementation of creating a breast-specific cancer care delivery system have been published [20].
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Contributed equally to this manuscript.