title: The magnitude and predictors of abandonment of therapy in paediatric acute leukaemia in middle-income countries: a systematic review and meta-analysis.
abstract: BACKGROUND
  Abandonment of therapy is a significant cause of paediatric cancer treatment failure in low- to middle-income countries (LMIC), but its impact has been underestimated. We performed a meta-analysis to determine the magnitude of abandonment in paediatric leukaemia in LMIC and sought to identify patient-, centre- and country-specific predictors of abandonment.
  
  
  METHODS
  We searched seven databases to identify paediatric oncology cohorts followed up from diagnosis and treated in LMIC. All languages were included. Two reviewers independently selected articles and extracted data. Authors were contacted for additional information. Subgroup analyses were planned a priori.
  
  
  RESULTS
  Of 22,384 publications, 318 in eight languages met criteria for full text review. 157 studies met analysis inclusion criteria. Abandonment rates (ARs), obtained for 83 of the 157 studies (52.9%), ranged from 0% to 74.5%. ARs were frequently unreported and available only directly from authors. Forty studies (10,494 children in 20 countries) were quantitatively analysed. ARs for acute lymphoblastic laeukemia in lower-middle-income countries (lower-MICs) were higher than in upper-middle-income countries (29%, 95% confidence interval (CI) 23-36% versus 2%, 95% CI 1-3%; p<0.0001) but were heterogeneous (I(2)=98%; p<0.0001). This heterogeneity was not explained by centre-specific (free versus paid treatment) or country-specific (government health expenditure, per-capital income) subgroups.
  
  
  CONCLUSIONS
  In LMICs, ARs are highest in lower-MICs. However, their broad range suggests that low ARs are possible in resource-constrained settings. Analysis of outliers may suggest interventions for use at other centres. Methodologically appropriate reporting of ARs should be adopted. Future research should evaluate interventions targeting abandonment.
authors.affiliation: Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Canada. Electronic address: sumit.gupta@sickkids.ca.
authors.forename: Sumit
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Stacy
authors.initials: S
authors.lastname: Yeh
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Martiniuk
authors.affiliation: International Outreach Program and Department of Oncology, St. Jude Children's Research Hospital, Memphis, USA.
authors.forename: Catherine G
authors.initials: CG
authors.lastname: Lam
authors.affiliation: Curtin-Monash Accident Research Center, Curtin University, Perth, Australia.
authors.forename: Heui-Yang
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Buddhist Tzu Chi General Hospital, Taipei Branch, Xindian, New Taipei, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Ingram School of Nursing, McGill University, Montreal, Canada.
authors.forename: Argerie
authors.initials: A
authors.lastname: Tsimicalis
authors.affiliation: Pediatric Oncology, Alder Hey Children's Hospital, Liverpool, UK.
authors.forename: Ramandeep S
authors.initials: RS
authors.lastname: Arora
authors.affiliation: International Outreach Program and Department of Oncology, St. Jude Children's Research Hospital, Memphis, USA.
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
mesh_terms: D000208:Acute Disease; D003906:Developing Countries; D005260:Female; D006801:Humans; D007938:Leukemia / Q000191:economics / Q000628:therapy*; D008297:Male; D016312:Treatment Refusal