title: A strategy to improve treatment-related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays.
abstract: BACKGROUND
  Treatment-related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.
  
  
  METHODS
  A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper-middle income country, and Dana-Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced-intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.
  
  
  RESULTS
  The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995-2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event-free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease-free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high-income countries.
  
  
  CONCLUSIONS
  Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL.
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Amaranto
authors: A
authors: Suarez
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Martha
authors: M
authors: Piña
authors: Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Diana X
authors: DX
authors: Nichols-Vinueza
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: John
authors: J
authors: Lopera
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Lyda
authors: L
authors: Rengifo
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Mauricio
authors: M
authors: Mesa
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Marcela
authors: M
authors: Cardenas
authors: Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Lisa
authors: L
authors: Morrissey
authors: Department of Surgery, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Galo
authors: G
authors: Veintemilla
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Martha
authors: M
authors: Vizcaino
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Ligia
authors: L
authors: Del Toro
authors: Department of Pediatrics, Instituto Nacional de Cancerologia, Bogota, Colombia.
authors: Victor
authors: V
authors: Vicuna
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Jorge
authors: J
authors: Fernandez
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Donna
authors: D
authors: Neuberg
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Kristen
authors: K
authors: Stevenson
authors: Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Alejandro
authors: A
authors: Gutierrez
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003906:Developing Countries; D018572:Disease-Free Survival; D005260:Female; D054625:Healthcare Disparities; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents
keywords: ALL; outcomes research; pediatric hematology/oncology