title: Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with Down syndrome.
abstract: BACKGROUND
  Acute lymphoblastic leukemia (ALL) in children with Down syndrome (DS) presents with an increased incidence, higher frequency of adverse effects and inferior probability of survival. Attempts at improving outcomes face the dilemma posed by the need to avoid excessive toxicity while maintaining the efficacy of treatment. Dose reductions and avoidance of infusions of intermediate and high-dose methotrexate are common in this group.
  
  
  METHODS
  In a matched pair analysis we compared adverse effects and survival after ALL chemotherapy using intermediate and high doses of methotrexate in children with and without Down syndrome.
  
  
  RESULTS
  Following intermediate and high doses of methotrexate to treat primary ALL, children with DS did not require opiate analgesia and parenteral nutrition for severe mucositis more often than children without DS. Children with DS spent more days in hospital and missed more doses of maintenance chemotherapy. Chemotherapy dose reductions were common and in this study had no detectable adverse impact. Event-free and overall survival (OS) of children with ALL was lower in the DS than the non-Down syndrome (NDS) control group. The difference, however, was no longer significant during the recent treatment era.
  
  
  CONCLUSIONS
  The feasibility of all treatment elements that are efficacious in pediatric ALL needs to be carefully considered in children with DS. In addition to survival data, the prospective collection of data on both adverse events and treatment modifications is essential to strike a balance between the avoidance of adverse effects and the need for intensive therapy that will safely improve ALL outcomes in this group.
authors.affiliation: Division of Hematology/Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Niketa
authors.initials: N
authors.lastname: Shah
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Ahmari
authors.forename: Arwa
authors.initials: A
authors.lastname: Al-Yamani
authors.forename: Lee
authors.initials: L
authors.lastname: Dupuis
authors.forename: Derek
authors.initials: D
authors.lastname: Stephens
authors.forename: Johann
authors.initials: J
authors.lastname: Hitzler
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004314:Down Syndrome / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D016555:Matched-Pair Analysis; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D008727:Methotrexate