title: [Minimal residual disease in acute lymphoblastic leukemia: a new concept of complete remission].
abstract: BACKGROUND
  Early response to induction treatment is one of the most important prognostic factors in children with acute lymphoblastic leukemia (ALL). Cytological remission is currently achieved in 95-98 % of these patients, although a significant proportion will later relapse. More sensitive techniques are required to measure residual leukemia and establish a new definition of complete remission.
  
  
  OBJECTIVE
  To identify minimal residual disease (MRD) by immunological techniques and define its prognostic impact in children with ALL.
  
  
  METHODS
  MRD was studied by flow cytometry in 53 children diagnosed in our department between June 1999 and April 2003 and treated using the Pethema protocols. All the children achieved complete cytological remission (< 5 %) with the induction treatment and had at least one useful phenotype for follow-up: 11 % were T phenotype, one was biphenotypic and the remainder were B cell leukemias. Bone marrow samples were analyzed post-induction, post-consolidation, after 6 and 11 months of maintenance treatment, at the end of treatment, and 3 months later. The positivity threshold was set at 0.01 % and the sensitivity of the technique was 1 x 10(-4)-1 x 10(-5).
  
  
  RESULTS
  A total of 199 samples were analyzed. Thirty-seven percent of the post-induction and 20 % of the post-consolidation samples analyzed were MRD-positive. Elimination was slower in patients with a T phenotype and in high-risk patients according to the traditional classification. After a median follow-up of 26 months, event free survival (EFS) in the group as a whole was 92 %. The EFS rate in the patients who were MRD-positive post-induction was 79 %. None of the patients who were MRD-negative post-induction has developed recurrence.
  
  
  CONCLUSIONS
  Study of MRD is essential and should be included in all current treatment protocols for children with ALL. Its usefulness derives from the prognostic impact of the response to induction treatment. Continued sequential monitoring may predict recurrence before the onset of clinical or hematologic manifestations.
authors.affiliation: Servicio de Oncohematología Infantil, Hospital Universitario Materno-Infantil Vall d'Hebron, Barcelona, España. pbastida@vhebron.net
authors.forename: P
authors.initials: P
authors.lastname: Bastida Vilá
authors.forename: C
authors.initials: C
authors.lastname: Palacio García
authors.forename: M
authors.initials: M
authors.lastname: Solsona Riera
authors.forename: J J
authors.initials: JJ
authors.lastname: Ortega Aramburu
authors.forename: J
authors.initials: J
authors.lastname: Sánchez de Toledo Codina
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000453:epidemiology*; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology*; D012074:Remission Induction