title: Evaluation of minimal residual disease in high risk childhood acute lymphoblastic leukemia using an immunological approach during complete remission. AIEOP Cooperative Group for Immunology of Acute Leukemias.
abstract: BACKGROUND
  Sensitive methods for detecting residual disease may complement conventional morphology while monitoring the response to treatment in leukemia patients.
  
  
  METHODS
  We studied minimal residual disease (MRD) by selecting via a colony assay a peripheral blood (PB) cell population enriched in putative malignant cells and detecting occult leukemic cells by double immunologic analysis performed on colonyforming cells (CFC). Using this combined technique we assayed the PB of high risk children with acute lymphoblastic leukemia (ALL) in order to demonstrate possible differences in "the residual tumor cell burden" among leukemia patients and to correlate these with a 3-year clinical follow-up.
  
  
  RESULTS
  In all 22 patients positive results were obtained for up to 18 months following induction chemotherapy at times of apparent hematologic remission. Common ALL (cALL) patients exhibited a mean of 9.6% cAlla+ cells (range: 2% to 30%), whereas cALL antigen (cALLA) and cALLA/Tdt or CD1a/Tdt combination were never found in the colonies derived from healthy individuals. Six out of 22 cALL patients expressed a mean of 16.5% cALLA+/Tdt+ CFC (range: 2% to 35%). Five T-ALL children presented a mean of 24% CD1a/Tdt+ cells (range: 8% to 44%). Extensive follow-up indicates a correlation between the percentage of CFC Tdt+/lymphoid marker+ cells (more than 10%) and subsequent clinical relapse. In one patient relapse occurred after 16 months with a dramatic increase in the number of leukemic cells. In contrast, the decline in malignant cells, observed in two cases, predicted a favourable course. Five patients tested before autologous bone marrow transplantation (ABMT) presented high number of positive cells and relapsed at various times.
  
  
  CONCLUSIONS
  We conclude that this approach to the study of MRD could be valuable in monitoring the efficacy of chemotherapy, as well in evaluating the quality of purged marrow.
authors.affiliation: Istituto Clinica Pediatrica, Università di Pisa.
authors.forename: R
authors.initials: R
authors.lastname: Consolini
authors.forename: F
authors.initials: F
authors.lastname: Scamardella
authors.forename: A
authors.initials: A
authors.lastname: Legitimo
authors.forename: C
authors.initials: C
authors.lastname: Putti
authors.forename: D
authors.initials: D
authors.lastname: Granchi
authors.forename: P
authors.initials: P
authors.lastname: Paolucci
authors.forename: A
authors.initials: A
authors.lastname: Lippi
authors.forename: C
authors.initials: C
authors.lastname: Guazzelli
authors.forename: A
authors.initials: A
authors.lastname: Acquaviva
authors.forename: C
authors.initials: C
authors.lastname: Rosanda
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D012074:Remission Induction; D012307:Risk Factors