title: Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome.
abstract: The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day 15 (D15) and day 29 (D29) after the start of induction therapy (r(s) = 0.70, P <.0001). The 15 patients with T-cell disease had higher D29 MRD than those with B-lineage ALL (P =.01). Age was positively related to D29 MRD (r(s) = 0.32, P =.001). The 16 patients who had a relapse had higher D15 and D29 MRD levels than the patients who stayed in remission (median levels D15, 1% versus 0.1%, P =.03; D29, 0.4% versus 0.01%, P =.0001). No patients with a MRD level less than 0.01% on D29 have so far had a relapse, whereas the 7-year probability of event-free survival for patients with higher MRD levels was 0.52 (P =.0007). The group of patients with a D29 MRD less than 0.01% included patients with T-cell disease, white blood cell count more than 50 x 10(9)/L at diagnosis, or age 10 years or older, and could not be identified by up-front criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD (P =.004) and age (P =.009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a very low risk of relapse. Further trials are needed to reveal whether such patients with D29 MRD less than 0.01% can be cured with less intensive chemotherapy, which would reduce the risk of serious late effects as well as the costs of therapy.
authors.affiliation: Department of Clinical Immunology and Department of Pediatrics, National University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nyvold
authors.forename: Hans O
authors.initials: HO
authors.lastname: Madsen
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: Jeanette
authors.initials: J
authors.lastname: Seyfarth
authors.forename: Arne
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.forename: Finn
authors.initials: F
authors.lastname: Wesenberg
authors.forename: Olafur G
authors.initials: OG
authors.lastname: Jonsson
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007223:Infant; D008297:Male; D008954:Models, Biological; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007143:Immunoglobulin Heavy Chains; D011948:Receptors, Antigen, T-Cell