title: Very early/early relapses of acute lymphoblastic leukemia show unexpected changes of clonal markers and high heterogeneity in response to initial and relapse treatment.
abstract: Minimal residual disease (MRD) quantified after induction treatment of childhood acute lymphoblastic leukemia (ALL) predicts risk of relapse. It has been assumed that early relapses derive from a residual population of leukemic cells, which is still present after induction and that relapsed disease will consequently be more resistant to treatment. To test these hypotheses, we performed a prospective study on patients treated according to the frontline-trial ALL-BFM 2000, which used MRD response for risk-group stratification. Patients (n=45) showed a median time to relapse of 1.5 years. In 89% of patients at least one T-cell-receptor/immunoglobulin gene rearrangement chosen for initial MRD quantification remained stable; however, at least one of the preferred markers for MRD stratification at relapse was different to diagnosis in 50% of patients. A similar proportion of very early, early and late relapses appeared to gain a marker at relapse although backtracking-analysis revealed that in 77% of cases, the gained markers were present as small sub-clones at initial diagnosis. Comparing initial and relapse MRD response to induction, 38% of patients showed a similar, 38% a better and 25% a poorer response after relapse. These data demonstrate an unexpectedly high clonal heterogeneity among very early/early relapses and challenge some current assumptions about relapsed ALL.
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany. cornelia.eckert@charite.de
authors.forename: C
authors.initials: C
authors.lastname: Eckert
authors.forename: T
authors.initials: T
authors.lastname: Flohr
authors.forename: R
authors.initials: R
authors.lastname: Koehler
authors.forename: N
authors.initials: N
authors.lastname: Hagedorn
authors.forename: A
authors.initials: A
authors.lastname: Moericke
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.forename: R
authors.initials: R
authors.lastname: Kirschner-Schwabe
authors.forename: G
authors.initials: G
authors.lastname: Cario
authors.forename: Av
authors.initials: A
authors.lastname: Stackelberg
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: A
authors.initials: A
authors.lastname: Schrauder
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012008:Recurrence
chemical_list: D011948:Receptors, Antigen, T-Cell