Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Munster (ALL-BFM) trials.
OBJECTIVE
We aimed to identify relapse predictors in children with a B-cell precursor acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21), a novel genetic entity associated with poor outcome.


METHODS
We screened 1,625 patients who were enrolled onto the Austrian and German ALL-Berlin-Frankfurt-Münster (ALL-BFM) trials 86, 90, 95, and 2000 with ETV6/RUNX1-specific fluorescent in situ hybridization probes, and we identified 29 patient cases (2%) who had an iAMP21. Minimal residual disease (MRD) was quantified with clone-specific immunoglobulin and T-cell receptor gene rearrangements.


RESULTS
Twenty-five patients were good responders to prednisone, and all achieved remission after induction therapy. Eleven patients experienced relapse, which included eight who experienced relapse after cessation of front-line therapy. Six-year event-free and overall survival rates were 37% +/- 14% and 66% +/- 11%, respectively. Results of MRD analysis were available in 24 (83%) of 29 patients: nine (37.5%) belonged to the low-risk, 14 (58.5%) to the intermediate-risk, and one (4%) to the high-risk group. MRD results were available in 8 of 11 patients who experienced a relapse. Seven occurred among the 14 intermediate-risk patients, and one occurred in the high-risk patient.


CONCLUSIONS
The overall and early relapse rates in the BFM study were lower than that in a previous United Kingdom Medical Research Council/Childhood Leukemia Working Party study (38% v 61% and 27% v 47%, respectively), which might result from more intensive induction and early reintensification therapy in the ALL-BFM protocols. MRD values were the only reliable parameter to discriminate between a low and high risk of relapse (P = .02).
Attarbaschi
Andishe
A
Department of Pediatric Hematology and Oncology, St Anna Children's Hospital, Vienna, Austria.
Mann
Georg
G
Panzer-Grümayer
Renate
R
Röttgers
Silja
S
Steiner
Manuel
M
König
Margit
M
Csinady
Eva
E
Dworzak
Michael N
MN
Seidel
Markus
M
Janousek
Dasa
D
Möricke
Anja
A
Reichelt
Carsten
C
Harbott
Jochen
J
Schrappe
Martin
M
Gadner
Helmut
H
Haas
Oskar A
OA
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome