Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98.
OBJECTIVE
Because cytogenetic data are essential for risk stratification of childhood acute myeloid leukemia (AML), the impact of chromosomal aberrations is crucial.


METHODS
Data of a large group of patients younger than 18 years treated according to study AML-Berlin-Frankfurt-Münster (BFM) 98 (n = 454), including their cytogenetics, were analyzed.


RESULTS
The favorable outcome in the subgroups of patients with t(8;21), inv(16), and t(15;17), with an overall survival of 91% (SE, 4%), 92% (SE, 6%), and 87% (SE, 5%), respectively, was confirmed. Within this group, the 5-year probability of event-free survival (pEFS) of all 17 children with t(8;21) and additional aberrations apart from del(9q) or -X/-Y was 100%. As expected, the cytogenetic finding of a complex karyotype (n = 35; pEFS, 33%; SE, 8%) or a monosomy 7 (n = 12; pEFS, 17%; SE, 11%) was associated with a poor outcome. Compared with remaining patients with cytogenetic data (pEFS, 48%; SE, 2%), prognosis in patients with an MLL rearrangement (n = 91) was inferior (pEFS, 34%; SE, 5%; P = .0005). Particularly, children with t(9;11) and additional aberrations (n = 13; pEFS, 31%; SE, 14%) and MLL rearrangements other than t(9;11) and t(11;19) (n = 41; pEFS, 24%; SE, 7%) had an unfavorable outcome. Nine patients with aberrations in 12p showed an adverse prognosis (pEFS, 11%; SE, 10%). The outcome of patients with aberrations of chromosome 5 (n = 13) was better than expected (pEFS, 50%; SE, 13%).


CONCLUSIONS
Because the prognostic value of rare recurrent chromosomal aberrations still has to be elucidated, these data will contribute to future risk stratification for the treatment of pediatric AML.
von Neuhoff
Christine
C
Pediatric Hematology and Oncology, Medical School Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany. neuhoff.christine.von@mh-hannover.de
Reinhardt
Dirk
D
Sander
Annette
A
Zimmermann
Martin
M
Bradtke
Jutta
J
Betts
David R
DR
Zemanova
Zuzana
Z
Stary
Jan
J
Bourquin
Jean-Pierre
JP
Haas
Oskar A
OA
Dworzak
Michael N
MN
Creutzig
Ursula
U
D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D003561:Cytarabine / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D008297:Male; D011336:Probability; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D015255:Idarubicin