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.

Abstract

PURPOSE:

Because cytogenetic data are essential for risk stratification of childhood acute myeloid leukemia (AML), the impact of chromosomal aberrations is crucial.

PATIENTS AND 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%).

CONCLUSION:

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.

• Authors: Christine von Neuhoff, Dirk Reinhardt, Annette Sander, Martin Zimmermann, Jutta Bradtke, David R Betts, Zuzana Zemanova, Jan Stary, Jean-Pierre Bourquin, Oskar A Haas, Michael N Dworzak, Ursula Creutzig
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 16 Pg. 2682-9 (Jun 01 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20439630 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cytarabine
• Etoposide
• Idarubicin

Topics

• Adolescent
• Age Factors
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Child
• Child, Preschool
• Chromosome Aberrations
• Chromosomes, Human, Pair 21
• Chromosomes, Human, Pair 8
• Combined Modality Therapy
• Confidence Intervals
• Cytarabine (administration & dosage)
• Cytogenetic Analysis
• Disease-Free Survival
• Etoposide (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Idarubicin (administration & dosage)
• In Situ Hybridization, Fluorescence
• Leukemia, Myeloid, Acute (diagnosis, genetics, mortality, therapy)
• Male
• Probability
• Proportional Hazards Models
• Radiotherapy, Adjuvant
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Assessment
• Severity of Illness Index
• Statistics, Nonparametric
• Stem Cell Transplantation
• Survival Analysis
• Transplantation, Homologous
• Treatment Outcome