Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in pediatric t(8;21)-AML: Results from an international retrospective study by the International Berlin-Frankfurt-Münster Study Group

Kim Klein, Gertjan Kaspers, Christine J. Harrison, H. Berna Beverloo, Ardine Reedijk, Mathilda Bongers, Jacqueline Cloos, Andrea Pession, Dirk Reinhardt, Martin Zimmerman, Ursula Creutzig, Michael Dworzak, Todd Alonzo, Donna Johnston, Betsy Hirsch, Michal Zapotocky, Barbara De Moerloose, Alcira Fynn, Vincent Lee, Takashi TagaAkio Tawa, Anne Auvrignon, Bernward Zeller, Erik Forestier, Carmen Salgado, Walentyna Balwierz, Alexander Popa, Jeffrey Rubnitz, Susana Raimondi, Brenda Gibson

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Purpose: This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML). Patients and Methods: Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival. Results: Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m2 and etoposide doses greater than 500 mg/m2 in the first induction course and high-dose cytarabine 3 g/m2 during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m2 and etoposide greater than 1,500 mg/m2 were associated with lower CIR rates and better probability of event-free survival. Conclusion: Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide.

Original languageEnglish (US)
Pages (from-to)4247-4258
Number of pages12
JournalJournal of Clinical Oncology
Volume33
Issue number36
DOIs
StatePublished - Dec 20 2015

Bibliographical note

Funding Information:
We thank all participants of the various study groups for providing data.We thank Professor Adalet Meral Günes for providing the Turkish data, Marta Fiocco for additional statistical advice, and Vani Shanker from the Department of Scientific Editing at St Jude Children’s Research Hospital for revision of the manuscript. We thank the Swedish Childhood Cancer Foundation for supporting the Nordic Society of Paediatric Haematology and Oncology study group and the European Organisation for Research and Treatment of Cancer (EORTC) for permission to use the data from EORTC study 58921 for this research.

Fingerprint Dive into the research topics of 'Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in pediatric t(8;21)-AML: Results from an international retrospective study by the International Berlin-Frankfurt-Münster Study Group'. Together they form a unique fingerprint.

Cite this