TY - JOUR
T1 - Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in pediatric t(8;21)-AML
T2 - Results from an international retrospective study by the International Berlin-Frankfurt-Münster Study Group
AU - Klein, Kim
AU - Kaspers, Gertjan
AU - Harrison, Christine J.
AU - Berna Beverloo, H.
AU - Reedijk, Ardine
AU - Bongers, Mathilda
AU - Cloos, Jacqueline
AU - Pession, Andrea
AU - Reinhardt, Dirk
AU - Zimmerman, Martin
AU - Creutzig, Ursula
AU - Dworzak, Michael
AU - Alonzo, Todd
AU - Johnston, Donna
AU - Hirsch, Betsy
AU - Zapotocky, Michal
AU - De Moerloose, Barbara
AU - Fynn, Alcira
AU - Lee, Vincent
AU - Taga, Takashi
AU - Tawa, Akio
AU - Auvrignon, Anne
AU - Zeller, Bernward
AU - Forestier, Erik
AU - Salgado, Carmen
AU - Balwierz, Walentyna
AU - Popa, Alexander
AU - Rubnitz, Jeffrey
AU - Raimondi, Susana
AU - Gibson, Brenda
N1 - 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.
Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/12/20
Y1 - 2015/12/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2015.61.1947
DO - 10.1200/JCO.2015.61.1947
M3 - Article
C2 - 26573082
AN - SCOPUS:84957575488
SN - 0732-183X
VL - 33
SP - 4247
EP - 4258
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -
