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J Clin Oncol. 2015 Dec 20;33(36):4247-58. doi: 10.1200/JCO.2015.61.1947. Epub 2015 Nov 16.

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.

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1
Kim Klein, Gertjan Kaspers, Jacqueline Cloos, and Mathilda Bongers, Vrije Universiteit University Medical Center Amsterdam; Gertjan Kaspers and Ardine Reedijk, Dutch Childhood Oncology Group, The Hague; H. Berna Beverloo, Erasmus Medical Center, Rotterdam, the Netherlands; Christine J. Harrison, Newcastle University, Newcastle upon Tyne; Brenda Gibson, Royal Hospital for Sick Children, Glasgow, United Kingdom; Andrea Pession, Italian Association of Pediatric Hematology Oncology, Bologna, Italy; Dirk Reinhardt, Berlin-Frankfurt-Münster (BFM) -Germany, Essen; Martin Zimmerman and Ursula Creutzig, BFM-Germany, Hannover, Germany; Michael Dworzak, BFM-Austria, Vienna, Austria; Todd Alonzo, Donna Johnston, and Betsy Hirsch, Children's Oncology Group (COG) including Children's Cancer Group and Pediatric Oncology Group, Philadelphia (COG chair's office), PA; Michal Zapotocky, Czech Paediatric Hematology Working Group, Prague, Czech Republic; Barbara De Moerloose, European Organisation for Research and Treatment of Cancer-Children's Leukemia Group, Brussels, Belgium; Alcira Flynn, Grupo Argentino de Tratamiento de la Leucemia Aguda, Buenos Aires, Argentina; Vincent Lee, Hong Kong Paediatric Haematology and Oncology Study Group, Hong Kong, Special Administrative Region, People's Republic of China; Takashi Taga, Japanese Pediatric Leukemia/Lymphoma Study Group, Otsu; Akio Tawa, Japanese Pediatric Leukemia/Lymphoma Study Group, Osaka, Japan; Anne Auvrignon, French Leucémie Aiguë Myéloblastique Enfant Cooperative Group, Paris, France; Bernward Zeller, Nordic Society of Paediatric Haematology and Oncology, Oslo, Norway; Erik Forestier, Nordic Society of Paediatric Haematology and Oncology, Umeå, Sweden; Carmen Salgado, The National Program for Antineoplastic Drugs for Children, Santiago, Chile; Walentyna Balwierz, Polish Pediatric Leukemia Lymphoma Study Group, Krakow, Poland; Alexander Popa, Russian Acute Myeloid Leukemia Study Group, Moscow, Russia; and Jeffrey Rubnitz and

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/m(2) and etoposide doses greater than 500 mg/m(2) in the first induction course and high-dose cytarabine 3 g/m(2) during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m(2) and etoposide greater than 1,500 mg/m(2) 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.

PMID:
26573082
PMCID:
PMC5321085
DOI:
10.1200/JCO.2015.61.1947
[Indexed for MEDLINE]
Free PMC Article

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