Clinical Impact of Additional Cytogenetic Aberrations, cKIT and RAS Mutations, and Treatment Elements in Pediatric t(8;21)- XXXX : Results From an International Retrospective Study by the International Berlin-Frankfurt-M  nster Study Group.

@entity1 @entity8253 @entity5948 @entity2879 @entity2592 @entity3052
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 @entity1 with @entity3052 ( @entity3052 ). @entity1 AND METHODS: Karyotypes of 916 pediatric @entity1 with t(8;21)- @entity3052 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 @entity8253 , @entity2592 , and @entity2879 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 @entity1 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. @entity1 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). @entity5948 doses greater than 150 mg/m(2) and @entity2879 doses greater than 500 mg/m(2) in the first induction course and high-dose @entity2592 3 g/m(2) during induction were associated with better outcomes on various end points. Cumulative doses of @entity2592 greater than 30 g/m(2) and @entity2879 greater than 1,500 mg/m(2) were associated with lower CIR rates and better probability of event-free survival. CONCLUSION: Pediatric @entity1 with t(8;21)- @entity3052 and additional del(9q) or additional +4 might not be considered at good risk. @entity1 with t(8;21)- @entity3052 likely benefit from protocols that have high doses of @entity8253 , @entity2879 , and @entity2592 during induction, as well as from protocols comprising cumulative high doses of @entity2592 and @entity2879 .
