New Aspects for Future Stratifications In Paediatric AML: Outcome According to Cytogenetics of 386 Patients Enrolled In Study AML-BFM 2004
Authors: Neuhoff Christine von , Sander Annette , Bradtke Jutta , Roettgers Silja , Teigler-Schlegel Andrea , Zimmermann Martin , Ohlendorf Johanna , von Neuhoff Nils , Creutzig Ursula , Reinhardt Dirk 
Published: October 2019

Abstract
Abstract 2741
Cytogenetic analyses are essential for stratification and prognosis in childhood AML. We analysed the frequency of chromosomal aberrations and the outcome according to the cytogenetic findings in 386 patients with data (92%) out of the total group of 422 German patients in study AML-BFM 2004. The aim was to evaluate the prognostic impact of specific chromosomal aberrations in a large cohort of patients treated according to this BFM protocol.
Patients were <18 years of age and were diagnosed between 2004 and 2009. According to the AML-BFM risk criteria based on morphology, genetics and response on day 15 of therapy, patients were assigned to a high-risk (HR) and a standard risk (SR) group.
Cytogenetic and FISH analyses-as well as RT-PCR if indicated-were performed according to standard protocols on bone marrow or peripheral blood prior to therapy.

Results:
the number of patients in different karyotypic groups and their outcome are given in the table below:
SE = standard error, pOS = probability of overall survival, pEFS = probability of event-free survival, CIR = cumulative incidence of relapse at 5 years
All patients with t(15;17) and/or PML/RARα fusion gene are surviving disease free, except for two patients who died during the first two weeks of treatment. It is noteworthy that all children with inv(16) and/or CBFβ/MYH11 fusion gene are surviving (pOS=100%).
Compared to the results of study AML BFM 98, outcome of patients with MLL-rearrangements was significantly higher in study AML BFM 2004 (pEFS 35%, SE 5%, vs. pEFS 55%, SE4%) which may be due to more intensive treatment with liposomal daunorubicin (L-DNR) and 2-chlorodeoxyadenosine (2-CDA). Patients with the translocation t(9;11)(p22;q23) and/or the MLL/AF9 fusion gene [n=43] had a pEFS of 60% (SE 9%) and a pOS of 80% (SE 6%), whereas patients with translocation t(10;11)(p12;q23) and or the MLL/AF10 fusion gene [n=13] showed a poor outcome with a pEFS of 23% (SE 13%) and a pOS of 59% (SE 14%). Based on a literature review we defined a very-high-risk group (see definition in the table) which showed a very poor outcome both in study AML BFM 2004 (n=16, pEFS 30%, SE12%) and AML BFM 98 (n=22, pEFS 14%, SE 7%). In this very high risk group 25 patients of both studies achieved first complete remission (1st CR); 11 of them underwent allogeneic stem cell transplantation (SCT) (pEFS 52%, SE16%), 14 patients did not (pEFS of the 12 patients who had an EFS of at least 0.44 years: 13%, SE 11%), Mantel-Byar p=0.17).

Conclusion:
Our results confirm the favourable prognosis for patients showing the rearrangements t(8;21), t(15;17) and inv(16) and the unfavourable prognosis for those with complex karyotypes (3 or more chromosomal aberrations), deletions in 12p and t(10;11)(p12;q23). According to these results stratification of patients in further AML BFM studies will be even more differentiated, and patients of a genetically defined very high-risk group will have an indication for SCT in 1.CR.

Disclosure:
No relevant conflicts of interest to declare.