Influencia de los hallazgos citogenéticos y moleculares en el pronóstico y respuesta a tratamiento de pacientes con leucemia mieloide aguda

The ELN2017 stratification has proved useful in predicting the outcome for Acute Myeloid Leukemia (AML). However, some molecular determinations detailed are limited in use in our media and the karyotype remains an important factor regarding therapy. Our aim was to evaluate the predictive capacity of different cytogenetic and molecular findings on the outcome of patients with AML. Data was informative in 592 patients (pt) (from a retrospective cohort of 688pt, diagnosed in 11 Argentine centers between Jan/13-Jun/19). The overall survival (OS) concerning genetic data was different: t(15;17), 77pt, not reached (NR); CBF rearrangements, 65pt, NR; normal karyotype, 254pt, 13m, and abnormal karyotype, 196pt, 8m; p<0.001. Regarding normal karyotype, combined data according to the ELN2010 showed differences in the outcome: NPM1+/FLT3-, 26pt, NR; NPM1-/FLT3-, 102pt, 14m; NPM1-/FLT3+, 21pt, 9m; NPM1+/FLT3+, 12pt, 7m; p=0.025 (CEPBA available 62pt, no evaluable). Adverse karyotypes were heterogeneously distributed among 9 systems: 47% CECOG-SWOG-MDACC to 99% Keating-classification, and 104 (55%) with changes related to Myelodysplastic Syndromes. The CECOG-SWOG-MDACC showed superiority to differentiate between intermediate vs adverse for OS (10 vs 6m, p=0.004; HR1.6, p=0.007, Cox’s regression) and, in the limit, for those who undergone hematopoietic stem cell transplantation (HSCT) (NA vs 15m, p=0.033; HR 2.5, p=0.053). Regarding hypomethylating agents (41pt) as first line therapy none was useful to differentiate OS (9m), complete remission (CR) or best response. When chemotherapy was evaluated, the CECOG-SWOG-MDACC and ELN2010 were similar censoring (13 vs 8m, p=0.023 and 15 vs 8m, p=0.018) or not censoring at HSCT (14 vs 8m, p=0.009, and 16 vs 8m, p=0.005). However, only the first one made a difference in CR rates (73% vs 52%, p=0.023), with a tendency for any therapy (p=0.057). Finally, all findings were compared, selecting t(15;17) as reference and applying the CECOG-SWOG-MDACC: CBF HR1.6 p=0.184; normal karyotype NPM1+/FLT3- HR2.3, p=0.057; normal karyotype NPM1-/FLT3- HR4.2, p<0.001; intermediate HR5.6, p<0.001; normal karyotype NPM1-/FLT3+ HR6.1, p<0.001; normal karyotype NPM1+/FLT3+ HR9.9, p<0.001, and adverse HR8.2, p<0.001. These HRs increased when excluding HSCT, especially for FLT3+. Our results are in agreement with the favorable outcome of t(15;17), CBF rearrangement and NPM1+/FLT3- in those with normal karyotype, whereas FLT3+ was an adverse finding. Complex karyotypes, -5 and -7, according CECOG-SWOG-MDACC, were associated with shorter OS and lower CR. However, when rearr3q, 5q-, 11q23v and 17p- were also included, according to ELN2010, they account for a shorter OS in those treated with chemotherapy.