Cancer Cell Int 2019 4;19:83. Epub 2019 Apr 4.
1Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
Background: In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone.
Method: At baseline, 98 patients were tested for , , and for expression; 31 for , , , , -, , -, , and . The same genes have been also tested after induction and consolidation.
Results: Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of -, 38.7% of , 48.4% of -, 25.8% of - and 19.3% of . The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, -mutated, with low levels, and without . The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction > 1 log of the mutational burden, disappearance of mutations and lower expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning , an increase of its expression anticipated disease recurrence in 64% of cases.
Conclusions: We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the expression. Finally, we considered as relevant the assessment of quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity.