UNRAVELLING THE HIGH INCIDENCE OF ACUTE MYELOID LEUKEMIA WITH MONOCYTIC BLAST DIFFERENTIATION IN A BRAZILIAN MULTICENTER STUDY

Abstract

Background: Acute myeloid leukemia with monocytic blast differentiation (AML-MC) is a rare malignancy (5-10% incidence) with a challenging diagnosis, classified as “non otherwise specified” AML (AML NOS), unless recurrent genetic abnormalities, therapy-related or associated myelodysplasia-related changes are reported (WHO 2017). We observed a high incidence of AML-MC and aimed to assess its molecular and immunophenotypic features in a multicenter study in Brazil. Methods: 387 AML bone marrow samples (18-84 years old) from 10 Brazilian centers enrolled in International Consortium of Acute Leukemias (ICAL) Study – IC-AML2015, is in accordance Local Ethical Boards committee. From which, 149 were morphologically diagnosed with AML-MC. FLT3 and NPM1 mutations, RUNX1/RUNX1T1 and CBFB-MYH11 rearrangements, karyotype and immunophenotype were assessed. Mononuclear cells were stained with CD45, CD34, CD117, CD11c, CD64 and CD15. Cell acquisition/analysis was performed in FACS Canto II /FACS Diva software (BD Bioscience). Positivity was considered when ≥20% of the leukemic cells. Treatment consisted on 2 induction cycles (cycle 1: 3 days of Daunorubicin 60 mg/m2 and 7 days of cytarabine 200 mg/m2; cycle 2: 6 days of cytarabine 1 g/m2 twice a day) and 1 or 2 consolidation cycles (6 days of cytarabine 1 g/m2 twice a day) and/or BM transplantation. Results: AML-MC corresponded to 38.50% of cases enrolled in the study. Stratifying according to ELN2017 (without TP53 and ASXL1), 23% were Favorable, 22% Intermediate and 19% Adverse risk. 35% of patients failed Stratification or had Not Assessed Information. Molecular Assessment showed positive detections for FLT3 (17.48%), RUNX1-RUNX1T1 (2.80%), CBFB-MYH11 (8.51%) and NPM1 (23.77%). According to treatment response evalutation, complete remission CR was achieved by 49,14%, 55,8%, 53,70% and 59,46% of patients on 1st,2ndInductionof remission cycle of chemotherapy, 1st and 2sn cycle of Consolidaton of chemotherapy, and 26.37% of patients relapsed. Multiparametric Flow Cytometry (all risks) showed 39% CD34−, 61% CD34+,11% CD34−/CD117−, 13% CD117, 87% CD117+, 95% CD33+, 89% CD38+, 47% CD123+, 8% CD14+, 21% CD7+, 44% CD11b+, 19% CD56+, 29% CD13−, 2% CD19+, 27% CD64+, 74% CD11c+ 27%, CD64+CD11c+, 19% CD15+/CD133+ and 60% CD15+ cells. Among AML-NOS patients, 26% presented CD15+ and none were stratified as Favorable risk (6% Intermediate, 17% Adverse and 4% Failed Stratification). Discussion: Since AML-MC is known to be rare, accounting for 5-10% of AML cases worldwide, its high incidence in our study seemed to be odd and raised curiosity in the molecular and phenotypic context. The fact that a great number of these cases are intermediate ELN2017 risk brings up the necessity to look at them closer, since this is a challenging group when it comes to therapy decisions. Although good response to treatment was noticed, immunophenotypically CD15 expression without molecular abnormalities was more frequent in intermediate and adverse risk. These findings may direct that high rates of good treatment response and favorable outcome in these patients are more likely to be due to favorable molecular abnormalities, while expression of CD15 alone may be associated with a more aggressive disease. Knowing that, it should be of value to investigate whether CD15 could be a good prognostic marker.