PB1847: ACUTE MYELOID LEUKEMIA – IS IT MORE BESIDES GENETIC ABNORMALITIES?

Abstract

Background: Acute myeloid leukaemia (AML) still carries a poor prognosis, despite novel aproaches. Age and previous myelodysplastic syndrome (MDS) are important risk factors. Environmental factors: professional benzene exposure, residential background and exposure to chemotherapy (CT)/radiotherapy (RT) have also been implicated. Aims: To evaluate environmental factors of AML patients, its genetic characteristics and overall survival (OS), in a tertiary centre. Methods: We retrospectively revised newly diagnosed AML in our centre between 2018 - 2020. Clinical and laboratory data were obtained by clinical files review Results: We included 235 patients, 47.2% (n=111) male. Median age 69 (19-97) years. (67 [28.5%]≤60 years old. – YOUNG and 168 [71.5%] with >60 years old - OLD). The most common WHO 2016 category was AML with myelodysplasia-related changes (MRC) (37.0%; n=87), followed by AML NOS (21.3%; n=50); 15 (6.4%) patients had acute promyelocytic leukaemia with PML―RARA, 21 (8.9%) therapy-related myeloid neoplasm and 17 (7.2%) post-myeloproliferative neoplasm (post-NMP) AML. The main category within YOUNG patients was AML with mutated NPM1 (19.4%) and in the OLD group was AML-MRC (45.2%). Genomic classification (GC) (Papaemmanuil, 2016) was available for 117 cases (49.8%): AML with no detected driver mutations (n=28; 23.9%); AML with mutated chromatin, RNA-splicing genes, or both (n=26; 22.2%). Considering YOUNG vs OLD patients, the main category was AML with mutated NPM1 (25%) vs AML with no detected driver mutations (32.3%). Regarding ELN risk stratification: 20.0% were low-risk, 27.1% intermediate risk and 52.9% high-risk category. OS for total cohort was 4.2 months, with 177 events (75.3% of included patients). The YOUNG patients had a median OS of 18,7 months while the OLD had median OS of 2,6 months, with P<0,001 (HR 2,31). Ninety nine (42.1%) patients lived in industrial regions. We found no correlation between living place and dysplasia, even after adjusting for age, ELN risk or GC. We found an apparent association of WHO subtype with living place (p=0.013), as post-MPN AML was more common in non-industrial (10.3 vs 3.0%) and AML with mutated NPM1 in industrial areas (11.1 vs 7.3%), but they were lost after adjusting for age. There was no OS difference between industrial and non-industrial places even after adjusting for age. Regarding professional exposure (available for 85 patients), 7.1% were exposed to benzene, 2.4% to agricultural activities and 31.8% to other chemicals, 58.8% with no significant exposure, with no differences in WHO classification, GC nor age. Smoking appeared associated with longer OS (6.6 vs 34.9%; p=0.026; HR 0.53), but this effect is lost after adjusting for age, as smoking was more common in YOUNG (65.7 vs 25.0%). There was no correlation with AML subtype or risk. Concerning other risk factors like alcohol consumption, obesity, family history of cancer, previous solid neoplasm, previous chemotherapy or previous radiotherapy none of them had impact in AML subtype, ELN risk or OS (p=NS). Summary/Conclusion: In our cohort, the majority of patients were over 60 years old and presented with AML-MRC, as described in the literature. Concerning GC, the dominant category was AML with no detected driver mutations. Looking at environmental factors, in our cohort only residential background correlated with AML subtype, despite non-significance impact in prognosis.