Rural but Not Urban AML Exhibit Cytogenetic and Molecular Characteristics of Therapy-Related AML
Authors: Gruson Berengere , Ivanoff Sarah , Berthon Céline , Harrivel Veronique , Nibourel Olivier , Frimat Cécile , Preudhomme Claude , Marolleau Jean-Pierre 
Published: November 2019

Abstract
Background:There are few established risk factors for AML. Benzene, radiation, prior chemotherapy treatments for cancer, and cigarette smoking have been causally linked with AML. Few studies have shown that incidence rates are highest in the agricultural region and it has been hypothesized that farming and its related exposures (e.g., pesticides) may account for this increased risk. Nonetheless, there are no do data regarding clinical, cytogenetic and molecular differences between rural and urban area. The primary objective of this study is to look for cytogenetic features of rural patients. Secondary objectives are to search for clinical and molecular characteristics.
Patients and methods: We conducted a retrospective analysis of 521 AML patients treated in 2 french institutions (Amiens University Hospital and Lille University Hospital) between 2008 and 2013. Patients with therapy related AML have been excluded. Patient demographics as well as clinical, hematological, cytogenetics and molecular data were collected from the Nord-pas de Calais and Picardie observatory. European Leukemia Net (ELN) classification was used for cytogenetics prognosis. We geocoded addresses using the geographic information system of the french National institute of statistics and economics (INSEE, http://www.insee.fr). According to the INSEE criteria, a location of residence was defined as rural for a city of population under 2,000 inhabitants without a contiguous built area of more than 200 m. Moreover, the population was divided into quartiles according to the percentage of farm in local companies.
Results: In our population 120/521 patients (23%) lived in a rural area and 401/521 (77%) in an urban area. Sex ratio (1.6 vs 1.2, p=0.2) and median age at diagnosis (64 vs 61 years, p=0.05) were similar.
There was no difference in complete blood count (hemoglobin, platelets, leukocytes and circulating blasts levels) as well as bone marrow blasts percentage, type of AML (de novo vs post MDS or MPN) and WHO classification at diagnosis between the two groups.
Concerning cytogenetic anomalies, proportion of favorable and intermediate AML were similar between the two groups. However, there are more patients with unfavorable cytogenetics in rural area (41% vs 28%, p=0.04). Moreover, we observed more 11q23 anomalies in the rural patients group (22% vs 9%, p=0.04). Concerning molecular anomalies, rural patients seem to have less FLT3-ITD positivity (11% vs 19%, p=0.2), and CEBPAmutation (2% vs 7% p= 0.07) without significance. Overall survival was similar between the two groups.
Same results have been obtained when we compared patients depending on the proportion of farm in their area (table 1.) with more MLL anomalies (p=0.03) and unfavorable cytogenetics (p=0.005).
Conclusions:Our results showed that rural AML might present specific features. These AML would present more like therapy-related AML with more 11q23 anomalies and more unfavorable cytogenetics feature.
Abstract 2353. Table 1. Characteristics of AML according to the proportion of farm in the area Proportion of farm p %≤ 0.8 n= 144 0.8<% ≤ 3.9 n=122 3.9<% ≤ 11.3 n=128 %> 11.3 n=130 Age, median (range) 63 (61-65) 62 (60-66) 61 (56-64) 63 (61-66) 0.34 Sex ratio (M/F) 1.25 1.28 1.32 1.43 0.9 Type of AML, secondary (%) 28/136 (20) 18/109 (17) 15/116 (13) 24/124 (19) 0.4 White blood cells, 109/L 6.8 (4.5-10.8) 7.8 (4.6-14.2) 7.9 (5.6-14.4) 4.5 (3.4-7) 0.08 Bone marrow blasts, % 53 (49-60) 59 (46-66) 54 (43-62) 47 (38-56) 0.2 WHO classification, (%) AML with reccurent genetic abnomalities 32/122 (30) 26/103 (25) 26/104 (27) 21/107 (20) 0.7 AML with myelodysplasia related changes 49/122 (40) 33/103 (32) 33/104 (33) 46/107 (43) 0.8 AML NOS 42/122 (34) 43/103 (42) 39/104 (37) 39/107 (36) 0.6 Cytogenetics, (%) Favorable 35/100 (35) 27/93 (29) 29/95 (31) 22/92 (24) 0.4 Intermediate 40/100 (40) 44/92 (48) 32/95 (34) 33/92 (36) 0.2 Unfavorable 25/100 (25) 21/92 (23) 33/94 (35) 37/92 (40) 0.03 MLL rearrangement, (%) 3/78 (4) 3/63 (5) 14/79 (18) 14/82 (17) 0.005 Molecular biology, (%) FLT3 ITD 18/105 (17) 18/92 (19) 21/93 (22) 7/77 (9) 0.22 NPM mutation 31/93 (33) 22/89 (25) 24/89 (27) 13/75 (17) 0.3 CEBPA mutation 7/94 (7) 3/86 (3) 5/83 (6) 4/73 (5) 0.6

Disclosures
No relevant conflicts of interest to declare.