LAUSR

sis we included 863 CBCs from the 145 patients (of the 204 original patients) with a median (range) of 4 (3-24) CBCs per individual. These CBCs accounted for 90% of the total CBCs in the entire cohort, and patient distribution according to WHO categories for the 145 patients was similar to the total cohort (Supporting Information Table 1). Overall, male patients became anemic with a median of 1063 days (IQR, 832-1393) prior to MDS diagnosis as compared to 280 (IQR, 208-316) days for women (P5 .002). Changing the lower hemoglobin threshold level to the WHO defined of 12 g/dL for women increased the pre-diagnostic anemic period to 979 days (IQR, 793-1240). When we included WHO morphology categories in the model, we observed the shortest duration of pre-diagnostic anemia in the high risk group; 1 month (IQR, 1-2) and 18 (IQR, 12-30) months in women and men, respectively (Supporting Information Figure 3). There was a clear stepwise decrease in the duration of anemia in women which was longest in the low risk group (median 29 months [IQR, 21-42]), followed by 5 months (IQR, 3-6) in the intermediate risk group and shortest in the high risk group with 1 month (IQR, 1-2). In men, we observed no significant differences between groups with duration of 35 months (IQR, 24-50), 40 months (IQR, 30-50), and 18 months (12-30) in low-, intermediate-, and high risk groups, respectively. Fifty percent of CBCs analyzed at time of MDS diagnosis exhibited macrocytosis, whereas only one percent displayed microcytosis (Supporting Information Figure 4). When combining hemoglobin and MCV measurements it also became evident that MCV was often abnormally high even when the hemoglobin concentration was within normal range (Supporting Information Figure 5). In conclusion, anemia is present years before the diagnosis of MDS. Women with intermediateand high risk MDS display the shortest duration of pre-diagnostic anemia, which may point to the existence of pathogenically different conditions with phenotypes unaffected by disease duration since the majority of patients do not seem to risk progression during the pre-diagnostic period. Many patients receive multiple blood transfusions before diagnosis emphasizing the difficulties in proper MDS diagnosis and that many patients have a prodromal phase before MDS diagnosis. Future research should focus upon early identification of the minority of low risk MDS patients at risk of progressing to high risk MDS or overt AML.