The Absolute Monocyte Count at Diagnosis Affects Prognosis in Myelodysplastic Syndromes Independently of the IPSS-R Risk Score

SIMPLE SUMMARY: The revised international prognostic scoring system (IPSS-R) represents the standard tool for prognostication in myelodysplastic syndromes (MDSs). It considers the degree of cytopenias together with the bone marrow blast count and the results of metaphase cytogenetics. Monocytes are a subgroup of white blood cells involved in host defense and tissue repair or remodelling. The goal of our study was to assess the prognostic impact of the absolute monocyte count (AMC) at the time point of diagnosis in patients with MDS. We found an IPSS-R-independent prognostic impact of the AMC, both when assessed as a continuous variable and when MDS patients with a low (<0.2 × 10(9)/L) or a higher (>0.4 × 10(9)) AMC were compared to MDS patients with an AMC of 0.2–0.4 × 10(9)/L. A low AMC was associated with a higher risk of transformation to acute myeloid leukemia. Hence, considering the AMC might help to identify MDS patients who could benefit from more intense treatment strategies. ABSTRACT: The absolute monocyte count (AMC) is associated with mortality in a variety of medical conditions. Its prognostic impact in myelodysplastic syndromes (MDSs) is less well studied. Therefore, we investigated its potential prognostic value in a cohort from the Düsseldorf MDS registry in relationship to the revised international prognostic scoring system (IPSS-R). An AMC below the population’s median (<0.2 × 10(9)/L) was associated with several adverse disease features such as lower haemoglobin levels, lower count of neutrophils and platelets, and a higher percentage of blasts in the bone marrow. MDS patients with an AMC < 0.2 × 10(9)/L had a significantly higher risk of progression into acute myeloid leukemia (AML). In a univariate, proportional hazards model the effect of the AMC as a continuous variable was modelled via p-splines. We found a U-shaped effect with the lowest hazard around 0.3 × 10(9)/L. Accordingly, an AMC within the last quartile of the population (0.4 × 10(9)/L) was associated with a reduced overall survival independently of IPSS-R, but not with the risk of secondary AML. Considering monocytopenia as a risk factor for AML progression in MDS may provide an additional argument for allogeneic transplantation or the use of hypomethylating agents in patients who are not clear candidates for those treatments according to current prognostic scoring systems and/or recommendations. Further studies are needed to assess the prognostic impact of the AMC in the context of prognostic scoring systems, considering the molecular risk profile, and to identify the mechanisms responsible for the higher mortality in MDS patients with a subtle monocytosis.