Serum hypoalbuminemia is an independent prognostic factor in Chronic Myelomonocytic Leukemia (CMML),

CMML is a heterogenous myelodysplastic/myeloproliferative neoplasm (MDS/MPN) sharing both diseases' molecular and clinical phenotypes. Several models are used to risk-stratify patients diagnosed with CMML. Inflammation plays a pivotal role in developing the disease or its progression and has been linked to worse outcomes. Serum albumin (SA) is an inflammatory marker and/or surrogate for co-morbidities. While the role of SA has been investigated in myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), multiple myeloma, and other cancers, its prognostic value in CMML remains unclear. We identified 919 patients diagnosed with CMML with known SA levels at the time of diagnosis or prior to any therapy. We divided patients into three groups based on SA levels: < 3.5 g/dL, 3.5–4.0 g/dL and > 4.0 g/dL. We then compared the baseline characteristics and outcomes of these three groups. Patients with SA < 3.5 g/dL had higher risk disease according to the CPSS-Molecular model, WHO 2022 classification, and FAB classification. Additionally, patients with SA < 3.5 g/dL had a higher median blast percentage, ferritin levels, WBC, and monocyte count (P < 0.001). These patients were also more likely to be cytopenic and RBC transfusion-dependent (RBC-TD) (P < 0.001). In multivariable Cox regression analysis, SA was independently significant for predicting overall survival (OS) after adjusting for CPSS-Molecular risk, WHO 2022 subtype, proliferative CMML (FAB classification), RBC-TD, and bi/pancytopenia. Therefore, SA is an independent prognostic factor for OS among patients with CMML. Low SA may reflect inflammatory disease status or a surrogate for co-morbidities. Risk stratification models should incorporate serum albumin levels to refine their prognostic value.