Abstract
BACKGROUND
Anemia with chronic ineffective erythropoiesis is the most common cytopenia in MDS and often requires chronic red blood cell transfusions and/or anemia directed therapies. Transfusion guidelines and clinical practice support tolerating moderate to severe anemia. Recent data from transfusion supported thalassemia populations suggest that maintaining higher Hgb levels (>10 g/dL) improves survival, related to reduced cardiac mortality, independent of iron overload. We hypothesized that higher maintained Hgb levels may be associated with improved overall survival (OS) in MDS patients.
METHODS
A retrospective cohort study was conducted using structured electronic health record (EHR) data from 2005 to 2025. Eligible patients were adults with MDS and moderate to severe anemia (Hgb <10) at baseline. The index date was defined as the start date of anemia directed medial therapy. Patients were stratified into three Hgb groups based on their median value of the Hgb (g/dL) levels post the index date: <8 , 8–10 and >10. Baseline characteristics included age, sex, race and standard categories of Revised International Prognostic Scoring System (IPSS-R) risk. Median OS with 95% confidence intervals (CI) were estimated using Kaplan-Meier method, stratified by serum ferritin (<1000 or ≥1000 ng/mL) and available IPSS-R in a sensitivity analysis.
RESULTS
The study cohort included 6,533 MDS patients. The median (interquartile range) age at baseline was 78 (72, 84) years, with 46.0% female. Female patients were more prevalent in the >10 g/dL group (53.9%) compared to the <8 g/dL group (36.1%). Racial distribution was predominantly White (87%), followed by Black (9%) and Other (4%) with no significant differences (P=0.33) across Hgb groups. Among the 1,133 patients with available IPSS-R data, 46.0% were classified as low/very low risk, 35.8% as intermediate risk, and 18.2% as high/very high risk. Median OS varied significantly by Hgb group. Patients with longitudinal Hgb >10 had a median (95% CI) OS of 54.1 (51.0–57.9) months, compared to 25.2 (24.2–26.9) for those with Hgb 8–10, and 12.7 (11.4–14.0) for those with Hgb <8. At 12 months, survival rates were 89.6% for Hgb >10, 72.1% for Hgb 8–10, and 51.8% for Hgb <8. These differences persisted across all time points up to 72 months, where survival was 38.2%, 16.3%, and 5.9%, respectively. When stratified by IPSS-R score alone, median survival was 15.9 (14.0–21.3) months for high/very high risk, 25.9 (21.8–29.0) for intermediate risk, and 47.4 (41.1–53.2) for low/very low risk groups. Median overall survival by Hgb group showed a consistent trend across IPSS-R groups. Among patients with high/very high risk, survival was 57.8 (27.5–90.1) months for Hgb >10, 15.8 (13.5–22.0) for Hgb 8–10, and 11.8 (5.4–15.3) for Hgb <8. In the intermediate-risk group, survival was 59.4 (45.5–88.3) months for Hgb >10, 24.1 (21.0–28.2) for Hgb 8–10, 14.0 (8.9–16.5) for Hgb <8. For low/very low risk patients, survival was 53.2 (37.7–64.2) for Hgb >10, 50.5 (42.1–57.0) months for Hgb 8–10 and 28.1 (20.2–39.4) for Hgb <8. When stratified by ferritin level, overall median OS was 32.9 (31.1-34.5) months for ferritin <1000 and 24.9 (23.1, 26.8) months for ferritin≥1000. For Hgb <8, median OS was 10.2 (8.8, 12.2) for ferritin <1000 and 16.4 (14.6, 19.1) for ferritin ≥1000. For Hgb 8-10, median OS was 27.7 (25.7, 29.4) for ferritin <1000 and 28.4 (25.6, 30.5) for ferritin ≥1000.
CONCLUSIONS
In this large real-world cohort of patients with MDS using EHR data spanning two decades, higher maintained hemoglobin levels (>10 g/dL) were strongly associated with improved OS, independent of IPSS-R risk stratification. When stratified by serum ferritin, inferior OS in both moderate and severe maintained anemia was independent of possible iron overload, which is hypothesis generating as to the potential benefits of maintaining mild anemia as a goal of medical and perhaps transfusion therapies with optimal iron chelation. Limitations of our data include the structured data not capturing transfusion burden, allogeneic hematopoietic stem cell transplantation events (historically for only a minority), or cause of mortality. Further research is needed to explore these observations in more depth.
