Higher Maintained Hemoglobin Associated With Improved Survival in MDS, With Ira Zackon, MD

Higher maintained hemoglobin levels have been strongly associated with improved overall survival in patients with myelodysplastic syndromes (MDS), independent of Revised International Prognostic Scoring System (IPSS-R) risk, according to a recent retrospective cohort study.1

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by Ira Zackon, MD, senior medical director of Ontada Medical Office, this study reevaluates the ideal goals of anemia management across a spectrum of hematologic diseases. Based on these data, Zackon and colleagues suggest that mild anemia may be an efficient target for medical and potentially transfusion therapies.1

“Most transfusion guidelines say not to transfuse with hemoglobin unless it’s >8 or even 7,” Zackon told HCPLive in an exclusive interview. “We allow our patients to live with moderate or sometimes severe anemia if other therapies can’t quite get there. This study is affirming, perhaps, that we need to target a hemoglobin level >10 and maintain that for optimal outcomes.”

MDS is a heterogeneous group of disorders that can lead to bone marrow dysplasia, ineffective hematopoiesis, and the potential risk of transformation to acute myeloid leukemia. For lower-risk MDS cases, survival ranges from 2 to >10 years. Additionally, many patients with low-risk MDS exhibit anemia and transfusion dependence, which intrinsically reduces health-related quality of life and correlates with shorter survival.2

Zackon and colleagues utilized electronic health record data from 2005 to 2025, including patients with MDS and moderate to severe anemia – defined as hemoglobin <10 – at baseline. Patients were then stratified into 3 hemoglobin groups based on their median value of the hemoglobin levels post index: <8, 8-10, and >10. Investigators also examined baseline characteristics, including age, sex, race, and standard categories of IPSS-R risk.1

The study ultimately included 6533 patients with MDS; the median age at baseline was 78 years (interquartile range [IQR], 72-84), and 46% of patients were female. OF the 1133 participants with available IPSS-R data, 46% were classified as low/very low risk, 35.8% as intermediate risk, and 18.2% as high/very high risk.1

During the study, median overall survival varied significantly by hemoglobin group. Patients with longitudinal hemoglobin >10 had a median overall survival of 54.1 months (95% CI, 51-57.9), compared to 25.2 (95% CI, 24.2-26.9) for patients with hemoglobin 8-10 and 12.7 (95% CI, 11.4-14) for those with hemoglobin <8. These differences remained across all time points up to 72 months, at which point survival was 38.2%, 16.3%, and 5.9%, respectively. After stratifying these by IPSS-R score alone, investigators found a median survival of 15.9 months (95% CI, 14-21.3) for high/very high risk patients, 25.9 (21.8-29) for intermediate risk patients, and 47.4 (41.1-53.2) for low/very low risk patients.1

When stratified by serum ferritin levels, median overall survival was 32.9 months (95% CI, 31.1-34.5) for ferritin <1000 and 24.9 months (95% CI, 23.1-26.8) for ferritin ≥1000. For hemoglobin <8, median overall survival was 10.2 (95% CI, 8.8-12.2) for ferritin <1000 and 16.4 (95% CI, 14.6-19.1) for ferritin ≥1000. For hemoglobin 8-10, median overall survival was 27.7 (95% CI, 25.7-29.4) for ferritin <1000 and 28.4 (95% CI, 25.6-30.5) for ferritin ≥1000.1

Ultimately, Zackon and colleagues determined that patients with MDS who exhibited maintained hemoglobin levels >10 g/dL also displayed improved overall survival, irrespective of IPSS-R risk stratification. Additionally, stratification by serum ferritin indicated that inferior overall survival in both moderate and severe maintained anemia was independent of possible iron overload, spotlighting the potential benefits of maintaining mild anemia as a goal of medical and transfusion therapies with optimal iron chelation.1

“MDS is not rare in the general patient population, especially as we get older,” Zackon said. “We’ve had limited therapy successes over time, and it’s taken time to build that up. I think we’re looking forward to more impactful therapies on the anemia side. The more that we can improve anemia, which is a primary aspect of the disease, the more opportunity we have to improve not only the longevity, but the quality of our patients’ lives.”

Editor’s Note: Zackon reports disclosures with Ontada and McKesson.

References

1. Su Z, Whitesell M, Zackon I, et al. Maintaining higher hemoglobin levels is associated with improved overall survival in myelodysplastic syndromes (MDS): A real-world retrospective analysis of electronic health records from US community settings over the past 20 years. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Kim N, Pulte ED, Ehrlich LA, et al. US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia. J Clin Oncol. 2025;43(35):3760-3768. doi:10.1200/JCO-25-01369