Real-World Data Link Higher Hemoglobin to Improved Survival in MDS

New real-world evidence suggests that for patients with myelodysplastic syndrome (MDS), achieving a state of "mild anemia" rather than settling for moderate levels may yield a dramatic benefit in overall survival.

According to Ira Zackon, MD, a hematologist-oncologist and senior medical director at Ontada, a retrospective study of more than 6500 patients presented at the 67th American Society of Hematology Annual Meeting and Exposition in December 2025 revealed that maintaining a hemoglobin level greater than 10 g/dL was associated with a median survival of nearly 5 years, double that of patients with moderate anemia.

The Burden of Anemia in MDS

MDS primarily affects an older demographic, many of whom have the condition for years. Among the various symptoms, anemia remains the most persistent challenge.

"MDS is a significant disease, especially as we get older...and especially for those [patients] we call intermediate or low risk," Zackon explained. "Anemia is...probably the most prominent low blood count in this disease and often requires an anemia-directed therapy. Some patients require blood transfusion support, and it has a significant impact on their quality of life."

Current clinical guidelines often dictate that transfusions are reserved for patients with hemoglobin levels below 8 g/dL, or sometimes 7 g/dL. This leaves many patients in a state of chronic, moderate anemia. Zackon’s team sought to challenge this paradigm, drawing inspiration from data on thalassemia, where maintaining higher hemoglobin levels has been shown to reduce cardiac stress and extend life.

"The question is, if we achieve a mild hemoglobin vs a moderate hemoglobin or a severe anemia, are there differences in overall survival?" Zackon posed.

Evaluating Real-World Outcomes

To answer this, researchers utilized Ontada’s electronic health record database, which covers a community-based oncology network. They identified more than 6500 patients diagnosed with MDS between 2005 and 2015 who were receiving anemia-directed therapy. The median age of the cohort was 78 years.

The study stratified patients based on their Revised International Prognostic Scoring System risk scores and serum ferritin levels, categorizing them into 3 groups based on the hemoglobin levels they achieved longitudinally, as follows:

• Mild anemia: Hemoglobin > 10 g/dL (~ 25% of patients)
• Moderate anemia: Hemoglobin 8-10 g/dL (> 50% of patients)
• Severe anemia: Hemoglobin < 8 g/dL (~ 20% of patients)

Clear Survival Differences

The results showed a stark stratification in longevity based on the depth of anemia.

"When we looked at overall survival, there was a clear difference," Zackon reported. "Those who maintained a hemoglobin greater than 10 had a median survival of 52 months, approaching 5 years. Those who were intermediate had a 25-month median survival. And then those [with more] severe anemia had a survival of only about...12 months."

Although Zackon noted that severe anemia often correlates with higher-risk disease, the study focused heavily on the intermediate-to-low-risk population, patients who are generally not candidates for stem cell transplants but require long-term treatment.

"We know that the true minority of those patients would go to an [allogeneic] transplant over the years of their disease," Zackon said. "So, we're really primarily focused on those patients who have...intermediate- and low-risk disease...to understand their outcomes better."

Rethinking Clinical Goals

These findings could prompt clinicians to reconsider good enough as a treatment goal. Currently, there is often clinical inertia regarding hemoglobin levels that hover just above transfusion thresholds.

"There's a tendency to accept, 'Okay, your hemoglobin is 9, 9.5. Maybe it's 8,'" Zackon said. "And patients begin to accept the reality of their lives and some of the limitations."

However, if validation confirms that pushing for a hemoglobin level over 10 improves survival, it could shift how therapies are utilized. "If we can validate that as an important end point in a broad database, then that could at least [drive] our goals of therapy," he added.

Beyond survival, the quality-of-life implications are significant. "It's not just overall survival... It's also quality of life, your ability to perform your daily routine and feel that you're able to be engaged in the activities you want to do without as many limitations," Zackon said.

Future Research and Validation

Zackon emphasized that this study is a "high-level inquiry" using structured data. The next steps involve digging deeper into unstructured data, such as chart abstraction, to fill in gaps regarding transfusion burden and risk stratification scores.

"We need to tease out what's biology and what's...how we're treating them in terms of making that difference," Zackon cautioned. "We'd be looking at something to validate this, and we wouldn't be looking at... a total change of clinical practice based on this [alone]."

He also highlighted the value of conducting this research within a community oncology setting, rather than purely academic centers, to capture the reality of the average patient.

"Our database is in the community oncology setting, nonacademic. So [it is] very important to add to the literature...with real-world data to fully reflect where the average patient gets their care," Zackon said.

As the treatment landscape for MDS evolves with new agents and a better understanding of the disease's genetic underpinnings, establishing clear therapeutic targets remains a priority.

"It's reasonably clear to state that patients generally perform better and feel better with a mild anemia," Zackon concluded. "What we can do medically...is really important in terms of improving their lives."

REFERENCE

Su Z, Whitesell M, Herms L, 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 a US community setting over the past 20 years. Presented at: ASH 2025; December 6-9, 2025; Orlando, FL. Abstract 2095.