<p>Anemia is very common in patients with myelofibrosis, affecting the majority of individuals at some point during the course of their disease. The severity of anemia is also negatively prognostic, but no criteria defining transfusion dependence and anemia response in patients with myelofibrosis have been adopted as a standard.</p>

Although anemia is incredibly common in patients with myelofibrosis, the definitions of anemia severity and anemia response differ between guidelines, centers, and clinical trials. This inconsistency makes it difficult to analyze data from retrospective databases and clinical trials. For example, if one person receives 6 red blood cell transfusions with a threshold of 8.5 g/dL and another person receives 5 transfusions with a threshold of 8 g/dL, is that different? Or is that the same? It is hard to say, and that is why there has been more effort to try to be more consistent with what we define as transfusion dependence.

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We are recognizing more and more that there is a gradient of transfusion dependency. There are those who have never been transfused. There are those who are transfusion receiving, getting a couple of transfusions here and there. There are those who are transfusion dependent whose hemoglobin levels are going to keep dropping without the transfusions. And then there is a group of patients who are heavily transfusion dependent and are transfused very frequently.

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Inconsistent and sometimes arbitrary lines have been drawn in trying to choose cutoff points for defining transfusion dependence. However, those cutoff points are different from patient to patient and from trial to trial. The panel responsible for the proposed 2024 International Working Group–European LeukemiaNet (IWG-ELN) response criteria for anemia in myelofibrosis has tried to come up with something practical and relatively easy to use to define transfusion dependence and responses, incorporating some of the existing criteria and definitions.

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The one thing that I am stuck on with the proposed 2024 IWG-ELN criteria is that they propose a hemoglobin cutoff of less than 11 g/dL in men for clinical trial inclusion compared with less than 10 g/dL in all patients from the 2013 IWG-ELN criteria. I think that the 2024 IWG-ELN criteria potentially shifting the hemoglobin cutoff to less than 11 g/dL in men is a bold call because, with clinical trials, you are balancing potential toxicity with potential benefit, and it would be very unlikely for, for example, a male patient with a hemoglobin level of 10.8 g/dL to have symptoms from their anemia. If a person has asymptomatic anemia, I am not sure that the ratio of efficacy to toxicity is optimal for that individual, even if they are technically eligible for the clinical trial treating anemia. So, although these guidelines err on the side of being broader and more inclusive, and they give more flexibility in clinical trial design, you must determine what a meaningful benefit is for individuals in the trial relative to the potential toxicity of the therapy.

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I think that, as we look to the future of anemia treatment in myelofibrosis, we want to move past anemia-supportive agents and continue to push toward developing disease-modifying therapies that improve anemia by changing the disease course in a deep and meaningful way. This would restore normal bone marrow function and red blood cell production.