How the ASH Clinical Practice Guidelines Aim to Improve Myelofibrosis Management

At the 2025 American Society of Hematology (ASH) Annual Meeting, Brady L. Stein, MD, MHS, chaired a session introducing the forthcoming ASH Clinical Practice Guidelines on Myelofibrosis—the first ASH-supported guidelines developed for this rare myeloproliferative neoplasm. For clinicians who were unable to attend the meeting or who missed the session, Dr. Stein discusses the scope of the guidelines, key recommendations, evidence gaps, and what practicing hematologists can expect as the guideline manuscript moves toward publication.

Key Highlights

• The 2025 ASH session introduced the first ASH-supported clinical practice guidelines for myelofibrosis (MF), covering 6 of 10 key recommendations including JAK inhibitor use, anemia management, transplant timing, diagnostic testing, and more.

• All 10 recommendations are conditional due to low-certainty evidence, underscoring significant research gaps in MF and highlighting the need for future studies to inform stronger guidance.

• The guidelines aim to support practicing hematologists who may see only a few MF cases, offering evidence-based direction on common clinical challenges rather than proposing practice-changing or controversial recommendations.

Additional Resource: American Society of Hematology. Myelofibrosis: Clinical Practice Guidelines. Hematology.org. https://www.hematology.org/education/clinicians/guidelines-and-quality-care/clinical-practice-guidelines/myelofibrosis. Accessed December 15, 2025.

Brady L. Stein, MD, MHS: This session was an introduction to the first guidelines that have been supported by ASH for the treatment of myelofibrosis. At our session, we introduced 6 of the 10 guidelines. For the purposes of time, we weren’t able to discuss the other 4 guidelines.

The guidelines will focus on diagnostic testing, JAK inhibitor use, management of anemia, transplant strategies, use of aspirin, and iron chelation.

These guidelines just finished their period of public comment. The next step is step is to draft the manuscript. It's anticipated that we would submit that manuscript in early 2026, probably the end of the first quarter of 2026.

The best place to look for the guidelines would be on the American Society of Hematology website. There'll be different formats for including visual summaries, pocket guides, teaching slides, and the full manuscript, which would be the most comprehensive way to look at the guideline.

Consultant360: What were the most notable evidence gaps the panel encountered while developing these guidelines?

Dr Stein: Interestingly, the guidelines turned out to expose some evidence gaps rather than necessarily fill them. The evidence base for each of our questions was lower certainty compared to higher certainty.

I think the guidelines, in a way, set a future research agenda. There's a lot more questions that need answers. This was not an unanticipated finding for us.

Consultant360: Symptom assessment seems to be a major theme in the guidelines. Can you elaborate on how symptoms factor into treatment decisions?

Dr Stein: Yeah, absolutely. We focus on impact of symptoms for sure.

For example, one question had to do with treating a patient who has a higher risk presentation but is relatively asymptomatic. Another question was asked in the opposite way. We have a lower risk presentation, but a more highly symptomatic patient. The suggestion is to treat more based on symptoms rather than a risk score.  The other recommendation regarding a higher risk asymptomatic patient was more challenging. real issue with that question is we could find almost no evidence whatsoever. We found minimal studies. Part of that had to do with inclusion criteria in clinical trials for the JAK inhibitors. All of the registration studies included higher risk symptomatic patients. So, when you look at the question, it was asking about a group that was not included in clinical trials. I think people might be scratching their heads at that. Our guidelines are very evidence-based, so we have to look at the quality of the evidence, and the guidelines are strongly based on what the literature review presented to the panel. And so that recommendation really came from a lack of evidence. So that's one of our trickier ones.

Consultant360: Once these guidelines are published, do you anticipate any practice-changing recommendations?

Dr Stein: That's a great question. Is there any guideline that we're presenting that would be counterintuitive or practice changing or kind of turning the field around compared to what the field had done before? No, I don't think there's going to be anything that would be considered highly controversial or dramatically changing how we practice.

I'm hoping that what we've come up with a foundation to navigate common clinical conundrums and help navigate routine clinical practice. We hope the guidelines this is a help clinicians address common, practical clinical concerns for a group of patients that maybe overall represent a smaller proportion of patients in their clinical practice.

Consultant360: Is there anything else clinicians should know about the guideline development process or the upcoming publication?

Dr Stein: We're really thankful that the American Society of Hematology supported this project. It could not be done without them. We had an excellent panel. We're not allowed to identify panel members until publication, but I would like to acknowledge the panel. This was definitely a team effort. Again, we had 22 other members, including myself. We had people who are earlier in their career, people who are transplant specialists, people from all over the United States, people from Canada, people from abroad. And I think a lot of the heavy lifting was done by our methodology team, which is something I found unique about these guidelines. I've been involved in other guideline processes, and have learned from both experiences.  This is not a competition. It's not that one is trying to be better than the other. I think our guidelines are actually going to be relatively consistent in terms of the recommendations that are out there from other guideline groups. But the part that is most unique is that there's such a strong methodological basis to these guidelines

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