ASH Issues New Myelofibrosis Guidelines With 10 Management Recommendations

The American Society of Hematology (ASH) has released new evidence-based guidelines for the management of myelofibrosis in adults, comprising 10 recommendations that address extended molecular testing, interferon and JAK inhibitor therapy, management of myelofibrosis-associated anemia, timing of transplantation, anti-platelet therapy, and iron chelation, according to a news release from the society.¹ The guidelines, developed by a multidisciplinary expert panel using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, were published in Blood Advances.²

What do the guidelines recommend for testing and prognostication?

In all patients with myelofibrosis, the panel gave a conditional recommendation based on moderate certainty of evidence for extended molecular genetic testing, such as next-generation sequencing, compared with limited testing for the myeloproliferative neoplasm driver mutations JAK2, CALR, and MPL to help identify high-risk mutations and guide care. The panel noted that extended testing should be performed at diagnosis and may be repeated at key clinical decision points, such as disease progression, pre-transplant evaluation, or when making new treatment decisions, and that the strongest benefit is likely among patients eligible for hematopoietic cell transplantation (HCT).

“These recommendations address questions that routinely come up for clinicians and patients managing myelofibrosis, and our hope is that they will enable hematologists to more confidently deliver better care to their patients,” said guideline panel chair Brady Stein, MD, a professor of medicine at Northwestern University’s Feinberg School of Medicine, in the news release.¹ “That said, important gaps in evidence remain, and we hope the questions we asked can help set a future research agenda to further improve care for patients with this disease.”

How should JAK inhibitors be used?

The panel’s recommendations tied JAK inhibitor use to symptom burden rather than risk category alone. In JAK inhibitor–naïve populations with higher-risk overt myelofibrosis without symptomatic splenomegaly and/or disease-related symptoms, the panel gave a conditional recommendation with very low certainty against initiating JAK inhibitors, emphasizing a good practice statement for dynamic, structured symptom assessment in these patients under observation. Conversely, in JAK inhibitor–naïve populations with lower-risk overt myelofibrosis who have symptomatic splenomegaly and/or disease-related symptoms, the panel gave a conditional recommendation with very low certainty for the use of JAK inhibitors. For patients with prefibrotic myelofibrosis and no indication for cytoreduction, the panel issued a conditional recommendation with very low certainty against the routine use of pegylated interferons.

What strategies did the panel recommend for myelofibrosis-associated anemia?

For JAK inhibitor–naïve populations whose primary indication for treatment is disease-related anemia, the panel suggested either JAK inhibitor therapy with momelotinib (Ojjaara) or pacritinib (Vonjo) or non-JAK inhibitor anemia-directed therapies such as erythropoiesis-stimulating agents, luspatercept-aamt (Reblozyl), or danazol (Danocrine); this was a conditional recommendation given with low certainty. For patients who develop JAK inhibitor-associated anemia that prevents the use of an optimal dose of a first-line JAK inhibitor for symptom and spleen control, the panel gave a conditional recommendation with low certainty for switching to momelotinib or pacritinib; for those who maintain adequate symptom and spleen control despite anemia, the panel gave a conditional recommendation with low certainty for implementing anemia-optimization strategies. A good practice statement emphasized that anemia management should be guided by its timing and impact on disease control, distinguishing early-onset, often drug-related anemia from late-onset anemia that may signal disease progression.

What do the guidelines say about transplantation, aspirin, and iron chelation?

In patients with higher-risk myelofibrosis who are receiving and responding to JAK inhibitor therapy, the panel gave a conditional recommendation with low certainty for early referrals for allogeneic HCT consultation compared with delayed referral after failure of response. A good practice statement noted that patients with high-risk molecular and cytogenetic features should be prioritized for early consultation even during an optimal JAK inhibitor response.

In JAK inhibitor–naïve populations planned for transplantation, the panel issued a conditional recommendation with very low certainty against the routine use of pre-transplant JAK inhibitors except in those with marked splenomegaly or disease-related symptoms. For anti-platelet therapy, the panel gave a conditional recommendation with very low certainty for primary prevention with low-dose aspirin over no aspirin in patients with JAK2 V617F–positive myelofibrosis along with a shared decision-making process incorporating myelofibrosis subtype and thrombotic and bleeding risk factors for all other patients. Finally, in patients with overt myelofibrosis and transfusional iron overload, the panel issued a conditional recommendation with very low certainty against routine iron chelation therapy, with special considerations potentially applying for patients planned for HCT.

All 10 recommendations were conditional, and the panel identified future research priorities for each, including better prediction of which patients will benefit from specific treatments and clarification of transplant timing.

References

1. ASH issues new recommendations to improve myelofibrosis care. News release. American Society of Hematology. October 14, 2026. Accessed October 15, 2026. https://tinyurl.com/yn8279xm
2. Stein BL, Abdallah M, Abel GA, et al. American Society of Hematology 2026 guidelines for the management of myelofibrosis in adults. Blood Adv. Published online October 14, 2026. doi:10.1182/bloodadvances.2026021650