New ASH guideline refines myelofibrosis care from diagnosis to transplant

Clinical takeaway: For adults with myelofibrosis, ASH now recommends broader molecular profiling at diagnosis and a more individualized treatment approach based on symptoms, anemia, transplant eligibility, and genetic risk. The guidance also clarifies when JAK inhibitors should be used, avoided, or switched.

The American Society of Hematology (ASH) has published its first comprehensive guideline for adult myelofibrosis, including 10 evidence-based recommendations spanning diagnosis, drug treatment, anemia management, thrombosis prevention, and stem cell transplantation. The guidance aims to reduce practice variation in a rare chronic blood cancer where treatment decisions often depend on symptom burden, prognosis, and patient preferences.

One of the clearest recommendations is for expanded molecular testing at diagnosis. Rather than limiting testing to driver mutations such as JAK2, CALR, and MPL, the panel suggests extended next-generation sequencing to identify high-risk mutations that can refine prognosis and inform treatment and transplant decisions. Repeat testing may be warranted at disease progression or before transplantation.

The guideline also draws sharper distinctions around JAK inhibitor use. For lower-risk patients with symptomatic splenomegaly or disease-related symptoms, ASH suggests JAK inhibitor therapy. In contrast, the panel advises against routinely starting JAK inhibitors in higher-risk patients who lack symptoms or symptomatic splenomegaly, citing uncertain benefit and potential toxicity.

Several recommendations address anemia, a common complication of myelofibrosis and JAK inhibitor therapy. For patients whose primary disease burden is anemia, the panel supports either anemia-directed therapies or the anemia-benefiting JAK inhibitors momelotinib or pacritinib. Transfusion-dependent patients may particularly benefit from momelotinib or pacritinib, while non-transfusion-dependent patients may start with agents such as erythropoiesis-stimulating agents, luspatercept, or danazol.

For patients who develop JAK inhibitor-associated anemia, ASH recommends switching to momelotinib or pacritinib when anemia limits effective dosing of frontline therapy. If symptom and spleen control remain adequate, supportive measures such as transfusions, erythropoiesis-stimulating agents, luspatercept, or androgens can be used instead.

Transplant guidance emphasizes earlier planning. Patients with higher-risk disease who are responding to JAK inhibitors should be referred early for allogeneic stem cell transplant consultation rather than waiting until treatment failure. However, the panel advises against routine pre-transplant JAK inhibitor use in JAK inhibitor-naive patients unless substantial splenomegaly or symptoms are present.

The guideline also supports low-dose aspirin for primary thrombosis prevention in patients with JAK2 V617F-mutated myelofibrosis, while recommending individualized decision-making for other patients. Routine iron chelation for transfusional iron overload is not recommended outside select circumstances, such as transplant consideration.

“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 chair Brady Stein, MD. He added that important evidence gaps remain and should help shape future research priorities.

Key recommendations

• Perform extended molecular genetic testing at diagnosis and consider repeat testing at major clinical decision points.
• Use JAK inhibitors in lower-risk patients with symptomatic disease.
• Avoid routine JAK inhibitor initiation in higher-risk patients who are asymptomatic and lack symptomatic splenomegaly.
• Consider momelotinib or pacritinib for anemia-predominant disease, especially in transfusion-dependent patients.
• Switch to momelotinib or pacritinib when JAK inhibitor-associated anemia limits effective treatment.
• Refer higher-risk patients for transplant consultation early, even when responding to JAK inhibitor therapy.
• Use low-dose aspirin for patients with JAK2 V617F-mutated myelofibrosis if no contraindication exists.
• Do not routinely use iron chelation for transfusional iron overload.

Source: Stein BL, et al. (2026 Oct 14) Blood Adv. American Society of Hematology 2026 Guidelines for the Management of Myelofibrosis in Adults