Primary myelofibrosis — Rapid | Doctor’s Passport

Synopsis

Recognise marrow fibrosis and extramedullary haematopoiesis, distinguish prefibrotic and secondary disease, quantify molecular risk and integrate symptom control with early curative transplant assessment.

Suspect myelofibrosis with massive splenomegaly, constitutional symptoms, anaemia, teardrop cells, nucleated red cells, left-shifted granulocytes, raised LDH or a dry marrow aspirate.
First-line assessment is FBC and expert film, reticulocytes, haemolysis, iron, B12 and folate, renal, liver, urate and LDH plus examination of spleen, liver, symptoms and thrombosis.
Confirm with bone-marrow trephine for atypical megakaryocytes and fibrosis, cytogenetics and JAK2, CALR and MPL testing; exclude BCR-ABL1 and secondary fibrosis.
Distinguish prefibrotic primary myelofibrosis from essential thrombocythaemia because marrow architecture, progression risk and treatment counselling differ.
Use DIPSS, DIPSS-plus or molecularly informed scores together with symptoms, transfusion dependence, blasts, comorbidity and transplant fitness.
Allogeneic stem-cell transplantation is the only established curative treatment and should be assessed early for suitable intermediate-2, high-risk or adverse molecular disease.
Ruxolitinib is NICE commissioned for intermediate-2 or high-risk disease-related splenomegaly or symptoms; starting dose is platelet dependent and abrupt withdrawal can cause severe rebound.
Momelotinib is NICE commissioned for intermediate-2 or high-risk disease with moderate to severe anaemia in defined JAK-inhibitor-naive or ruxolitinib-exposed adults.

Key red flags

Sudden left upper-quadrant pain, shoulder-tip pain, guarding, hypotension or haemoglobin fall with massive splenomegaly suggests infarction, haemorrhage or rupture and needs urgent imaging and surgical input.

Fever, hypotension or hypoxia with neutropenia or JAK-inhibitor therapy is sepsis until proved otherwise and needs immediate antibiotics.

New circulating blasts, rapid cytopenia, severe B symptoms or extramedullary lesions suggests accelerated or blast-phase disease and requires urgent AML-pathway assessment.

Blast transformation

Rising circulating blasts, rapid count decline, severe systemic symptoms or new tissue masses needs same-day specialist escalation.

Investigation priorities

First-line blood and reversible-cause panelFirst stepFirst line

Recognise the phenotype and identify treatable contributors to cytopenia.

Management branches

Suspected myelofibrosisConfirm architecture and clone

Leucoerythroblastosis, teardrops, splenomegaly or unexplained cytopenia suggests fibrotic marrow disease.

Assess reversible cytopenia causes, symptoms, spleen, thrombosis and prior PV or ET phenotype.
Obtain trephine with expert morphology, fibrosis grade, blasts, cytogenetics, JAK2, CALR, MPL and broader myeloid testing.
Exclude secondary fibrosis and classify prefibrotic, overt primary or post-PV or post-ET disease.

Key medicines

RuxolitinibStart orally twice daily by platelet count: 20 mg above 200 × 10⁹/L, 15 mg at 100 to 200 × 10⁹/L, 10 mg at 75 to below 100 × 10⁹/L and 5 mg at 50 to below 75 × 10⁹/L; do not start below 50 × 10⁹/L.Reduce the platelet-based start by about 50% in severe renal impairment or any hepatic impairment; ESRD dosing is post-haemodialysis only. Reduce the unit dose 50% with strong CYP3A inhibitors or fluconazole and avoid fluconazole above 200 mg daily. Monitor FBC every 2 to 4 weeks initially, infection and skin, taper when possible, and avoid use in pregnancy or breastfeeding.

MomelotinibGive 200 mg orally once daily while benefit persists; start 150 mg once daily in severe Child-Pugh C hepatic impairment, reduce toxicity doses in 50 mg steps and discontinue if 100 mg once daily is not tolerated.No renal adjustment is required above 15 mL/min, but ESRD has not been studied. Monitor FBC, liver tests, infection, neuropathy, cardiovascular events, thrombosis and BCRP substrates; avoid strong CYP3A4 inducers. Pregnancy and breastfeeding are contraindicated, and systemic hormonal contraception needs an added barrier during treatment and for 1 week after.

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