Myelofibrosis

Last reviewed: September 2018

Last updated: July 2018

Summary

Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders.

Primary myelofibrosis (PMF) is a chronic progressive myeloproliferative disorder with a median survival (around 5.5 years) much shorter than that of other myeloproliferative disorders. However, PMF survival is heterogeneous, ranging from <1 year to >30 years.

Leukoerythroblastosis and splenomegaly are the clinical hallmarks of PMF.

Death is usually due to bone marrow failure (haemorrhage, anaemia, or infection), transformation to acute leukaemia, portal or pulmonary hypertension, heart failure, cachexia, or myeloid metaplasia with organ failure.

Asymptomatic, low-risk patients without hyperuricaemia or a remedial cause for anaemia require no therapy.

Haematopoietic stem cell transplant is the only treatment option with a potential for cure.

Definition

Myelofibrosis is a reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterised by abnormal production of red blood cells, white blood cells, and platelets, in association with marrow fibrosis (scarring) and extramedullary haematopoiesis. [1] It can present de novo as primary myelofibrosis (PMF), a chronic progressive myeloproliferative disorder with its origin in a multipotent haematopoietic progenitor cell. The aetiology of PMF is unknown, and a specific clonal marker has not been identified. Leukoerythroblastosis and splenomegaly are the clinical hallmarks of PMF. When fibrosis in the bone marrow is due to a known diagnosis such as leukaemia, hypoparathyroidism, or drugs, it is called secondary or reactive myelofibrosis.

History and exam

Key diagnostic factors

presence of risk factors
constitutional symptoms (weight loss, night sweats, low-grade fever, cachexia, fatigue, and pruritus)
splenomegaly ± hepatomegaly
features of extramedullary haematopoiesis

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Other diagnostic factors

features of portal hypertension
symptoms of pulmonary hypertension
joint and bone pain
hearing loss
bleeding
infections

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Risk factors

radiation exposure
industrial solvents exposure
age >65 years

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Diagnostic investigations

1st investigations to order

FBC with differential
peripheral blood smear
bone marrow aspiration
bone marrow biopsy

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Investigations to consider

genetic mutation analysis (JAK2 V617F, calreticulin [CALR], MPL)
breakpoint cluster region-abelson polymerase chain reaction (BCR-ABL PCR)
chromosomal assessment in bone marrow examination
CD34+ cell count
antinuclear antibodies
rheumatoid factor titre
complement levels
Coombs' test
echocardiogram
ultrasound of suspected site
technetium 99 scan
CT of suspected site
MRI of suspected site
serum uric acid

Full details

Treatment algorithm

ACUTE

Contributors

Authors VIEW ALL 

Jerry L. Spivak, MD

Professor of Medicine and Oncology

Division of Hematology

Johns Hopkins University School of Medicine

Baltimore

Disclosures

JLS is an author of a reference cited in this topic and is a consultant for Incyte.

Acknowledgements

Professor Jerry Spivak would like to gratefully acknowledge Dr Ashkan Emadi, a previous contributor to this topic. AE declares that he has no competing interests.

Peer reviewers VIEW ALL 

John T. Reilly, BSc, MD, FRCP, FRCPATH

Professor and Consultant in Haematology

Royal Hallamshire Hospital

Sheffield

Disclosures

JTR is an author of a number of references cited in this topic.

Giovanni Barosi, MD

Director of the Laboratory of Clinical Epidemiology

IRCCS Policlinico S. Matteo Foundation

Pavia

Italy

Disclosures

GB declares that he has no competing interests.

Richard Silver, MD

Myeloproliferative Disorders Program Specialist

Department of Medicine

Division of Hematology and Medical Oncology

Weill Cornell Medical College

New York

Disclosures

RS is an author of a reference cited in this topic.

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Myelofibrosis

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

asymptomatic

symptomatic: aged <50 years and suitable for stem cell transplant

symptomatic: aged ≥50 years and suitable for stem cell transplant

symptomatic: not suitable for stem cell transplant

Contributors

Authors VIEW ALL 

Jerry L. Spivak, MD

Disclosures

Acknowledgements

Peer reviewers VIEW ALL 

John T. Reilly, BSc, MD, FRCP, FRCPATH

Disclosures

Giovanni Barosi, MD

Disclosures

Richard Silver, MD

Disclosures

Differentials

Guidelines

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