29th May 2023

Myelofibrosis

This is a condition characterised by progressive fibrosis of the marrow secondary to a clonal population of megakaryocytes; these cells interact with the surrounding bone marrow stroma and release pro-inflammatory and fibrotic cytokines. This causes progressive bone marrow failure, plus splenomegaly and constitutional symptoms. Pulmonary hypertension may also develop over time. The blood film may show a leukoerythroblastic picture. It can arise de novo or as a result of progression from PV or ET. Mutations in JAK2, CALR and MPL can be seen (as with ET), plus other somatic mutations are also seen in AML.

In order to make the diagnosis, a bone marrow is performed. This must show significant fibrosis and megakaryocyte proliferation without another causative explanation. A combination of this plus at least one other feature such as anaemia or splenomegaly is usually adequate. The presence of typical mutations (JAK2, CALR or MPL) is supportive.

The prognosis is variable but generally poor. Compared with PV and ET, there is a significantly higher risk of transformation to AML.

A very small minority of patients may be cured with allogeneic stem cell transplant. Many patients are either not fit enough for this or else their disease is mild, and the risk of such intensive treatment outweighs the benefit. Other treatment options include supportive care, cytoreductive therapy or newer drugs such as ruxolitinib (JAK 2 inhibitor).