Myelofibrosis Flashcards
Myelofibrosis
Overview
a myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
the resultant release of platelet derived growth factor is thought to stimulate fibroblasts
haematopoiesis develops in the liver and spleen
Myelofibrosis - Features
Features
e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
Myelofibrosis - Lab Findings
Laboratory findings
anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
Myelofibrosis - Example Question
A 70-year-old man is referred to the haematology clinic by his general practitioner with anaemia. He has experienced progressive fatigue and shortness of breath for four months. On further questioning he also describes waking up at night soaked in sweat on one or two nights per week for the last month. His weight is stable. He has a past medical history of hypertension and COPD.
On examination he is pale. His heart sounds are normal and his chest is clear.. He has no ankle oedema and JVP is not raised. His abdomen is soft and he has splenomegaly 3cm below the costal margin with no hepatomegaly.
Test results sent with him by his GP are a follows:
Hb 92 g/l Na+ 143 mmol/l Platelets 143 * 109/l K+ 3.7 mmol/l WBC 4 * 109/l Urea 7 mmol/l Neuts 2 * 109/l Creatinine 86 µmol/l Lymphs 1 * 109/l CRP 5 mg/l
Blood film: Anisocytosis with mild hypochromia. Tear drop cells. Mild thrombocytopenia with no platelet clumping.
Chest x-ray: Mildly hyperexpanded lung fields. No focal consolidation. No masses or lymphadenopathy.
Upper GI endoscopy & colonoscopy: Normal
Presence of which mutation is required to confirm the likely diagnosis?
BCR-ABL BCL2 C-MYC > JAK2 TP53
This gentleman has B symptoms, anaemia and splenomegaly in the presence of characteristic tear drops cells on the blood film, making myelofibrosis the most likely diagnosis. The British Committee for Standards in Haematology list several mutations which together with these symptoms and fibrosis on bone marrow form the diagnostic criteria. The most common of these is JAK2.
Presence of BCR-ABL is diagnostic for CML.
BCL2 and TP53 mutations are seen in diffuse large B cell lymphoma.
C-MYC mutations are seen in Burkitt’s lymphoma.
Myelofibrosis - First Line Mx
First line treatment would be hydroxycarbamide.
Interferon alpha is used for myelosuppression in myelofibrosis in the presence of thrombocytosis or leucocytosis.
Myelofibrosis - Mx: Example Question
A 65-year-old man is seen in the haematology clinic for review of test results. He has been fatigued for the last three months and has experienced night sweats. On examination he is pale with a palpable spleen 4cm below the costal margin, mildly tender on palpation. His only other past medical history is of osteoarthritis.
His results are as follows:
Hb 89 g/l Na+ 140 mmol/l Platelets 205 * 109/l K+ 4.0 mmol/l WBC 5 * 109/l Urea 5.8 mmol/l Neuts 3.6 * 109/l Creatinine 72 µmol/l Lymphs 1.2 * 109/l CRP 3 mg/l
Blood film: Anisocytosis with mild hypochromia. Tear drop cells.
CT chest/abdomen/pelvis: Splenic enlargement. No suspicious mass lesions seen. 1cm simple right renal cyst. No lymphadenopathy.
Bone marrow biopsy: Fibrosis
Which initial therapy should be used to treat this gentleman?
Chlorambucil Fludarabine > Hydroxycarbamide Interferon alpha Lenalidomide
This gentleman has myelofibrosis as evidenced by bone marrow fibrosis, tear drop cells on blood film and constitutional symptoms. He has symptomatic splenomegaly and anaemia. First line treatment for this would be hydroxycarbamide.
Chlorambucil is used in chronic lymphocytic leukaemia and non-Hodgkin lymphoma. Fludarabine is used to treat acute myeloid leukaemia. Interferon alpha is used for myelosuppression in myelofibrosis in the presence of thrombocytosis or leucocytosis. Lenalidomide is used in the treatment of multiple myeloma.
Mutation assoc with Myelofibrosis
Myelofibrosis: B symptoms, anaemia and splenomegaly in the presence of characteristic tear drops cells on the blood film
The British Committee for Standards in Haematology list several mutations which together with these symptoms and fibrosis on bone marrow form the diagnostic criteria. The most common of these is JAK2.
