Myeloproliferative disorders Flashcards
What are the causes of Polycythaemia?
Primary (PCRV - JAK2 V617F positive)
Secondary
- Over-production of erythropoietin (renal failure, Cushing’s, Phaeo, HCC, uterine myoma, cerebellar heamangioma)
- Hypoxia (chronic lung disease, pulmonary AV malformations, cyanotic CHD)
Others:
Dehydration
Smoker’s polycythaemia - carboxyhaemoglobinaemia
Polycythaemia Rubra Vera - PRICMCP
P: symptoms of hyperviscosity (dizziness, headache, blurred vision, pruritis - especially after shower (‘aquagenic pruritis), thrombosis (erythromelalgia - severe burning pain in hands/feet + redness, TIA, Stroke, MI, Budd Chiari Syndrome - hepatic vein occlusion)
R: Smoker, CLD (lung), CRF, HCC, Cushing’s, Phaeo
I: Hb count, EPO level, JAK2 kinase mutation - the patient may know. Abdominal imaging (splenomegaly)
C: myelofibrosis, leukaemia, thrombosis, Complication of treatment (e.g. if was on immunoSx agents)
M: phlebotomy (how often, how long), Aspirin, Hydroxyurea, Pruritis (anti-histamine, psoralen+UV light), IFN-alpha, Radioactive Phosphorus, Busulfan/P32 (Alkylating agent) - ASK about these to identify those at risk of developing leukaemia
C: current state / issue - is your haematologist worried about Leukaemia risk?
P: how is the patient coping with regular phlebotomy, symptoms. Insight?
Polycythaemia RV examination? (6)
Plethoric face, Cushingoid, Scratch marks
Nicotine staining and cyanosis
HTN
Chest - evidence of CLD
Abdo - Hepatomegaly (HCC must be excluded), Splenomegaly (80% of PCRV)
No UMN signs to suggest cerebellar Heamangioblastoma.
How would you establish the diagnosis of Polycythaemia RV? What is your approach to investigation?
FBC - raised Hb, WCC, PLT, Hct (ratio of RBC volume: total blood volume)
EPO level - reduced/absent in PCRV, raised in secondary.
ABG: to rule out hypoxia
JAK2 kinase mutation
If increased RBC mass, low EPO, normal PO2, positive JAK2 - strongly suggestive of PCRV.
Abdominal imaging looking for splenomegaly, hepatomegaly (if so, triplephase CT - HCC), and renal disease.
BM - look for pan-hyperplasia (in secondary, BM only shows erythroid hyperplasia)
What management options do you know of for PCRV? (4)
Aspirin to all
If high-risk of thrombosis - venesection, with aim to bring Hct <45, produce iron deficiency
Consider Hydroxyurea (or IFN-a), especially if leukocytosis is present (independent RF for thrombosis and venesection alone will not address this)
Ruxolitinib (JAK1/2 inhibitor) - in patients with phlebotomy dependent PCV who failed hydroxyurea - (reduction of spleen size + Hct control in NEJM 2015)
What is the prognosis of the diease + risk of developing Leukaemia, Myelofibrosis, thrombosis (15y risk) - what is the risk factor for Leukaemia risk? (2)
Median survival is 20 years
15 year leukaemia risk: 7%, not changed by hydroxyurea
15 year myelofibrosis risk: 7%
15 year thrombosis risk: 27%
Risk factor for Leukaemia: previous treatment with Radioactive-Phosphorus, Alkylating agent (e.g. Busulfan), P32.
What is myelofibrosis?
Is a chronic myeloproliferative disorder characterised by overproduction of megakaryocytes and bone marrow stromal cells → decreases BM reserve + extramedullary haematopoiesis with massive Hepatosplenomegaly.
What is the prognosis of myelofibrosis?
About 5 years
What are the causes of secondary myelofibrosis? (2 categories)
Any process that causes BM infiltration - malignant vs. non-malignant.
Malignant: myeloproliferative (CML/ET/PCRV), Leukaemia, Lymphoma, Myeloma, Metastatic Ca - so any cancer infiltration.
Non-malignant: infection (HIV, TB), autoimmune (SLE), renal (osteodystrophy, hyperparathyroidism)
Clinical features (3) of Myelofibrosis?
Anaemic symptoms
Night sweats and weight loss
Massive Hepatosplenomegaly from extramedullary haemopoiesis
Typical blood film and BM aspirate, BM biopsy finding in myelofibrosis?
Blood film: leukoerythroblastic film (myelocytes, metamyelocytes, nucleated RBCs) + tear-drop cells
BM aspirate: “dry” (unsuccessful)
BM biopsy: marked fibrosis and hypercellularity. JAK2 V617F mutation seen up to 50%.
What is the main complication of Myelofibrosis?
10% - transform into Leukaemia.
What is your approach to managing this patient with Myelofibrosis?
Goals: establish - symptom control, improve quality of life, assess for BM transplant.
Confirm the Dx: BM biopsy results
A: screen & treat secondary causes of myelofibrosis (infection, SLE, hyperparathyroidism, other cancers)
S: screen & treat complications - anaemia, thrombocytopaenia (bleeding), infection, depression. Allopurinol for Gout/Hyperuricaemia.
T: non-pharm
- Discuss establish goals of care with patient & loved ones - BM transplant (for prolonging life + potential cure) vs. symptoms + QOL care
- Discuss prognosis & advanced care directive
- Anaemia causes major source of impaired QOL - replace iron, B12, folate, blood transfusion.
- Infection prevention: hand-hygiene, avoiding contact, vaccination (especially if had splenectomy)
T: pharm
- Hydroxyurea: for symptomatic patients with organomegaly or thrombocytosis
- Ruxonitinib (JAK2 inhibitor) - reduces splenic volume and symptoms, no survival benefit.
- Splenectomy for painful splenomegaly or refractory cytopaenias
- Allogenic BMT
Involve GP, family and offer ongoing encouragement & support
Follow-up
- Monitor symptoms of anaemia, infection, bleeding, splenomegaly
- Monitor blood count for cytopaenia and leukaemic transformation
- Assess the need for transfusion, splenectomy, and BM transplant.
When would you recommend this patient with myelofibrosis to undergo splenectomy?
Important question because - splenectomy is associated with significant infection risk as well as serve as an important site of extramedullary erythropoiesis.
Painful splenomegaly or when transfusion requirement is becoming too frequent - e.g. >3 units of RBCs every 2 weeks - since when this happens, spleen may not be an “effective” source of RBC production.
What are the 2 common complications following splenectomy for MFS? (2)
Thrombocytosis - consider platelet phresis, hydroxyurea.
Hepatomegaly
