9- Haematological malignancy (Myeloproliferative Disorders and Myelodysplastic Syndrome) Flashcards
myeloproliferative disorders vs myelodysplastic syndrome
Myeloproliferative disorders: These conditions occur due to uncontrolled proliferation of a single type of stem cell
Myelodysplastic syndrome: is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
myeloproliferative disorders background
- Rare group of blood cancers caused by disorders of the bone marrow- chronic proliferation of myeloid cells.
- can cause increase in: red blood cells, platelets, white cells
3 main types of myeloproliferative disorders
1) Primary myelofibrosis
2) Polycythaemia vera
3) Essential thrombocythaemia
secondary causes of myeloproliferative changes
Platelets
* Bleeding
* Iron deficiency
* Inflammation
* Infection
* Post-surgery
* Splenectomy
Red cells
* Chronic hypoxia
* Smoking
* Obstructive sleep apnoea
* Altitude
* Renal/hepatic tumours
* Congenital heart disease
*
Primary myelofibrosis is the result of proliferation of the
hematopoietic stem cells.
Polycythaemia vera is the result of proliferation of the
erythroid cell line (red blood cell)
Essential thrombocythaemia is the result of proliferation of the
megakaryocytic cell line (platelet)
Myeloproliferative disorders have the potential to progress and transform into
acute myeloid leukaemia.
myeloproliferative neoplasms/ disorders are associated with mutations in certain genes:
- JAK2
- MPL
- CALR
TOM TIP: Remember the JAK2 mutation for your exams. This can be the target of JAK2 inhibitors such as ruxolitinib.
Myelofibrosis background
- Rare blood cancer (myeloproliferative neoplasm)
- Causes scaring of the bone marrow which makes production or normal cells difficult
The result of:
1) Primary myelofibrosis
- No history of problems with bone marrow
2) Secondary
- Polycythaemia vera
- Essential thrombocythemia
Presentation
- Spleen can enlarge
- Pancytopenia
- Can transform to AML
pathophysiology of myelofibrosis
Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia).
Results in extramedullary haematopoeiesis -> splenomegaly
When the bone marrow is replaced with scar tissue the production of blood cells (haematopoiesis) starts to happen in other areas such as the liver and spleen. This is known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly. This can lead to portal hypertension. If it occurs around the spine it can lead to spinal cord compression.
Presentation of myelofibrosis
Pancytopenia
- Anaemia
–> Fatigue
–> SoB
- Thrombocytopenia (Platelets)
–> Bleeding and bruising easily
- Neutropenia
–> infection
Others
- Bone pain- fibrosis
- Gout
- Loss of appetite
- Fever and night sweat
- Pruritis
- Pain in stomach due to splenomegaly
investigations of myelofibrosis
- Bloods
o Full blood count: RBC, WBC, platelets
o Genotyping looking for JAK 2 gene changes - US of spleen and Liver
- Bone marrow biopsy
–> test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue. - MRI/CT scan
A blood film in myelofibrosis can show teardrop-shaped RBCs, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).
Management of Primary Myelofibrosis
No symptoms
Patients with mild disease with minimal symptoms might be monitored and not actively treated
- watch and wait
Allogeneic stem cell transplantation is potentially curative but carries risks.
Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.
Supportive management of the anaemia, splenomegaly and portal hypertension.
If symptoms
- Blood transfusion- anaemia
- Low dose aspirin- reduce risk of blood clots
- Allopurinol- to prevent gout
- JAK 2 inhibitors- stop growth of cancer cells e.g. Ruxolitinib
- Chemotherapy- help reduce enlargement of spleen and liver e.g. hydroxycarbamide, busulfan, melphalan
- Immunotherapy e.g. pegylated interferon- alpha
- EPO- encourage RBC production
- Radiotherapy
- Donor stem cell transplant
o Only suitable in younger, healthier patients that are in high risk group
- Splenectomy
Essential thrombocythemia
Background
- Myeloproliferative neoplasm which causes a high number of platelets
- Develops very slowly
- Can transform to AML
Pathophysiology of essential thrombocythemia
- Stem cells make too many platelets
- Increases risk of clots
- Platelets also collect in the spleen causing splenomegaly
Risk factors for essential thrombocythemia
- Any age
- Average age is 50 to 70 yo
- JAK 2 mutation
- Fx
Risk factors for essential thrombocythemia
- Any age
- Average age is 50 to 70 yo
- JAK 2 mutation
- Fx
presentation of essential thrombocythemia
Hyper viscosity
- Thrombosis (arterial/venous)
- Haemorrhage – more common if Plt count >1500
–>Black poo
–> Nosebleeds
–> Heavy periods
–Headache
- Change in vision
Fatigue
Splenomegaly- abdominal pain
Investigation for essential thombocythemia
- FBC- raised platelets (more than 600 x10^9/l)
- Genotyping- JAK2
- Bone marrow biopsy
- CXR
- US of abdomen- spleen
management of essential thrombocythaemia
Aim to reduce number of platelets
- Low risk of developing blood clots
o Low dose aspirin
- High riskof developing blood clots
o Low dose aspirin
o Oral chemo such as hydroxycarbamide
o Anagrelide
o Interferon alpha
Prognosis of essential thrombocythaemia
- Transformation to myelofibrosis
- Leukemic transformation to AML
Polycythaemia (rubra) vera background
- Uncontrolled production of RBC in bone marrow despite erythropoietin production being switched off
- A type of myeloproliferative neoplasm – blood cancer
- Most commonly caused by JAK2 mutation
- For many treatment can control PV for many years
- Complications of PV
o Myelofibrosis
o PV can transform to AML - Secondary causes
o Lung and kidney disease
Pathophysiology of polycythaemia vera
- Increase in RBC makes the blood become thicker
- Cells can collect in the spleen, causing the spleen to become enlarged
Risk factors for polycythaemia vera
- Middle aged and older people (60yo is average age)
- Can affect children and young adults
- JAK2 mutation
o In most people this mutation occurs during a persons lifetime
Presentation of PV
- Thrombosis e.g. stroke/ MI
- Viscosity symptoms
o Headache
o Drowsiness
o Transient visual disturbances - Pruritis- esp after warm bath
- Skin- plethoric complexion
- Pain in stomach due to enlarged spleen
- High BP
- Gout
investigations for polycythaemia vera
Bloods
- FBC: Raised haemoglobin (more than 185g/l in men or 165g/l in women)
- UEs
- Genotyping to look for JAK2
- EPO
CXR
Abdominal US -spleen
management of polycythaemia vera
Low risk for blood clots
- Venesection (remove around a pint)
Once a week to begin with
- Low dose aspirin
Thin blood
High risk of clots
- Venesection
- Low dose aspirin
- Chemotherapy
–> Small increase in risk of developing leukaemia
–> E.g. hydroxycarbamide
- Targeted treatment if chemo does work
–>Peginterferon alfa 2a
–> Busulfan
- Allopurinol
- Radiotherapy
Prognosis for polycythaemia vera
- Leukaemia transformation
- Myelofibrosis – 10-20% of patients after 15 years
Myelodysplastic syndrome background
is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells. There are a number of specific types of myelodysplastic syndrome.
It causes low levels of blood components that originate from the myeloid cell line:
- Anaemia
- Neutropenia (low neutrophil count)
- Thrombocytopenia (low platelets)
risk factors for myelodysplastic syndrome
It is more common in patients above 60 years of age and in patients that have previously had treatment with chemotherapy or radiotherapy.
There is an increased risk of transforming into acute myeloid leukaemia.
Presentation of myelodysplastic syndrome
Patients may be asymptomatic and incidentally diagnosed based on a full blood count.
They may present with symptoms of
- anaemia (fatigue, pallor or shortness of breath)
- neutropenia (frequent or severe infections)
- thrombocytopenia (purpura or bleeding).
investigations for myelodysplastic syndrome
Full blood count will be abnormal. There may be blasts on the blood film.
The diagnosis is confirmed by bone marrow aspiration and biopsy.
