Haematological malignancy Flashcards
What is polycythaemia?
An abnormally increased concentration of haemoglobin in the blood
Can be primary or secondary
What are the causes of polycythaemia?
Primary
- Polycythaemia ruba vera
Secondary
- High altitude
- Chronic lung disease
- Cyanotic heart disease
- Ectopic EPO
- HCC
- Burns
Pathophysiology of polycythaemia rubra vera?
Haematological malignancy
A mutation in a single haemopoietic stem cell resulting in myeloproliferation of RBCs, neutrophils, platelets
Clinical presentation of polycythaemia rubra vera?
Incidental finding on bloods
Thrombosis: stroke, MI, DVT, PE
Pruritus (with heat)
Erythromelalgia
Splenomegaly
When do patients often present with polycythaemia rubra vera?
Over 50 years
Investigations of polycythaemia rubra vera?
What would they show?
FBC:
- raised Hb, WCC, platelets
- low ferritin
Bone marrow biopsy: hypercellular
CT/MRI: splenomegaly
Which blood tests would help you differentiate between primary and secondary polycythaemia?
FBC:
- Primary: raised Hb, WCC, platelets
- Secondary: just raised Hb
Serum EPO:
- Primary: low (trying to compensate for the excess cells)
- Secondary: high (something is causing raised EPO levels, ectopic, or poor perfusion)
Management of polycythaemia rubra vera?
Thromboprophylaxis
Venesection
Anti-histamines
Hydroxyurea
What is myelofibrosis/
A rare bone marrow cancer
Proliferation of an abnormal clone of haemopoietic stem cells in the bone marrow resulting in fibrosis, replacement of bone marrow with scar tissue
There is also myeloid metaplasia
What is myeloid metaplasia?
Extramedullary haemopoiesis
In the spleen, liver and more
What causes myelofibrosis?
Primary: just happens
Secondary: to polycythaemia, leukaemias, lymphomas, multiple myeloma, infection (HIV, TB), radiation
Clinical features of myelofibrosis?
Anaemia
Leukopenia or leukocytosis (opportunistic infection)
Thrombocytopenia or thrombocytosis (bleeding tendency)
Constitutional: malaise, night sweats, low grade fever, weight loss
Extramedullary haemopoiesis:
- hepatosplenomegaly
- spinal cord compression, focal neurological deficit
- ascites
- haematuria
Progressive marrow failure, dyspnoea, abdo pain, bone pain
Investigations of myelofibrosis? What would they show?
FBC: anaemia, thrombocytopenia (or osis), leukopenia (or cytosis)
Signs of DIC
Peripheral blood film: teardrop poikilocytosis
Bone marrow biopsy: fibrosis
MRI: to look at marrow
Cytogenetic studies: especially looking for JAK mutations
Management of myelofibrosis?
Allogenic stem cell transplant is only chance at cure
Palliative
Hydroxyurea helps with splenomegaly, leukocytosis and thrombocytosis
Biologic drugs against JAK (mutation)
What is the difference between allogenic and autologous bone marrow transplants?
Autologous: patient’s own cells, taken from patient and frozen before transplant conditioning
Allogenic: donor stem cells which match patient’s HLA
What is meant by transplant conditioning?
Preparing a patient for bone marrow transplant
It’s the giving of high dose chemo or radiation to eradicate the malignancy
(This causes irreparable damage to stem cells, hence the transplant)
Which leukaemia can myelofibrosis transform to?
Acute myeloid leukaemia
What does poikilocytosis mean?
Variable shaped RBCs
They can be pencil shaped: iron deficiency
They can be tear-drop shaped in myelofibrosis
What’s the difference between lymphoma and leukaemia?
They’re both cancers of haemopoietic stem cells
In leukaemia cancer cells are in bone marrow
In lymphoma the cancer cells are in the lymph nodes or other tissues
Types of lymphoma? How are they differentiated?
Which is more common? Which is worse?
Hodgkin’s: Reed-Sternberg cells present
Non-Hodgkin’s: no Reed Sternberg cells, more common, more likely to disseminate
What are Reed-Sternberg cells?
Mutli-nucleated giant cells
Seen in Hodgkin’s lymphoma but not in Non-Hodgkin’s
What subtypes of Non-Hodgkin’s lymphoma are there?
B cell (90%) and T cell types
- Burkitt’s lymphoma
- MALT lymphoma
These are B cell lymphomas
Who gets Hodgkin lymphoma? What are some risk factors?
15-30 years
EBV
HIV
Smoking
What are the symptoms of both types of lymphoma?
Painless lymphoid swelling
- often supraclavicular in HL
- peripheral in NHL
Cough, SOB Fatigue Fever Night sweats Pruritus
Investigations of lymphoma?
FBC
- anaemia
- WCC
ESR: the higher the worse prognosis
HIV test
Lymph node biopsy: look for Reed Sternberg cells
CXR, CT to look for other affected lymph nodes and staging
Bone marrow biopsy for staging
How are H and NH lymphoma staged?
Ann Arbor
Stage I to IV
Subscript letters represent extralymphatic involvement
Management of HL?
Chemoradiotherapy
They need pneumococcal and influenza vaccines
Complications of Hodgkin’s lymphoma?
Leukaemia (from the chemo)
Solid tumours (from the chemo and radiotherapy)
Melanoma
Pancreatic Ca
Hypothyroidism
Cardiovascular disease
Who gets Non-Hodgkin lymphoma? What are some risk factors?
Middle aged people
EBV Hep C Toxins Autoimmunity H pylori
What is Burkitt’s lymphoma?
Pathophysiology?
Who gets it?
Clinical features?
B cell, from a mutation
Children
Immunosuppressed: HIV, immunosuppressing drugs
Affects ileocaecal region
Abdominal mass and obstruction
Jaw and thyroid swellings
CNS involvement
What is MALT lymphoma?
Pathophysiology?
Who gets it?
Clinical features?
Cancer of mucosa associated lymphoid tissue (commonly in stomach)
But any mucosal site can be affected
Women over 60
Dyspepsia, nausea gastric bleeding
Investigations of Burkitt’s lymphoma?
What about MALT lymphoma?
Burkitt’s: BMA, LP
MALT: endoscopy + gastric biopsy, CT
Management of NHL?
Multi-chemotherapy (r-CHOP)
What does r-CHOP stand for?
A combintation of chemotherapy drugs
Rituximab Cyclophosphamide Hydroxydaunorubicin Oncovin (Vincristine) Prednisolone
Management of Burkitt’s and MALT lymphoma?
Burkitt’s: Multi-chemotherapy
MALT: H pylori eradication, chemotherapy if advanced
What is leukaemia?
Malignancy of haempoietic stem cells
Resulting in overproduction of abnormal white cells
Diffuse replacement of bone marrow with these abnormal cells
Supression of production of normal blood cells
What 4 types of leukaemias are there?
Acute myeloid
Acute lymphoblastic:
Chronic myeloid
Chronic lymphocytic
Clinical presentation of leukaemias?
Acute: within weeks
Chronic: months - years
Bone marrow failure:
- neutropenia: infections
- anaemia: fatigue, pallor, palpitations, SOB
- thrombocytopenia: bleeding, epistaxis, menorrhagia, bruising
Also
- lymphadenopathy
- hepatosplenomegaly
- bone and joint pain
- persistent fever
- weight loss
Who is affected by each type of leukaemia?
AML: older people
ALL: children, esp under 6
CML: older people
CLL: older people
Which type of leukaemia is associated with the philadelphia chromosome?
CML
What investigations would you do for leukaemia?
FBC:
anaemia, leukopenia, thrombocytopenia
Lactate dehydrogenase and uric acid raised (due to high cell turnover)
Blood film: blast cells visible
CXR: may show pneumonia, heart disease, mediastinal mass, lytic bone lesions
Bone marrow biopsy
Immunophenotyping
Cytogenic studies
What are the differences in chronic and acute leukaemias?
Onset:
- acute = weeks
- chronic = months-years
Cells:
- acute = immature cells
- chronic = more mature cells
What are risk factors for leukaemia?
Age (in all but ALL)
Cytogenic abnormalities
Trisomy 21 (ALL, AML)
Aplastic anaemia, myelodysplastic disorder (AML)
Exposure to radiation and toxins, chemotherapy
High cell turnover causes raised levels of what in the blood?
Lactate dehydrogenase
Uric acid
What is needed in blood or bone marrow for a diagnosis of leukaemia?
Over 20% blasts in peripheral blood or bone marrow
Management of leukaemia?
Multi-chemotherapy
+ methotrexate (ALL)
In CML give imatinib
Bone marrow transplant (allogenic or autologous)
Which leukaemia is treated with imatinib?
What type of drug is it?
CML
A biologic: a tyrosine kinase inhibitor
What is multiple myeloma?
Malignant proliferation of plasma cells
Resulting in overproduction of a monoclonal antibody
And diffuse bone marrow infiltration causing bone marrow failure
How are myelomas classified?
What’s the most common?
By the type of antibody produced
IgG is most common
Clinical features of multiple myeloma?
Bones:
Pain
Pathological fractures
Spinal cord/nerve root compression
Anaemia
Leukopenia
Thrombocytopenia
Cardiac failure
Impaired renal function
Hypercalcaemia
Fatigue, nausea, constipation, dehydration
Hyperviscosity syndrome
What are the symptoms of hypercalcaemia?
Bones (pain)
Stones (renal)
Abdominal groans (constipation)
Psychic moans (confusion)
Why does multiple myeloma cause bone problems?
Imbalanced bone remodelling
Osteoclast actvity increased, osteoblast activity reduced
So lytic bone lesions
Fractures
Why does multiple myeloma cause hypercalcaemia?
Because of bone breakdown
Osteoclast activity increased, osteoblast activity reduced
Why does multiple myeloma cause renal problems?
Accumulation of the immunoglobulins in the kidneys
What is hyperviscosity syndrome?
Symptoms caused by an increase in viscosity of blood
Headache
Visual disturbance
Seizures
Cerebrovascular events
Investigations of multiple myeloma?
FBC, ESR, U+E
Plasma viscosity
Electrophoresis: serum (shows which immunoglobulin) and urine (look for Bence Jones’ protein)
XR: lytic bone lesions
Bone marrow aspirate and biopsy
What is Bence Jones’ protein?
A monoclonal globulin protein or immunological light chain
Found in urine in multiple myeloma
Management of multiple myeloma?
Incurable
Chemotherapy
High dose steroids
Allogenic stem cell transplant
Bisphosphonates and pain killers
A patient with CLL suddenly become acutely unwell, what could have happened?
Richter’s transformation: transformation to a high grade B cell lymphoma
Warm autoimmune haemolytic anaemia: haemolysis occuring at high temperatures
A patient with CML becomes suddenly acutely unwell, what could have happened?
Transformation to AML or ALL (less common)
