Haematological Malignancies Flashcards
Where can haematological malignancies arise from?
Bone marrow
Thymus
Peripheral lymphoid system
What is an acute haematological malignancy?
Those that appear and progress over a short time scale (days/weeks)
What kinds of cells are usually present in an acute haematological malignancy?
Morphologically immature cells (blasts)
When should an acute malignancy be treated?
Immediately!
What is the time scale for chronic haematological malignancies?
After they appear they may stay stationary or progress over a longer timescale (months-years).
What do chronic haematological malignancy cells look like?
More difficult to distinguish from normal cells morphologically
What are the 2 main types of acute leukaemia?
Acute myeloid leukaemia and acute lymphoblastic leukaemia
Are there other types of acute leukaemia?
Mixed or undifferentiated
What is the incidence of ALL and AML in the UK?
Approx 1000 new cases of each per year
Who does AML affect?
People of all ages
Who does ALL affect?
Most common malignancy in childhood, but does affect adults also
What happens in ALL?
Proliferation of lymphoid blasts (B or T cells)
What symptoms do pts with ALL present with?
Symptoms of pancytopenia
Bone pain
What are the symptoms of pancytopenia?
Tiredness/fatigue/breathlessness (anaemia)
Abnormal bruising/bleeding (thrombocytopenia)
Infections (Leukopenia)
What features may be seen on examination of a patient with acute lymphoid leukaemia?
Lymphadenopathy
Hepatosplenomegaly
What symptoms do pts with AML present with?
Symptoms of pancytopenia
What is the first phase of therapy for acute leukaemia?
Inducing remission by aiming to reduce or eradicate leukaemic cells from the bone marrow
Define remission from acute leukaemia.
Normal FBC and less than 5% blasts in the bone marrow.
How many AML pts under 60 achieve remission?
80%
Aside from chemo, what can we potentially do for acute leukaemia?
Allogenic stem cell transplant (depending on risk group)
Palliative or supportive care, depending on pt needs
How many children with ALL are cured?
80%
What are the characteristics of chronic myeloid leukaemia?
Chronic myeloproliferation -> increase in neutrophils and their precursors, with increased cellularity of the marrow
What genetic change is associated with CML?
t(9;22) -> BCR-ABL gene
What is the 22nd chromosome also known as?
The Philidelphia chromosome
What is the aetiology of CML?
Unknown haha lol
Who does CML affect?
People of all ages with a peak between ages 24-45
When do CML pts usually present?
In the chronic phase
What are the most common presenting symptoms of CML?
Weight loss Night sweats Itching Gout Left hypochondral pain
What are the rarer symptoms of CML, and what causes them?
Visual disturbance
Priapism
Headaches
Caused by hyperviscosity
On examination of a CML pt, what will you find and in how many pts?
Splenomegaly in 90%
What are the lab findings associated with CML?
Neutrophilia Prominent basophils Abnormal platelets May be anaemic Raised uric acid
What can CML turn into and why is that bad?
Acute leukaemia, and because it can cause death
How can we predict outcome of CML?
Stage based on age, spleen size, blood blast cell and platelet count
What symptoms of CLL develop as the disease progresses?
Fatigue and SoB
Lymphadenopathy
Enlarged liver and spleen
Infection
How do we treat CML in the chronic phase?
Imatinib or other tyrosine kinase inhibitors
Allogenic stem cell transplantation
What can we do to treat the high uric acid associated with CML?
Allopurinol
What is essential thrombocythemia?
Chronic proliferation of platelets
How does essential thrombocythemia present?
Arterial/venous thrombosis
Splenomegaly
What can essential thromocythemia turn into?
Myelofibrosis
Can have leukaemic transformation over 2 years
What is polythaemia rubra vera?
Uncontrolled production of red cells (despite erythropoietin production being switched off), alongside other cell type production increases
What is lymphoma?
Cancer of the B and T cells i.e. clonal proliferation of lymphoid cells
What are the 2 main types of lymphoma?
Hodgkin and Non-Hodgkin
What are the 2 types of Non-hodgkin lymphoma?
High grade and low grade
What is low grade lymphoma like?
Generally viewed as incurable but not an immediate threat to life
What is high grade lymphoma like?
Immediate threat to life so need urgent chemo, but it has a good cure rate (~70%)
Which areas are affected in lymphoma?
Lymph nodes
Spleen, bone marrow, and some other areas can be involved
How can lymphoma be classified?
Descriptive Immunophenotype Cytogenic markers Morphology Site/cause of disease
How can lymphoma present?
In many different ways
Generalised enlargement of lymph nodes, weight loss, fevers, night sweats, and local masses causing symptoms
How is lymphoma diagnosed?
Histological examination of a biopsy specimen
What is the incidence of lymphoma?
Increases with age, and increasing in general
What is Hodgkin lymphoma?
Lymphoma characterised by presence of Reed-Sternberg cells (multinucleated giant cells)
What is the M:F in Hodgkin lymphoma?
2:1
WRT HL and lymphocytes, what type has the better prognosis?
Lymphocyte rich HL
How is HL treated?
Depends on stage and symptoms.
Radiotherapy for early stage, and bulky localised/resistant disease.
Combination chemo for more progressed disease.
Who does Non-Hodgkin lymphoma affect?
Pts of all ages
What is the aetiology of Non-Hodgkin lymphoma?
Environmental: -EBV causing Burkitt lymphoma -H. pylori causing gastric lymphoma Auto-immune disease Immune suppression
What are the other causes of neutrophilia?
- Infection
- Inflammation
- Drugs e.g. steroids, adrenaline, toxins, GCSF
- Myeloproliferation e.g. CML, PRV, Myelofibrosis
- Solid tumours
- Cigarette smoking
- Bleeding
What are the other causes of neutropenia?
- Infection (viral)
- Drugs (anticonvulsants, antithyroid, chemo, abx)
- Immune mediated
- Bone marrow failure
What are the causes of lymphocytosis?
- Infection (EBV, CMV, hepatitis, varicella)
- Leukaemia/lymphoma
- Stress (MI, sickle cell crisis)
- Trauma and exercise
- RA
- Adrenaline
- Splenectomy
What are the malignant causes of lymphopenia?
Hodgkin’s disease
NHL
Aplastic anaemia
Myelodysplastic syndrome
Also chemotherapy
What is myeloma?
Malignant tumour of bone marrow characterised by proliferation of plasma cells causing bone destruction and bone marrow failure.
How are myelomas subclassified?
According to the type of antibody produced.
Which subtype of myeloma is most common?
IgG meloma
What is the preceding condition to myeloma?
MGUS - monoclonal gammopathy of undetermined significance.
What is the pathophsiology of myeloma?
Plasma cell proliferation leading to neoplastic transformation of plasma cells which accumulate within the bone marrow and produce a monoclonal protein that causes organ and tissue impairment.
What process causes osteolysis and hypercalcaemia in myeloma?
Imbalanced bone remodelling due to increased osteoclast and reduced osteoblast activity.
How does myeloma cause renal impairment?
Malignant plasma cells produce excess monoclonal free light chains which are excreted via the kidneys, causing AKI and tubulo-interstitial inflammation.
There may also be dehydration, amyloid deposition, hypercalcaemia, and use of nephrotoxic drugs.
How common in myeloma?
2nd most common haem cancer - incidence is 4.5-6 in 100,000 in Europe.
Tell me about the demographics of myeloma.
Median age at presentation is 70.
More common in Afro-Caribbeans than caucasians.
M>F
What are the most common ways in which myeloma presents?
Bone pain, especially backache.
Pathological fractures.
Symptoms of hypercalcaemia such as drowsiness, dehydration, constipation, nausea)
What are some less common (but still important) ways in which myeloma might present?
- Spinal cord compression
- Lethargy (anaemia)
- Anorexia
- Dehydration
- Recurrent infections
- Syptoms of hyperviscosity (hearing loss, vertigo, headaches, seizures)
- Bleeding/bruising
What is a myeloma screen?
Basic Ix to be done to screen for myeloma:
FBC (anaemia, leukopenia, thrombocytopenia)
U&Es + Creatinine (impaired renal function)
LFTs (albumin, uric acid)
ESR
Calcium and bone profile
Ig levels
Urine protein electrophoresis
Plain X-ray of problem bone areas.
What acronym can we use to remember what goes wrong in myeloma?
CRABBI
Calcium ↑ Renal impairment Anaemia Bleeding Bone lesions/pain Infection
What are the monoclonal antibodies in the urine called in myeloma?
Bence Jones proteins
What Ix can confirm a diagnosis of myeloma?
Bone marrow aspiration and trephine biopsy -> significantly raised plasma cells.
How can we survery for bone lesions in myeloma?
Whole body MRI (CT is not suitable)
Which 3 criteria are needed for a diagnosis of myeloma instead of MGUS?
- Over 10% monoclonal plasma cells in marrow
- Monoclonal protein in serum or urine
- Evidence of myeloma-related organ or tissue impairment (CRABBI)
Which Ix is used in myeloma to predict prognosis and perform staging?
Beta-2 microglobulin levels
How should myeloma be managed, generally speaking?
- Control disease
- Prolong survival
- Maximise QoL
- Emotional and psycholoigcal support
How can myeloma be managed in fit/young patients?
Induction followed by high-dose therapy with stem cell transplantation.
How can myeloma be managed in elderly pts/pts over 70?
either bortezomib, melphalan and prednisone, or lenalidomide plus low-dose dexamethasone
What maintenance therapy is recommended for younger pts with myeloma?
Lenalidomide monotherapy if they have undergone autologous stem cell transplantation.
How should pts who are in remission with myeloma be managed?
Monitored at least every 3 months to assess:
- Symptoms
- Blood tests
- Bone imaging where appropriate
If myeloma relapses, what does treatment depend on?
Performance status Comorbidities Type Efficacy and toleration of previous therapies Interval since last therapy
How do we prevent/manage the complications of myeloma?
-Bone disease - zoledronic acid/other bisphosphonates
-Consider stabilisation of bone #s or bones at risk.
-Radiotherapy for bone
pain.
-Palliation as appropriate
-Infuenza vaccine, IVIg as appropriate
-Test for long term infections (Hep B/C/HIV) before starting Rx
What is the prognosis for myeloma?
Better than it used to be, but still very variable.
Worse if present as an emergency or older pt.
Survival can be up to 10 years depending on individual.
What can we use thalidomide for in myeloma?
Reducing paraprotein levels vie anti-angiogenesis
How does polycythaemia vera present?
Fatigue, pruritus and symptomatic splenomegaly, along with an increased risk of thrombosis
In polycythaemia vera, when is the pruritis worst?
After a hot shower or bath
How does polycythaemia look on examination?
- Plethoric
- Ruddy complexion
- Splenomegaly
- HTN
How is polycythaemia vera diagnosed?
2 major + 1 minor, or 1st major + 2 minor criteria:
Major:
- HB over 185/165
- Presence of JAK2 617 F mutation or similar
Minor:
- Hypercellularity on bone marrow biopsy
- Serum erythropoietin below normal
- Endogenous erythroid colony formation in vitro
What are the differentials for polycythaemia vera wrt raised Hb?
- Volume depletion (dehydration, severe buns etc.)
- Primary polycythaemia (genetic)
- Polycythaemia secondary to chronic hypoxia, kidney disease, or paraneoplastic (erythropoietin producing tumours)
What do initial blood tests look like with polycythaemia vera?
FBC - elevated Hb, paced cell volume, WBC and platelets raised too.
Ferritin low due to increased demand for iron.
What does polcythaemia vera look like on abood film?
Plethroic phase - normal RBCs, varing degress of maturity in other cell lines
Spent phase - tear-drop cells, leukocytosis, thrombocytosis.
How is polycythaemia vera managed?
- Control cardiovascular risk with low-dose aspirin.
- Cytoreductive Rx if high risk
- Venesection to keep haematocrit below 0.45
What is polycythaemia vera at risk of transforming into?
Myelofibrosis (10%)
Acute myeloid leukaemia (5%)
What can we use to treat advanced polycythaemia vera, and how does it work?
Hydroxycarbamide to suppress erythropoiesis.
What are the myeloproliferative syndromes?
A heterogeneous group of malignant haematopoietic disorders characterised by dysplastic changes in one or more cell lineages, ineffective haematopoiesis and a variable predilection to development of AML>
What are the risk factors for myeloproliferative disorders?
- Increasing age
- Previous cancer therapy esp. radiotherapy and alkylating agents.
- Environmental toxins
- Some rarer genetic disorders
How do MPDs present?
With symptoms of anaemia, neutropenia, and thrombocytopenia.
What signs would a pt with MPDs have on examination?
- Petechiae
- Ecchymoses
- Pale conjunctivae
- Signs of heart failure
- Tachycardia
- Candidia infection
- Splenomegaly/lymphadenopathy (uncommon)
What are some important differentials to rule out in suspected MPDs?
- Other causes of anaemia (b12/folate/iron def, CKD, haemolysis)
- Other causes of neutropenia (viral infection, drugs)
- CML
- Bone marrow failure
How are MPDs diagnosed?
By excluding all other causes of cytopaenias.
How are MPDs managed?
Supportive/symptomatic Rx
High-intensity chemotherapy for otherwise fit and well pts.
What are the complications associated with MPDs?
- Complications of anaemia/thrombocytopenia/neutropenia
- Transfusion dependence
- Iron overload after transfusion
- Transform to AML
- Splenomegaly and spleen complications
What is CLL?
Chronic lymphocytic leukaemia is a malignant monoclonal expansion of B lymphocytes with abnormal lymphocytes in the blood/bone marrow/spleen etc.
How do CLL leukaemia cells appear on blood smear?
Mature and small with a narrow border of cytoplasm and dense nucleus.
How common is CLL?
Most common leukaemia in the Western world.
Who is usually affected by CLL?
People over age 80
Can CLL be inherited?
No, but there is a strong familial basis.
How might CLL present?
Insidious onset of increasing susceptibility to infection, bleeding or petechiae, tiredness and fatigue.
What are the signs of CLL?
- Local/generalised lymphadenopathy
- Splenomegaly
- Hepatomegaly
- Petechiae
- Pallor
What differentials are there for CLL?
Other leukaemias, lymphoma, or myeloproliferative disorders.
A 74 year old man comes to the GP with a 6 month history of increasing tiredness, chronic infections, and now he can feel a mass in his abdomen.
What tests should be done as leukaemia is suspected?
- FBC
- Peripheral blood smear
- Bone marrow aspirate
- Lymph node biopsy
