Flashcards in Haematological Malignancies Deck (62):
What are the types of haematological malignancies?
Based on speed of presentation: acute or chronic (depends on type and stage of defect)
Based on site: bone marrow (medullary/extramedullary) or lymph nodes (lymphoma)
based on lineage: myeloid or lymphoid
What is the most common childhood cancer?
Acute lymphoblastic leukaemia
What is the presentation of acute lymphoblastic leukaemia
marrow failure: anaemia, infections, bleeding
leukaemia effects: high WCC and involvement of extra-medullary areas e.g. CNS, enlarged lymph nodes (which can cause venous obstruction)
What age group does acute myeloid leukaemia tend to affect?
elderly - median age about 70
When are Auer Rods seen?
Blood film in Acute Myeloid Leukaemia
Why is it important to differentiate between AML and ALL?
the treatment for each is very different
What is the treatment of ALL?
Multi-agent chemotherapy - can last up to 2-3 years
different phases of treatment of varying intensity (induction, consolidation, intensification, maintenace)
targeted treatments in certain subsets
What is the treatment of AML?
between 2-4 cycles of chemo
Through what device is chemo usually administered?
How do you treat infection due to chemo (neutropenic sepsis)?
bacterial: empirical treatment with broad spectrum antibiotics (particularly covering GRAM NEGATIVE organisms) as soon as there is a neutropenic fever
Fungal (if prolonged neutropenia and presisting fever unresponsive to anti-bacterial agents)
Protozoal e.g. PCP - more relevent to ALL
What are the cure rates of childhood ALL compared to adulthood ALL?
childhood cure rates are much higher (85-90%) than adult (about 40%)
What is the life-threatening complication of acute promyelocytic leukaemia (AML sub-type)? How is this type of AML treated?
No chemo required! Use vitamin A analogues and arsenic derivatives
What are the symptoms of lymphoma?
General symptoms (quite non-specific):
- night sweats
- weight loss
- itch without rash
- alcohol induced pain
What are the commonest causes of lymphadenopathy, in decreasing order?
Reactive (i.e. to infection)
- regional - tends to bacterial
- generalised - tends to be viral
Is lymphadenopathy in lymphoma tender?
Describe lymphadenopathy in lymphoma
no skin inflammation
Can lymphoma be diagnosed on CT?
no - need a biopsy, can only see that there is lymphadenopathy
When would you see nodular sclerosis on histology of lymph node?
CD30 protein is positive in what disease?
What is malignant haemopoiesis?
Characterised by increased numbers of dysfunctional cells with loss of the normal haemopoietic reserve.
One or more of the following:
- increased proliferation
- lack of differentiation
- lack of maturation
- lack of apoptosis
What is the main role of B cells? What is their other role?
What is the structure of antibodies?
2 heavy chains and 2 light chains
Variable regions at the antigen binding site
These structures can bind together to make different antibody types: IgA = dimer; IgM = pentamer
what is a monoclonal rise in immunoglobulin and what term is used to describe it?
All antibodies which are produced are identical because they are all coming from one clone of B cells.
What test is used to identify monoclonal immunoglobulin ?
Serum Electrophoresis - looking for paraprotein bands
Urine Electrophoresis - looking for Bence-Jones proteins
What are Bene-Jones proteins?
Light chains which are being excessively produced and excreted in the urine
How can myeloma cause renal impairment?
tubular cell damage by light chains - tubular necrosis
light chain deposition - cast nephropathy (tubes of protein which block the renal tubule making that nephron non-functional --> renal impairment. Casts seen in urine)
hypercalcaemia and dehydration
Drugs, NSAIDs (e.g. taken for bone pain)
How is cast nephropathy in myeloma treated?
Switch off light chain production with steroids/chemo
--> prevents further kidney damage if started soon enough
How can you monitor response of myeloma to treatment?
Measure paraprotein levels
What are the treatments for myeloma?
Steroids - dexamthasone or prednisolone
alkylating agents (chemo) - cyclophosphamide, melphalan
Novel agents - thalidomide, lenalidomide
monoclonal antibodies against plasma cells
High dose chemo (to make patient aplastic - get rid of own faulty cells) then autologous stem cell transplant to replace patient's cells with normal cells and regrow bone marrow (this is reserved for younger fit patients because of the risk of infection)
What should you NOT give to myeloma patients for their bony pain and why?
NSAIDs - risk of causing renal failure
What is MGUS?
patient has a paraprotein but not myeloma
benign condition which doesn't require treatment
can be a precursor for myeloma - therefore monitor paraprotein
Patients only have a small paraprotein
What would you suspect in a patient with a small paraprotein who is otherwise well, with no signs of renal impairment?
What is the structure of amyloid in the tissues?
How is AL amyloid diagnosed?
Biopsy of affected organ (or fat) and use Congo red stain - shows up amyloid as red in blood vessel walls under non-polarised light
Under polarised light shows "apple-green" birefringence
What disease produces an IgM paraprotein?
Waldenstrom's macroalbuminaemia (Lymphoplasmacystoid neoplasm)
What is the most serious complication of IgM paraprotein?
Increased plasma viscosity
(Kidney failure is not really a problem because IgM is too big to filtered out of the glomerulus and there isn't really excessive light chain production)
What are the 2 sub-types of Myeloproliferative disorder?
What are the main types within these subtypes?
- Polycythaemia rubra vera
- Essential thrombocytopenia
- Idiopathic myelofibrosis
- Chronic Myeloid Leukaemia
What supportive treatment is given to patients receiving chemotherapy?
- Prompt treatment of neutropenic fever/infection
- Broad spectrum antibiotics
- Red cell and platelet transfusions
- Growth Factors
- Prophylactic antibiotics and antifungals to prevent infections
What is neutropenic sepsis?
Sepsis + neutrophil count
How is neutropenic sepsis managed?
If patient has had chemo in the past 3 weeks and has a temp 38 or more OR clinical evidence of significant sepsis --> initiate antibiotic therapy within 1 hour - do not wait for blood results to come back. Always take blood cultures before giving abx.
- Standard risk patients (neutropenia + sepsis + SEWS 6 or more): Piperacillin/Tazobactam (gentamicin is not routine)
- High risk patients (neutropenia + severe sepsis/septic shock + SEWS 6 or more): Piperacillin/Tazobactam + Gentamicin
What are IMID drugs?
Drugs derived from thalidomide e.g. Revlimid
What chromosomal abnormality causes CML? Describe this defect.
ABL from chromosome 9 is translocated onto chromosome 22 next to BCR, forming the new chimearic gene called BCR-ABL which produces tyrosine kinase
What drug is used to treat CML?
Tyrosine Kinase inhibtors e.g. Imatinib, nilotinib, dasatinib, ponatinib
What drugs affect B cell signalling pathways in treating B cell CLL and Low grade Non-Hodgkin's lymphoma?
What do they do?
Ibrutinib and Idelalisib
Block signalling proteins in the abnormally active signalling mechanisms inside malignant cells, causing aopotosis even if there is abnormal p53 (unlike in chemotherapy, which requires functioning p53)
Give an example of a checkpoint inhibitor and what condition it can be used in
Lymphoma - esp Hodgkin's disease
What happens during immune therapy with allogenic bone marrow transplant?
T cells from the donor cause an immune attack on the cancer cells
Graft versus Leukaemia/Lymphoma effect (GvL)
But there is also immune attack of normal cells, which is very toxic - Graft versus Host disease (GvHD)
What is the likely diagnosis in patient with hillier lymphadenopathy, raised ACE enzyme levels, and malaise?
What causes lymphocytosis?
(Bordatella pertusis - bacterial infection - is the only bacterial infection which causes lymphocytosis)
neonates and infants develop a lymphocytosis in response to bacterial infection
Malignancy - CLL and lymphoma
Why might their be a mild neutropenia or thrombocytopenia associated with lymphocytosis?
Viral infection causes lymphocytosis and also mild bone marrow suppression
In a young patient, is Hodgkin's or non-hodgkin's disease more likely?
What clinical features would make Hodgkin's more likely than NHL?
Young patient, esp female
disease above the diaphragm more common in Hodgkin's
B cell symptoms: fever, itch and alcohol-induced pain more common in Hodgkin's
What are the causes of leucoerythroblastic blood picture?
Marrow stress (much more common cause): severe sepsis, severe bleeding, shock
Marrow infiltration: lymphoma, non-haemopoietic malignancies (e.g. metastasis), fibrosis
What are the causes of pancytopenia?
Increased destruction: immune, sepsis
Sequestration: hypersplenism (commonest cause of enlarged spleen is portal hypertension) - enlarged sinusoid volume so increased pooling in the spleen
Decreased production: infiltration (replacement of normal bone marrow), B12 deficiency, aplastic anaemia (immune attack on stem cells so they are removed from bone marrow), drugs (e.g. cytotoxic drugs), viruses, radiation
In what condition is Reed-Sternberg cells seen?
Describe these cells.
(but also seen in reactive lymphadenopathy esp EBV, and carbamazepine assoc lymphadenopathy)
Large, mulitnucleated, or bilobed nucleus with eosinophilic inclusion bodies --> "owl's eye" appearance
Usually CD30 and CD15 positive
Derived from B lymphocytes
A 52 year-old asymptomatic, fit man with no significant medical history has a blood count performed with the results as follows: Haemoglobin 200g/L, MCV 81 fl, white cell count 11 x 109/l, neutrophil count 7.2 x 109/l and platelet count 402 x 109/l. Blood film confirms the blood count abnormalities. What is the next appropriate investigation to do and why?
JAK2 gene analysis - a mutation in this gene is present in >95% of patients with polycythaemia rubra vera
A 21 year-old man with fatigue and easy bruising has a blood count performed with the results as follows: Haemoglobin 8.0g/L, MCV 92 fl, white cell count 50 x 109/l, neutrophil count 0.2 x 109/l and platelet count 40 x 109/l. The blood film shows an excess of blasts. What is the next most appropriate investigation and why?
Cytopenia and excess of blasts suggests an acute leukaemia - immunophenotyping will identify the lineage affected (lymphoid or myeloid), which is important for treatment as the two types are different
Which type of Hodgkin's Lymphoma has the best prognosis? Which has the worst prognosis?
Lymphocyte predominant - best
Lymphocyte replete - worst
What are the complications of tumour lysis syndrome resulting from chemotherapy?
Is lymphadenopathy more pronounced in CLL or CML?
What chronic condition is characterised by peripheral blood lymphocytosis and uncontrolled proliferation of small mature lymphocytes in bone marrow, lymph nodes (causing lymphadenopathy), and spleen (causing splenomegaly)? (monoclonal proliferation of well-differentiated lymphocytes)
What are the typical clinical features of CLL?
- weight loss