Theme 7 Haematology: Myeloma, Lymphoma and Chronic Lymphocytic Leukaemia Flashcards
What is myeloma?
- an incurable malignant disorder of clonal plasma cells
- mean age of presentation = 70
- preceded by asymptomatic MGUS in all patients
Which laboratory technique is used when we suspect myeloma?
Protein electrophoresis:
- serum is placed in a gel and exposed to an electric current
- 5 fractions are usually identified
- in myeloma, there is one gamma globulin produced by malignant plasma cells producing a spike
What is immunofixation?
- performed when “M-spike” is seen on electrophosresis
- this test detects which immunoglobulin is being produced
What is meant by a spectrum of plasma cell dyscrasias?
“paraproteinaemias”
a spectrum of plasma cell disorders with MGUS having the lowest disease burden, and myeloma having the highest
What is the IMWG Diagnostic criteria for myeloma?
- clonal plasma cells > 10% AND
- CRAB features
- MDEs
What are CRAB features of myeloma?
C-Hypercalcaemia
R- Renal insufficiency
A-anaemia
B-bone lesions
What are MDEs?
- myeloma defining events
- > 60% clonal plasma cells on BM biopsy
- SFLC ratio > 100mg/L provided the absolute level of the involved LC is > 100mg/L
- > 1 focal lesion on MRI > 5mm
What is the relationship with myeloma and the kidney?
half will have persistent renal insufficiency/impairment during their disease course despite therapy
Which external factors in myeloma can contribute to renal disease?
- Renal Vein thrombosis (myeloma is a pro-thrombotic disease)
- Bisphosphonates (nephrotoxic)
- Hypercalcaemia
- ACEi
- Dehydration
- NSAIDs
- CT contrast
- Hyperviscosity
- Type 1 cryoglobunaemia
What are the clinical features of myeloma?
confusion bone pain nausea fractures constipation peripheral oedema poor appetite thirst chest infections breathlessness polyuria or oligurua/anuria
What are the acute complications of myeloma?
- hyperviscosity
- hypercalcaemia
- sepsis
- spinal cord compression
- acute kidney injury
What is rouleaux?
red cells on film stacking up like coins
How do we manage myeloma?
- steroids
- acute kidney injury with suspected myeloma is a medical emergency
time = more destruction of nephrons - blood film, electrophoresis, immunofixation, bone marrow biopsy
What do you investigate to confirm diagnosis of suspected myeloma?
Bloods:
- FBC: Hb, WB, platelets and blood film
- anaemia
- active infection
- degree of bone marrow infiltration
- rouleaux
- plasma cell present - U&Es: urea, creatinine, sodium, potassium
- Calcium
- C-reactive protein
- Immunoglobulin levels
- Protein electrophoresis looking for paraprotein
- Light chain analysis
What is MGUS?
- monoclonal gammopathy of undetermined significance
- abnormal protein (‘M’ protein) found in your blood
What is the IMWG diagnostic criteria for MGUS?
- benign disorder
- serum M-protein > 30g/L
- <10% clonal plasma cells in the bone marrow
- absence of end organ damage (CRAB)
What is the risk of progression from MGUS
1%
- most progress to myeloma
- others progress to waldenstrom’s macroglobinaemia, primary AL amyloidosis, lymphoproliferative disorders
What is the pathogenesis of AL amyloidosis?
light chain (kappa or lamda) fragments misfold and self aggregate to form beta pleated fibrils then deposit in organs
What are the clinical features of AL Amyloidosis?
macroglossia confusion poor appetite thirst palpatations breathlessness peripheral neuropathy oliguria/anuria peripheral oedema constipation ascites nausea PND and orthopnoea
What is lymphoma?
caused by malignant proliferations of lymphocytes (B or T cells)
How are B cell lymphomas classified?
according to the presence or absence of Reed Sternberg Cells
What is the name of the malignancy when Reed Sternberg cells are present?
Hodgkin Lymphoma
What are the two types of Non-hodgkin lymphoma?
(this is when Reed Sternberg cells aren’t present)
- Aggressive e.g DLBCL, Burkitt lymphoma
- rapid onset lymphadenopathy
- night sweats
- weight loss
- curable - Indolent e.g follicular lymphoma, marginal lymphoma
- insidious onset
- systemically well
- usually not curable
What are the features of Hogdkin Lymphoma?
- bimodal age distribution (20s and 60s)
- lymphadenopathy
- night sweats
- weight loss
- fatigue
- BM involvement uncommon
- excellent cure rates
What is follicular lymphoma/
- neoplastic disorder of lymphoid tissue
- type of non-hodkin lymphoma characterised by slowly enlarging lymph nodes
- M=F, incidence rises with age, median survival 8-10 years
How can we prognosticate follicular lymphoma
Using the Follicular international prognostic index (FLIPI):
- age > 60 years
- ann arbor stage III or IV
- LDH above limit of normal
- Hb < 120g/L
- presence of more than four nodal sites of disease
In the majority of cases of follicular lymphoma, what chromosomal translocation is usually present?
t (14;18) –> stops lymph nodes from apoptosing
What is the pathogenesis of Hodgkin Lymphoma?
- presence of Hodgkin Reed-Sternberg (HRS) cells within a cellular infiltrate of non-malignant inflammatory cells
- HRSS fail to express surface immunoglobulin and evade apoptosis through several mechanisms
What are the differences between acute and chronic leukaemias?
Acute:
- rapid onset
- dramatic presentation
- severe sepsis
- bleeding
- life-threateing without urgent treatment
Chronic:
- insidious onset
- doesn’t always require treatment
What are the differences between myeloid and lymphoid leukaemias?
Myeloid:
cells which develop into neuts, eosins, monos and basophils
Lymphoid:
cells which develop into lymphocytes
What is chronic lymphocytic leukaemia (CLL)
- a malignant disorder of mature B cells
- most common type of leukaemia in the UK
How do patients with CLL present?
can range from an incidental finding of lymphocytosis to widespread lymphadenopathy, splenomegaly, bone marrow failure and systemic symptoms
How do we stage CLL?
Binet system :
Stages A, B and C
looks at Hb, platelets and areas of lymphadenopathy
What is DLBCL?
- diffuse large B-cell lymphoma
- high grade lymphoma
- most common type of non-hodgkin lymphoma
What are some possible complications of CLL?
- recurrent infections secondary to reduced immunoglobulin production
- ITP
- Haemolytic anaemia
- pure red cell aplasia
- autoimmune neutropenia
