Multiple Myeloma Flashcards
what group of patients does multiple myeloma commonly affect?
> 60s (peak 70s)
males>females
black Africans
what are the genes associated with multiple myeloma?
HLA Cw5
Also ATM, BRAF, CCND1, DIS3, FAM46C, KRAS, NRAS and TP53
what chromosomal factors are associated with myeloma?
chromosome 13, hyperdiploidy, and p53 deletions
what environmental factors are associated with myeloma?
agricultural, food and petrochemical industries, and long-term exposure to hair dyes
what other factors are associated with myeloma?
Monoclonal gammopathy of unknown significance
Radiation
EBV
myeloma is proliferation of which type of cell?
plasma cells
what are plasma cells?
mature B cells that secrete certain antibodies on its surface
proliferation of plasma cells leads to…
formation of abundant one type of immunoglobulin
what subtypes of immunoglobulins are common in myeloma?
IgGk
then IgA and pure light chain myeloma (k or lambda)
what is the impact of myeloma on bone marrow?
plasma cells are increased in bone marrow
pushes other immune cells out
= immunodeficiency
what is multiple myeloma
raised plasma cells in the blood and bone marrow
what is the impact of multiple myeloma on B and T cells?
B cell dysfunction – decreased humoral immunity – susceptible to bacteria
T cell function normal – viral protection
(as B cells mature in bone marrow, T cells in lymph nodes)
dysregulation of cyclin D
what is the mechanism of myeloma on bones?
Osteoclast stimulation
Osteoblast
inhibition
what is the consequence of myeloma on bones?
bone destruction
hypercalcaemia
what will ALP and bone scans show in bones of those with myeloma?
ALP normal (not high) – no stimulation of osteoblasts Nuclear bone scan not affective – no stimulation of osteoblasts = lytic
how are osteoclasts stimulated in multiple myeloma?
Bone marrow fibroblasts & macrophages produce IL-6
Myeloma cells produce IL-6
IL-6 activates RANK-ligand causing stimulation of osteoclasts
how are osteoblasts inhibited in multiple myeloma?
Myeloma cells secrete an inhibitor of osteoblast differentiation
what are the different ways kidneys are affected by myeloma?
chronic renal failure kidney stones bence hones renal disease metastases primary amyloidosis pyelonephritis proteinuria
how does chronic renal failure occur in multiple myeloma?
raised calcium, amyloid deposition, BJ proteins causing tubular obstruction, direct toxicity of paraproteins to tubules, use of NSAIDs for pain
how do kidney stones occur in multiple myeloma?
increased calcium
what is bence jones renal disease
Proteinaceous tubular casts impact on renal function (BJ, immunoglobulins, Tamm-Horsfall protein)
what is primary amyloidosis and how does it affect renal function in multiple myeloma?
AL fibrillar protein derived from immunoglobulin light chain, light chains are converted into amyloid light chain deposition in glomeruli or interstitium
why does pyelonephritis occur in multiple myeloma?
B lymphocyte dysfunction, dehydration
how does proteinuria occur in multiple myeloma?
BJ jones abundance exceeds kidneys ability to absorb protein
what is the disease progression of myeloma?
Monoclonal gammopathy of undetermined significance → smoldering multiple myeloma → multiple myeloma → plasma cell leukaemia
what are bence jones proteins?
light chains that end up in urine
what are the clinical features of bone disease in myeloma?
Pain (vertebrae, ribs, skull, sternum)
Punched out lytic bone lesions
Pathological fractures
Hypercalcaemia
what are the haematological features of myeloma?
Normocytic normochromic anaemia
Raised ESR
Increased bleeding time
what are the different neuropathies that occur in myeloma?
radiculopathy
neuropathy
how does radiculopathy occur in myeloma?
vertebrae fractures/compressions impinge nerve route
how does neuropathy occur n myeloma?
amyloid deposition infiltrates soft tissue around median nerve – carpal tunnel syndrome
what are the clinical features of hypercalcaemia in myeloma?
lethargy, confusion, weakness
what will the renal function be in those with myeloma?
reduced
what are the organisms commonly causing infection in myeloma?
S.aureus, strep pneumoniae, Klebsiella Ecoli, H influenza
what are plasmacytomas?
tumours associated with myeloma, tumours made of plasma cells
what are the symptoms of hyper viscosity syndrome?
Spontaneous gum bleeding, epistaxis, rectal bleeding, vertigo, hearing loss, paraesthesia’s, visual changes, headaches/seizures/somnolence, HF, SOB, hypoxia, fatigue
what is the general criteria of multiple myeloma?
Monoclonal protein band in serum or urine electrophoresis
Plasma cells ↑ on marrow biopsy
Evidence of end-organ damage from myeloma: Hypercalcemia, Renal insufficiency, Anaemia
Bone lesions: a skeletal survey after diagnosis detects bone disease: x-rays of the chest, all of spine; skull; pelvis +/- Tc99m MIBI and PET
what combination of major/minor criteria is required?
1 major + 1 minor, or 3 minor
what are the major criteria for multiple myeloma?
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
what are the minor criteria for multiple myeloma?
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
what is the criteria of smouldering myeloma?
o Serum paraprotein >30 g/l or urinary monoclonal protein ≥500 mg per 24 h AND/OR
o Clonal plasma cells >10% and <60% on bone marrow biopsy AND
o No evidence of end organ damage attributed to plasma cell disorder AND
o No myeloma-defining event (>60% plasma cells in bone marrow OR Involved/Uninvolved light chain ratio>100)
what is the criteria for MGUS?
o A monoclonal paraprotein band less than 30 g/l (< 3g/dl);
o Plasma cells less than 10% on bone marrow examination;
o No evidence of bone lesions, anemia, hypercalcemia, or chronic kidney disease related to the paraprotein, and
o No evidence of another B-cell proliferative disorder.
what is the criteria for stage 1 myeloma?
>35g/L albumin
<3.5mg/L a2-microglobulin
what is the criteria for stage 2 myeloma?
do not fit the criteria for the other two stages
what is the criteria for stage 3 myeloma?
<35g/dL albumin
>5.5mg/L a2-microglobulinaemia
what is the management of multiple myeloma?
VAD Stem cell transplant Combination therapy Supportive Bisphosphonates
what are the complications of myeloma?
• Renal impairment
Hypercalcaemia
Spinal cord compression Hypersensitivity
what are the complications of myeloma?
Renal impairment
Hypercalcaemia
Spinal cord compression Hypersensitivity
What is VAD chemotherapy used in myeloma?
vincristine, Adriamycin, dexamethasone,
what is the process of a stem cell transplant?
Induction therapy
Transplant - combination of steroids, cytotoxic chemotherapy (cyclophosphamide), immunomodulating agent (thalidomide or lenalidomide)
Lenalidomide/thalidomide 12 months post transplant
what is the supportive therapy used in myeloma?
Anaemia correction – blood transfusion and/or EPO
Flu vaccine and antibiotics
Pain management (beware NSAID long-term)
Orthopaedic surgery for fractures
what is the diagnostic investigations of myeloma?
detection of the light chain via serum electrophoresis + immunofixation+ FLC”
Electrophoresis
o Will show intact immunoglobulins
o Fragments of heavy or light chains
o These proteins are called paraprotein = M protein
Immunofixations – type of paraprotein
Serum FLC – increase sensitivity of the serum electrophoresis
what is the main diagnostic test for NHS in myeloma?
Bone marrow sample - shows plasma cell infiltration
What other investigations can be used for myeloma? (16)
- FBC – Hb, WCC and platelet count will be normal or low
- ESR – almost always high
- CRP – almost always raised
- Blood film – there may be rouleaux formation due to increased paraproteins
- U+E – may be evidence of renal failure – in which cases both may be high, resulting in a reduced eGFR
- Serum lactate dehydrogenase and serum β2-microglobulin – useful in predicting prognosis
- Serum calcium – normal or raised
- ALP – usually normal
- Total protein – normal or raised
- Serum albumin – normal or low
- Serum paraprotein
- Uric acid – normal or raised
- Skeletal survey –may show characteristic lytic lesions – most commonly in the skull
- Urine protein electrophoresis – identifies presence of Bence-Jones proteins
- 24-hour urine immunofixation –this is useful for checking the subtype of light chains
- Bence-Jones proteins
