Multiple myeloma Flashcards
Who gets myeloma
Elderly - median age presentation is 70
What is multiple myeloa
Plasma cell proliferation haem malignancy from mutation as B lymphocytes -> mature plasma cells
Clinical features of MM
CRABBI
Calcium high
Renal impairment
Anaemia
Bleeding - TP
Bones Pain + fractures
Infection
What causes hypercalcemia in myeloma
Increased osteoclast bone resorption due to cytokines from myeloma cells
Renaldysfuctnion
Hypercalcemia features
Constipation, nausea, anorexia, confusion
Renal problems in myeloma cause
Monoclonal productuon IgGs -> light chain deposition in renal tubules
Renal damage -> dehydration and thirst
also amyloidosis, nephrocalcinosis, nephrolithiasis
What causes bone pain and pathological fractures in myeloma
Bone marrow infiltration by plasma cells and cytokine mediated osteoclast activity -> lytci bone lesions
Other features of myeloma not pneumonic
Amyloidosis eg macroglossia
Carpal tunnel
neuropathy
Hyperviscosity
How assess for myeloma in over 60s
FBC, calcium, plasma viscosity or ESR
When assess for myeloma
General screen - >60, persistent bone pain esp back pain or unexplained fracture
When urgent electrophoresis for myeloma
> 60
Hypercalcemia or leukopenia
Presentation suggests myeloma
OR
pllasma viscosity or ESR and presentation consistent
How investigate for myeloma initially
FBC, calcium (bone profile), plasma viscoity, ESR
Consider - blood silm, U+Es
Urgent plasma electrophoresis and bence jones protein urine test within 48 hrs
When refer for myeloma
When electrophoresis/bence jones test +
Blood film in myeloma
Rouleaux formation
What see on electrophoresis in myeloma
IgA/IgA proteins in serum, bence jones in urine
Further investigations myleoma
Bone marrow aspiration - plasma cells raised
Skeletal survey
Whole body MRI
X rays -> rain drop skull
What see on X ray in myeloma
Rain drop skull - splashing = dark spots random
V SIMILAR TO PEPPER POT SKULL IN PRIMARY HYPERPARATHYROIDISM
Look at x rays to differntiate
Diagnostic criteria for myeloma
1 - clonal bone marrow plasma cells >10% OR biopsy proven plasmacytoma
2 - one or more myeloma defining events:
->60% plasma cells in marrow
-Light chain ration >100
2 > focal lesions on MRI >5mm
-Hypercalcemia >2.75mmol/l or o.25 over normal
-Renal insuff - >177 umol/l creatinine or clearance <40ml/min
-Anaemia <100g/l or 20 below normal
-1 or more lytic bone lesion on X ray, CT or PET/CT >5mm
Why is allogeneic stem cell transplant not used in myeloma
Hgh overall mortatlity and GvHD
What is autologous HSCT
Removal of paitents own stem cells prior to chemo, replaced afterwards
Porlongs event free and overall survival
Induction regime myeloma
Targeted drugs eg thalidomide, lenalidomide, bortezomib daratumumab
Chemo eg cyclophosphamide or melphalan
Steroids eg pred or dex
Complications fo myeloma
Pain
Pathological fracture
Infection
VTE
Fatigeu
Supportive managmenet myeloma
Analgesia
Zoledronic acid = manage osteoporosis
Infection - flu vaccine, IgG repllacemetn
VTE prophylaxis
Fatigue - consider EPO
What is staging of myeloma based on
B2 microglobulin
Albuin levels
Stage I -III myeloma
I - B2 microglobulon <3.5mg/l
Albumin >35g/L
II - not either
III - B2 microglobulin >5.5mg/l
Poor prognosis cytogenetic abnormalities for myeloma
t4:14, 14:16, 14:20
del 17p and gain 1q
How measure performance status
Eastern Cooperative Oncology Group (ECOG) scale or the Karnofsky Performance Scale (KPS)
Poor prognostic factors
Specific cytogenetics
Performance status
Age and comborbities
Response to treatmnet initially (Complete, v good partial = better)
Albumin
Peripheral blood plasma cells (abnormal to see out of marrow)
LDH level
Serum B2 micoglobulin (high = bad)
Eligible for autologous stem cell transplantation
Minimal residual disease
What assess after treatment for myeloma
MRD assess for residual myeloma cells after treatment
Negativity ass w prolonged progression free survival and overall survival
Prognostic models myeloma
Revised international staging system - ISS stafe, risk cytogenetics, LDH level - I-III
Myeloma risk stratification -
Risks for myeloma
Radiation, agriculture, metals, rubber, chemicals and combustion fuel prodyucts
FH, genetics implicated
Dont know cause
What is myelomas premalignant phase
Monoclonal gammopathy of uncertain significance
Myeloma cells on blood film
Perinuclear halo
Large cells
Eccentric nucelus
Large amounts ble cytoplasms
What is myeloma characterised by
Monoclonal protein in serum/urine
Lytic bone lesions
Excess plasma cell sin bone marrow
What is electrophoresis testing for
The ‘antibodies’ OR only light chain proteins released by myelomas (cancerous plasma B cells) causing the symptoms
What are lytic lesions
Destruction of bone tissue around myeloma tumours
What does M protein cause
Neuropathy and renal compromise
Renal damage mechainsm myeloma
Light cahins filtered into glomerulus- not all light chains reabsorbed -> loop of henle -> jelly/cast formation in loop of henle destroying a nephron -> casts
Preventing renal damage in myeloma
Early diagnosis
High fluid intake at least 3 litres/day
Bring down calcium
Potentially nephrotoxic drugs eg aminoglycosides, NSAIDs avoided, monitor bisphosphonates closely
Treat infection
Complication of pathological fractures in back
sPINAL CORD compression
Bone disease in myeloma pathology
Increased osteoclast bone resorption due to cytokines from myeloma cells -> increased bone resorption, hypercalcemia, decreased osteoblastic activity and impaored glomerual filtration
Bone disease and hypercalcemia emergency treatment
IV fluids, steroids, bisphosphonates
Benefits of bisphosphonates in myeloma
Prevent vertebral fractures amerlioration of pain
Prolong PFS, OS
reduction in m non vertebral fractures and hypercalcemia
Can you cure multiple myeloma
No
What infections are myeloma patients particuarly at risk of
Strep pneumoniae
H.influenzae
VZV recurrence shingles
