Haematological Malignancies - Multiple Myeloma Flashcards
what is it malignant disease of?
plasma cells
change in the plasma DNA
what is myeloma
collection of different types of the same cancer
what is plasma
type of WBC in the BM which remains in the BM for many years
what is the role of the plasma
immunity, fighting infections, disease
remembers previous germs which invaded the body
how does myeloma develop
plasma genetic material is damaged and not repaired, the damaged genes control the cell cycle
plasma cells then divide more quickly
all new cells have the same genetic change as the inital cell, which gives rise to a population of identical or monoclones.
over time one or more gets more damages which develop and multiply, these are different subclones or populations of abnormal plama cells
what happens to the subclones
they compete for resources in the BM, some depend on others for survival, in the right environment they survive and thrive so the myeloma progresses
treatment destroys some subclones, some may have resistance. remaining subclones act dormant for a period of time, giving a period of remission however will become active again of they incur further damage or if they are in a favourable environment [why relapse occurs]
selection of clones
with successive lines of trt the toughest clones are naturally selected for survival, these are resistant to treatment
what will help with choosing what trt to give
understanding the pt myeloma and how it evolves
what works at a balance
oestoclastic and oestoblastic activity
describe what happens to bone due to myeloma
malignant cells secrete cytokine [oestoclastic activating factor]
increase in osteoclatic activity compared to osteoblastic
bone breakdown at a faster rate
build up in the BM means there isnt enough space for normal cells
what are the risks for MM
family history
more common in african americans
lowered immunity = organ transplant, HIV
small increase in obesity
small increase due to prior radiation
increases with secondary event, in order to trigger leukaemia in order for it to evolve
age [rare under 40]
how is MM diagnosed
end of organ damage (hypercalcemia, renal impairment, anaemia, bone lesions)
presence of M protein (in blood or urine)
plasma cell number (bone marrow and/or lesion)
stage 1
albumin + b2m = near normal
stage 2
albumin = low
b2m = normal or slightly raised
stage 3
albumin = low
b2m = very high
what is albumin
protein which helps blood remain in the arteries/ veins and carry hormones
normal range = 3.4-5.4g/dl
what does low levels of albumin indicate
kidney and liver problems
what does high levels of albumin indicate
dehydration, raised with steroids
what is b2m
beta-2-macroglobulin
found on MHCL which can shed into the blood - tumour marker
normal range: 0.7-1.8 mg/ml
what are the symptoms
bone pain (70%)
fractured bones
recurrent infections/ unable to shake them off
spinal cord comp
bruising (rare)
high Ca in blood = bone damage
constant thirst
frequency
confusion or drowsiness
if untreated death
what are the kidney issues
abnormal plasma produce high levels of immunoglobin
bence-jones protein (antibody)
nausea
loss of appetite
dehydration
fatigue, lack of energy
swollen feet, ankles, hands
what are the investigations
blood test: M protein levels
bence-jones urine test
FBC: pancytopenia + hypercalcemia
urea and creatinine - kidney function
plasma viscosity
skeletal survey: PET/ MRI spine
BM biopsy
full body MRI/CT - bony deposits
stage 1
x-rays are normal, solitary plasmacytoma
Hb > 10.5 gm/dl
blood Ca is 12mg/dl or greater
M proteins and IgG <5g/dl
IgA is <3g/dl
light chains in urine <4g in 24 hours
stage 2
more advanced than stage 1 but less advanced than stage 3
2A = no kidney failure
2B = kidney failure present
stage 3
x-ray show more than three bony lesiosn
Hb < 8.5 gm/dl
blood Ca is >12mg/dl
M proteins and IgG >7g/dl
IgA is >5g/dl
light chains in urine >12g in 24 hours
is there a curative option
NO
what is the RT
spinal cord comp
pain relief
post-op: pain and local control
avoid pathological fracture
what are the palliative options
RT
surgery
watch and wait: if disease isn’t causing issues
biphosphonates
chemo/immunotherapy
why is biphosphonates given
for bone loss
inhibits effects of oestoclasts
if taken for a long time then it has SE
what is the chemo/immuno given
often in combination
targeted drugs: thalidomide, lenalidomide, bortezomib, daratumumab
chemo: cyclophosphamide, melphalan
steroids: prednisalone, demethasone
what is a solitary bone plasmacytoma
single mass of plasma cells in either bone or soft tissue [soft tissue = extramedullary] which has a bubble like appearance
why does careful monitoring of a solitary bone plasmacytoma needed
as it can develop into myeloma
RT for a solitary bone plasmacytoma
curative intent
tech depends on location
often 40-50Gy in 20-25 however location dependent
pain control and symptom control [cord comp]
avoid a pathological fracture
post op = pain and local control
shouldnt compromise QoL
is plasmacytoma the same or different to myeloma
DIFFERENT
how do lymphoma and MM differ
MM latches onto bone and don’t end up in the lymphatics
