cancers of the blood Flashcards
what is multiple myeloma?
malignant disorder of plasma cells - b cells
what occurs within MM?
excessive secretion of monoclonal AB
what is the path of MM and the monoclonal AB?
excessive AB secretion
1. development of monoclonal gammopathy of undetermined significance MGUS
2. progression to MM
what is MGUS?
where most cases of MM arise from?
1. inciting event: initial cytogenic event abnormality - abnormal plasma cells clone secreting AB
2. progression to MGUS to MM: more cytogenic changes including change to bone marrow - bone cell infiltration
what are the clinical features of MM?
C: calcium - high
R: renal impairment
A: anaemia
B: bone disease
at what point is hypercalcaemia a medical emergency?
greater than or higher to 2.9mmol/L
why is anaemia seen in MM?
EPO deficiency
how is bone disease seen on imaging?
lytic lesions
what are the red flag symptoms seen in MM?
weight loss
anorexia
generalised weakness and excessive fatigue
apart from CRAB, what other features are seen in MM?
paraesthesia, splenomegaly, hepatomegaly, lymphadenopathy, neuro conditions: hyperviscosity conditions, spinal cord compression
what is hyperviscoisty syndrome?
headache, blurred vision, SoB, mucosal bleeding
how do you screen for MM?
investigate for monoclonal AB- protein electrophoresis and immunofixation
what immunoglobulins are assessed for?
igM - electrophoresis
immunofixation - higher ratio of heavier chains
how do you manage bony pain in MM?
bisphosphonates
what is ALL classically associated with?
most common in paeds
down syndrome
what is CLL most associated with?
warm haemolytic anaemia, Richter’s transformation and smudge cells
what is ritcher transformation?
CLL can transform into into aggressive lymphoma
what is CML linked to?
three phases - long chronic phase
philadelphia chromosome
what is AML linked to?
transformation from myeloproliferative
auer rods
what is burkitts lymphoma?
high grade B cell neoplasm
what are the two major forms of burkitts lymphoma?
endemic - african - maxilla/ mandible
sporadic- ileo caecal - usually HIV pts
what is burkitts associated with?
c-myc gene translocation t(8:14)
EBV linked to african form
what would microscopy show in burkitts?
starry sky
lymphocyte sheet interspaced with macrophages containing dead apoptic tumour cells
how is burkitts managed?
chemo - which can cause tumour lysis syndrome
what would indicate tumour lysis syndrome?
high k+
high phosphate
low ca2+
acute renal failure
hyperuricaema
what can help prevent tumour lysis syndrome in chemo for burkitts?
rasburicase
what is hodgkins lymphoma?
malignant proliferation of lymphocytes
what is seen on microscopy for hodgkins?
reed-sternberg cells
what age is hodgkins lymphoma most common
20s and 60s
what are RF for hodgkins lymphoma?
EBV
HIV
how does hodgkins lymphoma present?
lymphadenopathy - cervical/ supraclavicular - then axilla then inguinal
painless, non tender
B symptoms
mediastinal mass - cough, weird CXR
what is seen with alcohol and hodgkins lymphoma?
alcohol induced pain
what are B symptoms ?
weight loss
fever
night sweats
pruritic
what investigations are done for hodgkins lymphoma and what is seen?
FBC - normocytic anaemia
hypersplenism
coombs +ve
eosinophilia
high LDH
lymph node biopsy - reed sternberg cells
why is there eosinphillia in hodgkins?
more cytokines eg IL- 5
which hodgkins prognosis is worse?
lymphocyte depleted
B symptoms - usually poor prognosis
which hodgkins prognosis is best?
lymphocyte predominant
what are the different chemo combos in hodgkins lymphoma?
ABVD: standard
BEACOPP: more toxic but more likely to go into remission
what are the management options of hodgkin lymphoma?
chemo
radiotherapy
combined chemo then RT
haemotopoietic cell transplantation - relapsed/ refractory hodgkins
what is differenced between non hodgkins and hodgkins?
hodgkins - reed sternberg
non- hodgkins - everything else
what is non-hodgkins lymphoma?
malignant proliferation of lymphocytes in lymph nodes or other organs
can affect B/T cells
what is the 6th most common cancer in the UK?
non-hodgkins
who is affected more in non-hodgkins?
men more then females
what are RF for non-hodgkins?
elderly
cauasians
EBV
FamHx
chemical exposure - pesticides, solvents
previous chemo/ RT
immunodeficiency - transplant, HIV, DM
autoimmune conditions - sjogrens, SLE, coeliac
how does non-hodgkins present?
non tender painless lymphadenopathy - rubbery, asymmetrical
B symptoms
other systems - gastric - abdo pain, dsyphagia,
bone marrow - bone pain, pancytopenia
testicular masses
fever
what investigations are needed within non-hodgkins?
excisional biopsy
CT TAP
ESR - prognostic indicator
HIV test
LDH
FBC - normocytic anaemia
PET CT
what is LDH?
lactate dehydrogenase
cell turnover - prognostic indicator
how is non-hodgkns managed?
specific to sub type
rituximab in combo
neutropenia - prophylactic ABx
flu/ pneumococcal vax
whoch grades have best prognosis in non-hodgkins?
low grade - better prog
high grade - worse prog but better cure rate
what are complications of non-hodgkins?
bone marrow infilitration
spinal cord compression
Superior vena cava obstruction
side effects of chemo
mets
what is ALL?
acute lymphoid leukaemia
neoplastic malignant proliferation of lymphoblasts - immature lymphoblasts accumulate in bone marrow
usually B cell
what are RF for ALL?
young age
B cell - peaks at 3yrs
T cells - peak at 15-20
down syndrome
radiation exposure
what are signs of ALL?
abrupt onset
anaemia - fatigue, SoB, pallor
neutropenia - fever, sepsis, pneumonia
bone pain
hepatosplenomegaly
lymphadenopathy
how is ALL diagnosed?
FBC/ blood film: more lymphoblasts
high WCC
BM film: lymphoblast dominance - starry sky, mitotic figures
immunophenopathy- +ve nuclear staining
how is ALL distinguised from ALL on the investigations?
ALL - immunophenotyping is +ve
AML: -ve
how is ALL managed?
aggressive chemo
- more successful in kids
if brain mets: intrathecal chemo/ RT
tyrosine inhib: imatinib, dasatinib
what is the ALL/ AML ABCDEF ?
A - acute
B- blast prodinate
C: children
D: drastic course
E; elderly
F: fair few WBC and fever
what is AML?
neoplastic monoclonal prolif of myeloblasts in BM - accumulate of myeloblast
what are RF of AML?
adults - peaks at 60yrs
radiation/ chemo
down syndrome - <5yrs
myeloproliferative disorders
what are complications of AML?
DIC
what are signs of AML?
abrupt onset
anaemia
thrombocytopenia
neutropenia
leukaemia cutis
gum swelling
what is leukaemia cutis ?
skin infiltration of aml
how is AML diagnosed?
FBC/ blood film - high leucocytes, anaemia
BM smear: high myeblasts. auer rods
how is aml managed?
chemo
promyelotic - all trans retonic acid treatment
BM transplant
what is CLL?
chronic lymphoid leukaemia
neoplastic monoclonal proliferation og fucntionally abnormal B cells
what can cause CLL?
chromosome abnormalities
mutations in tyrosine kinase pathways
what are RF of CLL?
fam history
agent orange exposure
what are symptoms of CLL?
late onset
anaemia
thrombocytopenia
neutropenia
neoplastic infilitration
what are complications of CLL?
abnormal iG secretion - hypogammaglobulinemia, autoimmunity
ritcher syndrome - progress to aggressive lymphoma
how is CLL diagnosed?
FBC/ blood film - lymphocytosis, smudge cells
immunophenotyping - CD5, CD20, CD23
lymph node biopsy - small round lymphocyte infilitration
what are smudge cells ?
disruption of fragile membranes of abnormal lymphocytes
how is CLL managed?
chemo/ RT
BM transplant
immunotherapy
what is CML?
chronic myeloid leukaemia
monoclonal proliferation of mature granulocytes/ precurosrs
what are granulocytes?
eosinophils
basophils
neutrophils
what Chr is linked to CML?
philadeplphia
cheese - C
milk - M
what are RF for CML?
adult - above 40
radiation exposure
benzene exposure
what are the three phases of CML?
chronic
accelerated
blast crisis
what occurs within chronic phase of CML?
mainly neutophil dominance
B symptoms
what occurs within accelerated phase of CML?
more basophils
anaemia
hepatosplenomegaly
lymphadenopathy
recurrent infections
bleeding
petechiae
ecchymose
what is ecchymose?
bruises
what occurs within blast crisis of CML?
rapid progression - poor prog
more myeblasts
bone pain
fever
significant splenomegaly
how is CML diagnosed?
more granulocytes
BMM biopsy: hypercellularity of myeloid
how do you manage CML?
tyrosine kinase inhib: imatinib, dasatinib nilotinib
BM transplant
