haematological malignancies Flashcards
what is leukaemia and classification
affects the bone marrow with ir wihtout released circulating neoplastic cells in the blood
an increase in the number of WBCs
- Acute lymphoblastic leukaemia (ALL)
- Acute myeloid leukaemia (AML)
- Acute promyelocytic leukaemia (APL)
- Chronic lymphocytic leukaemia (CLL)
- Chronic myeloid leukaemia (CML)
- Childhood leukaemia
what is acute lymphobalstic leukaemia - ALL
RFs
Sx
- Proliferation of lymphoid blasts (B or T cell)
- Patients can present with symptoms of pancytopenia. Bone pain also a common symptom
- Multi-drug chemotherapy
RFs
- age - younger than adults
- sex - M>F
- certain genetic conditions
- exposure to very high doses of radiation
Types
B or T cell
philadelphia positive ALL -> not inherited
Sx
- extreme tiredness
- unexplained bruising or bleeding
- weight loss
- infections that last longer or recurrent
- swollen glands
Ix FBC, LFTs, U&Es, infection screening BM biopsy - Diagnositc Cytogenetics - Mx Flow cytometry -> pattern fo proteins on the surface of leukaemia
what is acute myeloid leukaemia
Mx
Ix
- Patients can present with pancytopenia
RFs
- age esp >60
- sex M>F
- FH
- radiation and chemical exposure
- myelofibrosis
- myelodysplastic syndromes
- previous Mx using chemo/radio
features - tiredness - bruising - bleeding - swollen lymph glands - Auer rods leukoerythroblast - Classification based mainly on cytogenetic abnormalities and morphology
Treatment
- Intensive vs non-intensive
- Standard of care = trial
- Allogeneic stem cell transplant if poor risk
- Palliative/supportive care for some patients
Morphology Flow cytometry Immunohistochemistry Cytogenetics Mutationals
what is chronic lymphocytic leukaemia
increased number of mature lymphocytes >5 x 10^9/l
RFs
- age -> >70
- M>F
- monoclonal B-cell lymphocytosis
- exposure to radiation
Sx
- mostly during routine blood tests or a check up
- tiredness
- swollen lyph glands
- night sweats
- infection
Mx
- asymptomatic - watchful waiting
- symptomatic/blood levels low then CHEMO
B-CLL is the most common
flow cytometry used to confirm the diagnosis
epidemiology and aetiology of myeloma
- affects 4 per 1000
- age - above 65
- higher amongst african-americans
- more common in men than women. (CANCER.ORG)
- obesity
- MGUS
- FH of myeloma increases risk by 2/3 x
- HIV/organ transplanted ppl
- Median age at onset is 71yrs but 10-15% are under 45yrs
- Median survival 3 yrs; 10% survival at 10yrs
Characterised by significant immune dysfunction
pathology of myeloma
b cell cancer caused by a clo nal proliferation of mature plasma cells that secrete immunoglobulins or fragments
undergo immunoglobulin class switching and somtic hypermutation -> overproduction of a single immunoglobulin class -> paraprotein
once mutated they typically migrate to the bone marrow -> BM infiltration
dysregulation of the osteoprotegrin rankl system by tumour secreted cytokines -> osteolysis and produce destructive bone lesions
unregulated pro- liferation of monoclonal plasma cells in the bone marrow.
their accumula- tion leads to anaemia and eventually marrow failure, and indirectly to bone resorption resulting in lytic lesions, generalized osteoporosis, and pathological fractures.
CFs of myeloma
CRABBI
- Calcium
- Hypercalcaemia occurs as a result of increased osteoclast activity within the bones
- This leads to constipation, nausea, anorexia and confusion - Renal
- Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
- This causes renal damage which presents as dehydration and increasing thirst
- Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis - Anaemia
- Bone marrow crowding suppresses erythropoiesis leading to anaemia
- This causes fatigue and pallor - Bleeding
- bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising - Bones
- Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
- This may present as pain (especially in the back) and increases the risk of fragility fractures - Infection
- a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
incidental finsing with pancytopenia or anaemia
Red flags - unexplained back pain, night sweats, weight loss and extreme lethargy
complications -> renal impairment, progressive renal failure -> amyloidosis or deposition of paraprotein in the kidney
Ix of myeloma
- FBC
- normocytic/normochromic anaemia of chronic disease -> anaemia/pancytopenia -> BM infiltration
thrombocytopenia - ESR
- raised - U&Es - raised calcium and urea and creatinine
- blood film - formation of rouleaux - this is due to increased proteins also increases ESR
suspect cancer NICE
- Use serum protein electrophoresis and serum-free light-chain assay
serum immunoglobulins to confirm the presence of a paraprotein indicating possible myeloma
urine - bence jones proteins
Diagnostic Ix for NICE
BM aspirate and trephine - more than 20% plasma cells seen - morphology
flow cytometry - determine plasma cell phenotype
- strongly positive for CD138 (identify the adverse risk abnormality via FISH) and cytoplasmic immunoglobulin
- negative for CD5, CD20, surface
CD138 positive and the total plasma % shows the extent of plasma infiltration
normal plasma cells express CD19 but malignant cells DONT
imaging for suspected myeloma
whole body MRI as FIRST LINE
unsuitable/declines whole body CT
unsuitable/declines
skeletal survey
xray - rain drop skull
Mx of myeloma
assess the suitability of people with myeloma for first autologous stem cell transplant -> assess using frailty and performance status measures
what do u take into when thinking about allongenic stem cell transplantation
- whether the person has chemosensitive disease
- how many previous lines of treatment they have had
- whether a fully HLA matched donor is available
- how GvHD graft-versus-host disease and other complications may get worse with age
- the risk of higher transplant-related mortality and morbidity, versus the potential for long-term disease-free survival
- improving outcomes with other newer treatments
- the person’s understanding of the procedure, and its risks and benefits.
transplant suitable
first line Mx
second line Mx
induction therapy
- bortezomib + dexamethasone + thalidomide
newly diagnosed multiple myeloma
maintenance Mx - lenalidomide
treosulfan conditioning Mx before allogenic
SECOND line Mx
transplant unsuitable 1st line
2nd line
thalidomide + alkylating agent + corticosteroid
thalidomide CI -> bortezomib
2nd LINE
carfilzomib w dex
symptomatic muliple myeloma define with what
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within the serum or the urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
preventative measures taken for complications of myeloma
bone disease
- zoledronic acid -> disodium pamidronate
- before starting - dental assessment
infection
- seasonal Flu vaccine
- pneumococcal vaccine under 65
- hypogammaglobulinaemia and recurrent infections.-> IV Ig
- aciclvoir if they were on steroids, bortezomib
