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
Mx of acute renal disease caused by myeloma
anaemia and related fatigue
bortezomib- and dexamethasone-based combination regimen for people with untreated, newly diagnosed, myeloma-induced acute renal disease.
CI -> thalidomide an dexamethasone
ANAEMIA
- erythropoiesis stimualting agents
monitoring ppl w myeloma
Ix
every 3 months for the first 5 years
– full blood count
– renal function
– bone profile
– serum immunoglobulins and serum protein electrophoresis
– serum-free light-chain assay, if appropriate.
symptoms of leukaemia
- tiredness that lasts a long time and doesn’t improve with rest (fatigue)
- bruising and bleeding more easily
- > petechia/purpura
- > blood in you rpoo
- > black, tarry poo
- > women heavy periods
- repeated infections and high temperatures (fever)
- > night sweats drenching
- unexplained weight loss
- swollen lymph nodes (glands in your neck, armpit and groin).
- enlarged spleen or liver
anaemia sx
- tiredness
- breathlessness
- dizziness or feeling faint
- chest pain
- pale skin
bone pain
what is lymphoma and its classification
cancer that starts in cells that are part of the body’s immune system lymph glands/other organs of the lymphatic system
hodgkin
non-hodgkin
what is Hodgkin lymphoma
RFs
cancer of the lymphatic system
types 1. nodular scleorsing - young - mediastinal disease 2. mixed cellularity - older - extensive disease 3. lymphocyte rich - uncommon - limited disease 4. lymphocyte depleted more common in males than females - rare - prognosis poor - any age (20-40) most common - lowered immunity - previous non-hodgkin lymphoma - EBV - FH -> First degree relatives (a parent, child, sister or brother) of people with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL) have an increased risk of getting Hodgkin lymphoma themselves. - being overweight - smoking
Sx of Hodgkin lymphoma
Ix for Hodgkin lymphoma
- painless
- enlarged
- asymmetrical
- commonly cervical LN
Constitutional Sx
- heavy sweating, especially at night
- fluctuating high temps
- weight loss >10%/6 months
- itching, which may be worse after drinking alcohol
- cough or shortness of breath
- tummy (abdominal) pain or vomiting after drinking alcohol
emergency Sx
- superior vena cava obstruction
- marrow failure
- infection
Sx if it spreads to the bone marrow
- SOB/ tiredness -> anaemia
- increased risk of infections
- bleeding problems such as nosebleeds, very heavy periods, or a rash of tiny blood spots under the skin because of a low platelet count
stages of hodgkins lymphoma
stage 1
- lymphoma in a single lymph node or one group of lymph nodes, or an organ of the lymphatic system (such as the thymus)
- lymphoma in an extranodal site (1E)
stage 2
- > 2 node sites CONFINED TO one side of the diaphragm
- your lymphoma is in an extranodal site and one or more groups of lymph nodes (2E)
stage 3
lymphoma on both sides of the diaphragm.
stage 4
- your lymphoma is in an extranodal site and lymph nodes are affected
- your lymphoma is in more than one extranodal site, for example the liver, bones or lungs
Mx of limited (early stage Hodgkin lymphoma
- excellent outcome
options
1. short course of chemo
or chemo + radio
ABVD Adriamycin=Doxorubicin Bleomycin Vinblastine Dacarbazine 2 or 3 courses BEACOPP
advanced stage Hodgkin lymphoma
- chemo +/- steroids
assessment of response to Mx
PET/CT
pulmonary function test - bleomycin
Ix for hodgkins lymphoma
normochromic normocytic anaemia
neutrophilia; eosinophilia
advanced disease - lymphopenia and loss of cell-mediated immunity Loss of lymphocytes
platelet count is normal or increased during early disease and reduced in later stages
ESR and CRP is raised -> ESR good for monitoring
serum LDH is raised initially
HIV status
Histology
Reed-Sternberg cells -> binucleate B lymph
Classification
Diagnosis of hodgkin lymphoma
multinucleate polypoid RS cell in central to the diagnosis of the four classic types
SEs of chemotherapy
nausea and vomiting diarrhoea loss of appetite mouth ulcers tiredness skin rashes hair loss infertility, which may be temporary or permanent
when do we refer someone via suspected cancer pathway for Hodgkins
presenting with unexplained lymphadenopathy. any associated symptoms
- fever
- night sweats
- shortness of breath
- pruritus
- weight loss
- alcohol-induced lymph node pain.
Diagnosis and staging of non hodgkins
excision biopsy first diagnostic procedure
CI - needle core biopsy
FISH - presenting w histologically high grade B cell lymphoma
confirm FDG-PET-CT
stage I diffuse large B-cell lymphoma by clinical and CT criteria
stage I or localised stage II follicular lymphoma if disease is thought to be encompassable within a radiotherapy field
stage I or II Burkitt lymphoma with other low-risk features.
what is non-hodgkin lymphoma
division of abnormal WBCs that are not matured so they cant even fight infections
classification
low grade - grow very slowly -> follicular is the most common
high grade -> grow more quickly -> aggressive - diffuse large B cell lymphoma is the most common
types of low grade and their features
follicular >60yrs,
- ## mantle cell lymphoma
- marginal zone lymphoma
- slow growing B cell lymphomas - small lymphocytic lymphoma - known as chronic lymphocytic leukaemia
- lymphoplasmacytic lymphoma
- skin lymphoma
RFs of non hodgkins lymphoma
Elderly
Caucasians
History of viral infection (specifically Epstein-Barr virus)
Family history
Certain chemical agents (pesticides, solvents)
History of chemotherapy or radiotherapy
Immunodeficiency (transplant, HIV, diabetes mellitus)
Autoimmune disease (SLE, Sjogren’s, coeliac disease)
H.pylor, hTLV1
Sx of non-hodgkins lymphoma
Painless lymphadenopathy (non-tender, rubbery, asymmetrical) Constitutional/B symptoms (fever, weight loss, night sweats, lethargy) Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
Ix for non hodgkins
staging
Excisional node biopsy is the diagnostic investigation of choice (certain subtypes will have a classical appearance on biopsy such as Burkitt’s lymphoma having a ‘starry sky’ appearance)
CT chest, abdomen and pelvis (to assess staging)
HIV test (often performed as this is a risk factor for non-Hodgkin’s lymphoma)
FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)
ESR (useful as a prognostic indicator)
LDH (a marker of cell turnover, useful as a prognostic indicator)
staging
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
complications of non hodgkins
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Complications related to treatment e.g. Side effects of chemotherapy
what is chronic myeloid leukaemia
ass w dysregulated production of granulocytes and the “Philadelphia Chromosome” t(9;22) a balanced reciprocal translocation
Presentation
- > 65 years
- chronic phase then transforms to an accelerated phase
- non-specific symptoms
- -> fatigue
- -> (Massive) splenomegaly
Ix
Normocytic anaemia
Neutrophilia
Absolute basophilia
Diagnosis
- Blood film and BM biopsy -> granulocytic hyperplasia with cells of all maturity
- Cytogenetic analysis (fluorescence in situ hybridisation) confirming presence of BCR-ABL1 fusion gene
Mx
chronic phase
First line = imatinib: first generation tyrosine kinase inhibitor
What is accelerated or blastic phase of CML
high balst count - 10/19%
basophil count >20%
progressive splenomegaly/WCC unresposive to tyrosine kinase therapy
first line - imatinib
second line - stem cell transplant
