Haematology Flashcards
HL epidemiology
Men > women
Far less common than NHL
Bimodal age distribution - peaks around 20-25 and 80 years
HL risk factors
HIV
EBV
Autoimmune conditions - RA & sarcoidosis
Family history
HL clinical features
Lymphadenopathy - painless, firm, enlarged lymph nodes → most commonly found in the neck
‘B’ symptoms - unexplained fever, night sweats and unexplained weight loss
Mediastinal mass - incidental finding on imaging or present with SoB, cough, pain or SVCO
Pruritus
Hepatosplenomegaly
Malaise
Fatigue
HL ix
Diagnostic - excision biopsy of affected lymph nodes → Reed-Sternberg cells (’owl-like’ appearance)
Bloods - FBC, U&Es, LFTs, bone profile, LDH, uric acid, ESR, HIV, hep B & hep c, HTLV-1
Imaging - CXR, PET-CT, CT neck, C/A/P, MRI brain
Additional - LP and CSF analysis, echocardiogram, PFTs, bone marrow biopsy
HL staging
Lugano staging system - describes the anatomical distribution of disease & is of both prognostic and therapeutic importance
- attempt to update the Ann-Arbor system
- further modified by the presence/absence of a number of features:
- ‘B’ symptoms
- extranodal involvement
- bulky disease
HL mx
Chemotherapy and radiotherapy are the mainstay of management in patients with cHL
- ABVD regimen of treatment common - doxorubicin, bleomycin, vinblastine, dacarbazine
Relapsed disease - salvage chemotherapy, radiotherapy & autologous haematopoietic cell transplantation
Blood transfusion - must receive irradiated blood → reduce the risk of transfusion-associated graft-versus-host disease
Good prognosis — >75% of patients will be cured of condition
NHL epidemiology
- Reed-Sternberg cells are not seen in NHL
- more than 60 subtypes, a few notable ones are diffuse large B cell lymphoma, Burkitt lymphoma & MALT lymphoma
- more common than Hodgkin lymphoma
NHL clinical features
Lymphadenopathy
B symptoms - fever, night sweats & weight loss
Pruritus
Splenomegaly
Hepatomegaly
Pancytopenia
NHL ix
Bloods - FBC, ESR, LFTs, uric acid,
CXR
CT scan
Bone marrow aspirate & trephine - routine in NHL
Lymph node biopsy
Immunophenotyping
Immunoglobulin tests
HIV testing
NHL prognosis
Low-grade - generally not curable, median survival of 10 years, often widely disseminated at presentation due to them being asymptomatic
High-grade - more aggressive but more likely to be cured, deadly without treatment
NHL mx
Low-grade - depends on the subtype present, MDT discussion
- symptomless → likely no treatment will be given & will just be monitored
- radiotherapy may be curative in localised disease
- chlorambucil (chemotherapy)
High-grade - CHOP + rituximab chemotherapy regimen
- monoclonal antibodies can be useful for B cell lymphomas
ALL
- most common malignancy of childhood
- occurs due to a proliferation of malignant lymphoid progenitor cells in the bone marrow
ALL aetiology
Combination of genetic susceptibility and environmental exposure
Infection (particularly viruses) may act as a triggering event
Cytogenetic features - TEL-AML fusion gene, philadelphia chromosome (results in BCR-ABL fusion gene)
ALL clinical features
Marrow failure
- anaemia: fatigue, breathlessness, angina
- neutropenia: recurrent infections
- thrombocytopenia: petechiae, nose bleeds, bruising
Tissue infiltration - lymphadenopathy, hepatosplenomegaly, bone pain, mediastinal mass & testicular enlargement
Leucostasis - altered mental state, headache, breathlessness & visual changes
ALL ix
Bloods - FBC, LDH, uric acid, U&Es, bone profile & Mg, clotting screen, d-dimer, blood borne virus screen
Imaging - CXR (may show mediastinal mass), CT C/A/P, CT/MRI head
Bone marrow aspiration & biopsy - definitive diagnostic test → samples sent for cytogenetics & flow cytometry
Further tests - blood smear, pleural tap & LP
ALL mx
Referred a specialist haemato-oncology unit for specialist management
Key aspects: pre-phase therapy (reduce the risk of TLS), leucopheresis, supportive therapy (G-CSF may be given)
Induction chemotherapy - aim to achieve complete remission/complete molecular remission
Maintenance therapy
Stem cell transplant - allogeneic stem cell transplant may be considered & reduces the risk of relapse
Palliative care - should be considered in any patient undergoing treatment without curative intent/in those with disease symptoms that are difficult to manage
ALL complications
Tumour lysis syndrome
Neutropenic sepsis
SVCO
Chemotherapy side effects - mucositis, N&V, hair loss, cardiomyopathy, secondary malignancies
CLL
- lymphoproliferative disorder of B lymphocytes, which results from an abnormal clonal expansion of B cells
- incidence increases with age & more common in men
CLL genetic alterations
Tp53 mutation
11q and 13q14 deletions
Trisomy 12
CLL clinical features
Symptoms - weight loss, fevers, anorexia, night sweats, lethargy
Signs - lymphadenopathy, hepatomegaly, splenomegaly
CLL ix
Majority of patients with CLL are diagnosed incidentally on a FBC
Bloods - FBC, U&Es, bone profile, LFTs, blood film, haemolysis screen, immunoglobulins
Cytogenetics & immunophenotyping
Blood film - confirm the presence of lymphocytosis & characteristically shows smear or ‘smudge’ cells
Bone marrow assessment - done if concern for an alternative diagnosis
Imaging - CT C/A/P, USS, CXR
Lymph node biopsy
Virology
CLL mx
Watch and wait → used for patients with asymptomatic, indolent disease without poor prognostic factors
Chemotherapy
Small molecule inhibitors
Monoclonal antibodies
Allogenic stem cell transplantation - potential option in patients who fail chemo & BCR inhibitor therapy
Supportive care - vaccination, antibiotics for infections, IV immunoglobulin, PJP & herpes zoster prophylaxis
CLL complications
Richter transformation - formation of an aggressive lymphoma, 5-8 month median survival
Secondary infections
Autoimmune complications
Hyperviscosity syndrome
Secondary malignancies
AML
occurs due to the malignant transformation & proliferation of myeloid progenitor cells
AML risk factors
Myelodysplastic syndromes
Congenital disorders - Down’s syndrome, congenital neutropenia & Fanconi anaemia
Radiation exposure
Previous administration of chemotherapy
Toxins
AML clinical features
Presents with features of marrow failure/tissue infiltration
Marrow failure - anaemia, neutropenia, thrombocytopenia
Tissue infiltration - lymphadenopathy, hepatosplenomegaly, bone pain, gum hypertrophy, violaceous skin deposits, testicular enlargement
Leucostasis (large numbers of white cells entering the blood stream) - altered mental state, headache, breathlessness, visual changes
AML ix
Bloods - FBC, renal function, LFTs, clotting screen, d-dimer, bone profile & Mg, uric acid, LDH, blood borne virus screen
- normocytic normochromic anaemia & thrombocytopenia & reduced reticulocyte counts are common
Blood smear - Auer rods is the classical finding on peripheral blood film
Bone marrow aspirate & biopsy - allows for definitive diagnosis; samples used for cytogenetics, immunophenotyping & flow cytometry
LP - organised if there is concern of CNS involvement
AML mx
Initial management - education & support, supportive care, cytoreduction (patients with leucostasis & raised WBC), CNS involvement
Chemotherapy
AML is most common indication for allogenic stem cell transplantation
CML
Slowly progressing cancer of the myeloid cell line
CML genetics
Hallmark cytogenetic finding in CML is the Philadelphia chromosome
Results from a reciprocal translocation between chromosome 9 and chromosome 22
Abnormal chromosome 22 is characterised by the BCR-ABL1 fusion gene
CML clinical features
20-40% are asymptomatic & picked up incidentally during investigations
B symptoms
Anaemia - fatigue, breathlessness, angina
Thrombocytopenia - petechiae, nose bleeds, bruising
Splenomegaly - early satiety, abdominal pain
Bone pain
Leucostasis - headache, breathlessness, visual changes, priapism
Signs - splenomegaly, hepatomegaly, lymphadenopathy
CML ix
Bloods - FBC, U&Es, LFTs, bone profile & Mg, LDH, urate, metabolic profile, blood borne virus screen
Blood film - immature & mature myeloid cells are seen, proportion of blasts & basophils help to categorise the phase of disease
Metaphase cytogenetics - identify the abnormal chromosome 22
FISH - can be used to confirm the presence of BCR-ABL1 fusion
Bone marrow aspiration +/- trephine
CML phases
Chronic phase - clinical features are non-specific
Accelerated phase - symptoms & features become more apparent, disease more difficult to treat and outcomes worse
Blast crisis - resembles an acute leukaemia with the rapid expansion of blasts
CML mx
Tyrosine kinase inhibitors (imatinib) - blocks the enzyme created by the BCR-ABL1 fusion gene
Intensive chemotherapy - typically reserved for patients with blastic transformation
Allogenic stem cell transplantation
MM
Malignant disorder of the plasma cells
Characterised by excess secretion of a monoclonal antibody → derived from a single clone of plasma cells that have undergone abnormal proliferation
MM pathophysiology
Development of MGUS (monoclonal gammopathy of undetermined significance) - premalignant plasma cell disorder
- thought to be an abnormal plasma cell response to antigen stimulus → leads to creation of plasma cell response to antigen stimulus
Progression from MGUS to MM - further cytogenetic abnormalities and changes to the bone marrow environment occur → promotes proliferation
- associated with systemic problems due to plasma cell infiltration of the bone marrow & excess light chain secretion
MM clinical features
Constitutional symptoms - weight loss, fatigue, loss of appetite and/or generalised weakness
Bone disease - lytic lesions, can lead to fractures
Impaired renal function - light chain nephropathy
Anaemia - seen in >90%, normal bone marrow destroyed by proliferation of malignant plasma cells, EPO deficiency due to renal disease
Hypercalcaemia - MM-induced bone demineralisation
Recurrent/persistent bacterial infection
SLIM-CRAB
Emergency presentation of myeloma
Hyperviscosity syndrome - may develop with high paraprotein levels
- symptoms: blurred vision, headaches, mucosal bleeding & dyspnoea due to heart failure
- Requires urgent plasma exchange
Spinal cord compression
When to suspect myeloma
Age > 60 and:
- unexplained bone pain
- fatigue
- symptoms of hypercalcaemia
- weight loss
- symptoms of cord compression
- symptoms of hyperviscosity
- recurrent infections
MM ix
Protein electrophoresis - quantitative test that separates proteins into different bands using an electric current
- tells us whether there is an increased number of antibodies
Immunofixation - qualitative test that ‘fixes’ proteins in place by using antibodies
- tells us which type of antibody is increased
Serum free light chains - elevated ratio between light chains is suggestive of myeloma
Urine electrophoresis - light chains within the serum may be filtered by the kidneys into the urine
MM diagnostic criteria
Identification of a monoclonal antibody
Analysis of the bone marrow to look for a population of malignant clonal plasma cells
Further lab tests and imaging to assess for myeloma-related organ damage
Help differentiate between MGUS, asymptomatic myeloma & multiple myeloma
MM mx
Incurable condition, treatments aim to increase periods of disease remission
MDT discussion
Induction therapy - initial treatment option, aim to induce remission; usually combination of three drugs
ASCT (autologous stem cell transplantation) - provides best option for long period of remission
Maintenance - used to maintain disease remission as long as possible; given post-induction/post transplant
Relapse or refractory disease - almost all patients will relapse, even if they respond to treatment; therapy indicated if a clinical relapse or rapid rise in paraproteins
MM complications
Myeloma bone disease - bisphosphonates used for boney pain
Hypercalcaemia
Cord compression
Renal impairment
Anaemia
Lymphadenopathy causes
Lymphadenopathy - condition of enlarged lymph nodes
Infective - infectious mononucleosis, HIV, eczema with secondary infection, rubella, toxoplasmosis, CMV, TB, roseola infantum
Neoplastic - leukaemia, lymphoma
Others - autoimmune conditions (SLE, RA), graft vs host disease, sarcoidosis, drugs: phenytoin, allopurinol, isoniazid
Spleen functions
Immune surveillance
Proliferation and maturation of lymphocytes
Degradation of senescent & damaged erythrocytes
Hyposplenism causes
Splenectomy
Sickle-cell
Coeliac disease, dermatitis herpetiformis
Graves’ disease
SLE
Amyloid
Hyposplenism features on blood film
Howell-Jolly bodies
Siderocytes
Splenomegaly causes
Massive splenomegaly - myelofibrosis, CML, malaria, Gaucher’s syndrome
Other causes - portal hypertension, haemolytic anaemia, infective endocarditis, thalassaemia, RA
MDS
Group of malignant haematopoietic stem cell disorders
Affects elderly individuals, mean age of onset is 70 years
MDS causes
Idiopathic
Secondary to exposure - toxins, genotoxic drugs, immunosuppressive agents, chemotherapy, radiation therapy
Genetic defects
MDS complications
Pre-leukaemias, high risk of conversion to AML
Progresses slowly → most succumb to bleeding & infections before AML
MDS clinical features
Asymptomatic in early stages
Fatigue (anaemia)
Infections (neutropenia)
Bleeding (thrombocytopenia)
MDS ix
FBC - low RBCs, WBCs, platelets, normal/mildly elevated MCV, increased RDW
Low reticulocyte count, dysplastic RBCs, WBCs, normal platelets, 1-20%
Dysplastic cells, increased blasts
Chromosomal abnormalities, gene mutations
MDS mx
Medications - TNF inhibitors, DNA methylation inhibitors
Allogeneic haematopoietic stem cell transplant
- only curative option, for young individuals
- if transplant not an option → blood product transfusions, infection control (supportive)
PCV
polycythaemia = describes an increase in haematocrit, red cell count & Hb concentration
PCV reactive causes
Reactive - occurs when the Hb is elevated secondary to a low plasma volume
- can be seen in dehydration, chronic alcohol intake, excess diuretic use, pyrexia, D&V
- ‘stress polycythaemia’ - refers to reactive polycythaemia that is found predominantly in middle aged men with stressful occupations and chronically reduced plasma volumes of uncertain cause
- Gaisbock syndrome - more common in young men (smokers & associated with HTN) → reduces plasma volume, resulting in raised Hb
PCV absolute causes
Absolute - classified into primary & secondary causes
- primary - excess and uncontrolled erythrocytosis that is independent of EPO levels
- associated with mutations in JAK2 gene → uncontrolled production of blood cells, especially RBCs
- polycythaemia rubra vera = primary proliferative polycythaemia
- secondary - excess RBC is driven by excess EPO
- an appropriate rise in EPO → seen in conditions of chronic hypoxia
- anabolic steroid use
- inappropriate secretion of EPO:
- renal neoplasma
- CKS
- cyanotic heart diseases
- high-affinity haemoglobinopathies
PCV clinical features
Fatigue
Headache
Visual disturbances
Pruritus
Erythromelalgia - painful burning sensation in the fingers & toes
Arterial & venous thrombosis
Plethora
Splenomegaly
Specific clinical features of PCV:
- hyperviscosity symptoms - chest pain, myalgia, weakness, headache, blurred vision & loss of concentration
- ruddy complexion
- splenomegaly
PCV ix
Bedside - pulse oximetry to look for possible secondary polycythaemia
FBC - raised haematocrit, raised Hb, raised red cell mass with low/low-normal plasma volume, raised leukocytes & platelet counts
- neutrophil count & platelet count are usually normal in secondary polycythaemia !
Renal function & urate
Vitamin B12
EPO levels
JAK-2 mutation
Bone marrow biopsy - hypercellular bone marrow
Important to exclude CML - cytogenetics
PCV mx
Possible underlying causes should be corrected
Venesection
PV:
Regular venesection
Aspirin 75mg daily
Cytoreductive therapy to suppress erythropoiesis in those where venesection isn’t sufficient/those at high risk of thrombosis
- 1) hydroxycarbamide - suppresses erythrocytosis & causes a macrocytosis
- 2) interferon, JAK2 inhibitors (first line in younger patients)
- 3) bulsulfan
Other interventions - allopurinol (hyperuricaemia), antihistamines, SSRIs or interferon (for pruritus)
ET
myeloproliferative disorder caused by dysregulated megakaryocyte (platelet precursor) proliferation
ET epidemiology
Women aged 50-70 years
Median survival is 10-15 years
ET clinical features
50% of patients are asymptomatic with only an incidental FBC finding
Thrombosis (arterial or venous)
Bleeding
Hyperviscosity-related → dizziness/syncope, headache
Splenomegaly
Hyposplenism
Erythromelalgia (red/blue discolouration of the extremities, often accompanied by a burning pain)
Livedo reticularis (net-like purple rash)
ET ix
FBC - persistent platelet count significantly >450 x 10^9/L
Genetic testing - JAK2 mutation
Trephine biopsy - hypercellular marrow & pathological megakaryocytic clumping
ET mx
Based following risk stratification
Low risk - treat with aspirin alone
Intermediate risk - treat with either hydroxycarbamide & aspirin OR aspirin alone
High risk - hydroxycarbamide & aspirin
Can also used hydroxyurea & anagrelide (specialist platelet-lowering agent)
Myelofibrosis
chronic myeloproliferative neoplasm characterised by the gradual replacement of normal bone marrow tissue with fibrous tissue
Myelofibrosis aetiology
Associated with genetic mutations
- JAK2
- CALR
- MPL
Myelofibrosis clinical features
Constitutional symptoms - weight loss, fever, night sweats
Marrow failure - anaemia, recurrent infection & abnormal bleeding/bruising
Bone pain
Haemorrhage & thrombosis (less common compared to other myeloproliferative disorders)
Splenomegaly - abdominal discomfort, early satiety
Hepatomegaly
Myelofibrosis ix
Blood film - poikilocytes (tear-shaped RBCs) & a leucoerythroblastic blood film
Platelet count & WCC are often high initially, with pancytopenia occurring later
Difficult to aspirate the bone marrow → resulting in a ‘dry tap’
Trephine biopsy shows evidence of fibrosis, with hypercellular tissue, reduced fat space & increased reticulin staining
Urate and LDH usually high
JAK2 is positive in 50% of cases
Myelofibrosis mx
Generally an incurable condition
Allogeneic stem cell transplantation is the one exception → patients aged <70 years with good performance status & high-risk disease
JAK-2 inhibitors (ruxolitinib) can have a good effect particularly in reducing splenomegaly & treating B symptoms
Cytotoxic agents, immunomodulatory drugs, splenic irradiation & splenectomy can be used as treatments to lessen the need for transfusion & improve symptom control
Myelofibrosis complications
Transformation to acute leukaemia
Splenomegaly-related complications
Cardiovascular and thrombotic events
