haematology Flashcards
what is multiple myeloma?
Cancer of differentiated B-lymphocytes, known as plasma cells
- production of a characteristic paraprotein
what is CRAB acronym, relating to myeloma?
-manifestations of multiple myeloma
C - Calcium elevation - Ca>0.25mmol/l above upper limit of normal or >2.75mmol/l
R - Renal impairment - creatinine>173mmol/l
A - anaemia - 2g <NR or <10g/dl
B - Bone abnormalities - lytic lesions, osteoporosis c compression, spinal cord compression
what do myeloma cells produced that can be detected?
- intact immunoglobulin product (paraproteins) - IgG (2/3), IgA (1/3) or rarely IgD (1.8%), IgM (0.4%) or IgE
- monoclonal free light chains
what is MGUS?
monoclonal gammopathy of undetermined significance
- non-cancerous, paraprotein made
- associated with increased risk of developing multiple myeloma
- not treated unless develops to multiple myeloma
what is smoulldering myeloma?
- abnormal cells detected but no symptoms
- can progress to symptomatic myeloma but at a slow rate
- not treated until it progresses
what is the treatment for multiple myeloma?
- combined chemotheraphy
- stem cell transplantation
- additional treatment - Bisphosphonates (for bones), renal dialysis, spinal cord compression treatment (radiotherapy, surgery), pain relief - to reduce symptoms and damage
what are the 2 types of stem cell transplants?
- autologous - from patient, no rejection, for myeloma/lymphoma
- allogeneic - from donor, rejection possibility, for blood cancers like AML, ALL, MDS
what is the classification of lymphoma?
HODGKIN LYMPHOMA or NON-HODGKIN LYMPHOMA
(if non-hodgkin lymphoma) - aggressive or idolent
in non-hodgkin lymphoma, what cells are effected?
B-cells - 90%
T-cells - 10%
NK-cells 1%
what are the sub-types of idolent lymphoma?
- Follicular Lymphoma
- Marginal Zone Lymphoma
- Mantle Cell Lymphoma
- CLL
(all Slow growing and advanced at presentation)
what are the risk factors for idolent lymphoma?
- Primary Immunodeficiency e.g. Wiscott-Aldrich Syndrome
- Secondary Immunodeficiency e.g. HIV
- Infection e.g. EBV; HTLV-1; Helicobacter Pylori
- Autoimmune Disorders
what are human leukyocte antigens?
- complex of genes on chromosome 6 in humans which encode cell-surface proteins
- used to match donors in stem cell transplants
- 6 main HLA loci –A, B, C, DP, DQ, DR
what are the clinical presentations of idolent lymphoma?
- painless lymphadenopathy - lymph nodes swelling
- Association with B-Symptoms – Fevers, Night Sweats and Weight Loss
- infections
- Compression Syndromes
- Organ Involvement - splenomegaly, hepatomegaly
what are the investigations done for idolent lymphoma?
- Lymph Node Biopsy – Core Needle Biopsy / Excision Node Biopsy
- possible bone marrow biopsy
- imaging - to determine staging classification
- bloods
- WHO performance status
what are the different treatment options for various lymphoma?
- active surveillance
- radiotherapy - local control
- Chemoimmunotherapy - Monoclonal Antibodies/Maintenance therapy
- Small molecules inhibitors / Novel therapies
- Bi-Specific T-Cell engaging Antibodies and (CAR) Chimeric Antigen Receptor T Cells
what are some Small molecules inhibitors / Novel therapies
for idolent lymphoma?
- Brutons Tyrosine Kinase Inhibitors
- BCL2 Inhibitors
- IMiDs
what is Graft-versus-Host Disease?
disorder that occurs when the graft’s immune cells recognize the host as foreign and attack the recipient’s body cells
- “Graft” refers to transplanted, or donated tissue
- mild to life threatning
what is the difference between acute vs chronic GvHD?
acute - skin, liver, GI tract, occurs within 100 days of stem cell transplant
chronic - any tissue, no time limit
what is conditioning therapy in haemopetic stem cell transplantation?
- eg chemotherapy to eradicate disease and for immunosuppression
what is the first-line treatment for acute GvHD?
corticosteroids
what are clinical signs of GvHD?
mouth lesions/ulcers
rash
depends what organs effected eg diahrroea if GI
what is Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (vod/sos)
- complication after hematopoteic stem cell transplantation
- damage to the small blood vessels (sinusoids) in liver - causing blockage
- clinical presentation: Jaundice
Tender hepatomegaly
Fluid accumulation → rapid weight gain/ascites
how is Veno-Occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome (SOS) treated?
- prophylaxis
- defibrotide
what is lymphoma stage A vs B?
A - no ‘B’ symptoms
B - any one of ‘B’ symptoms
B symptoms - unexplained fever over 38, unexplained weight loss, drenching night sweats
what additional clinical investigations are needed for lymphoma?
- FBC - white blood cells eg lymphocytes
- organ functions - LFTs, RFTs indicate involvement
- viral screen - eg HIV, HepB/C
- G6PD - RBC function, treatment may cause hemolysis
- uric acid - high levels indicate cell breakdown
- LDH - elevated indicates more aggressive
- Beta- 2 microglobulin - as above
- ESR - may indicate inflammation, nonspecific
what are the treatment options for high grade lymphoma?
Immunochemotherapy, autograft
Radiotherapy
Allograft - transplanting stem cells
Check Point Inhibitors - immunotherapy targeting cancer and T-cells
BITE - Bispecific T-cell Engagers - t-cells attack cancer
CAR-T/NK - Chimeric Antigen Receptor engineered to be expressed in T-cells/Natural Killer cells
what are the main types of hodgkin lymphoma?
classical Hodgkin lymphoma - subclasses include Nodular sclerosis, Mixed cellularity
nodular lymphocyte-predominant Hodgkin lymphoma
what cells are found in hodgkin lymphoma?
Reed-Sternberg cell
what is the treatment for hodgkin lymphoma stage 1-2a vs 2b-4?
Stage 1-2A
- Short course combination chemotherapy - ABVD followed by radiotherapy
Stage 2B-4
- intensive chemotherapy, more cycles - ABVD
- radiotheraphy only selectively used
what is ABVD?
combinatoin of drugs in chemotherapy used to treat lymphoma
- doxorubicin, bleomycin, vinblastine, dacarbazine
what are the features of idolent NHL?
- incurable
- slow growing
what is diffuse large B cell lymphoma an example of?
aggressive/high grade non-hodgkin lymphoma
what are Myelodysplastic Syndromes?
blood cancers that affect the bone marrow
- Bone marrow cells fail to make adequate numbers of healthy blood cells
- risk factor for AML
what is Acute Myeloid Leukaemia characterised by?
- immature myeloid cell proliferation (defined as ≥20% “blasts”)
- bone marrow failure
what does a FBC show in myledoplastic syndromes?
- low blood count (red/white cells & platelets)
- Peripheral blood film demonstrates dysplastic features (e.g. hypogranular neutrophils)
what does a FBC show in acute myeloid lymphoma?
- white blood cells can be normal/high/low
- red blood cells, and platelets usually low
what are differential diagnosis of AML/ MDS?
- B12/ folate or mixed haematinic deficiency
- Infection (e.g. retroviral disease, herpesvirus)
- Medications
- Autoimmune
- Liver disease (e.g. cirrhosis)
what are important investigations in MDS/AML?
- history
- review previous FBC - is there a downward trend?
- FBC and blood film
- Haematinics (B12, folate, ferritin)
- high uric acid and LDH
- blasts in peripheral blood are key indicator
whatare the investigations for AML?
- Blood tests (full blood count & blood film)
- Bone marrow aspirate and trephine biopsy
- Immunophenotyping, Cytogenetics, Fluorescence in situ hybridisation (FISH), Molecular analyses
what conditions are associated with MDS/AML?
- anaemia
- neutropenia - low neutrophils
- thrombocytopenia low platelets
what is the treatment of AML?
- chemotherapy - Azacytidine
(Low dose subcutaneous cytarabine - non-curative for less fit people) - supportive measures eg fertility cryopreservation, blood transfusion
- hematopoietic stem cell transplantation after chemo for high risk relapse
what are the classifications of anaemia by cell size?
- Microcytic
- Normocytic
- Macrocytic
what is normal haemoglobin level in females/males?
females - 115-165 g/L
males - 130-180 g/L
what does Reticulocyte count show?
meaures immature red blood cells; measure of rate of red blood cell production
- for determining whether normocytic anaemia is resulting from increased destruction of RBCs or decreased production
- low count shows bone marrow isn’t producing RBC - bone marrow disease or iron deficiency
what in the normal amount of haemoglobin in cells?
27-33pg
what investigations are required when testing for anaemia?
- FBC with Mean Corpuscular Volume (MCV) to determine size to classify
- b12
- folate
- ferritin
- serum iron
- TIBC - total iron-binding capacity
- LFT/KFT
in folate/b12 deficiency, what needs to be started first?
b12
what are the causes for microcytic vs normocytic vs macrocytic anaemia?
- Microcytic:
Iron deficiency
Thalassaemias - Normocytic:
Chronic disease
Renal disease
(acute bleeding) - Macrocytic:
Folate deficiency
B12 deficiency
Haemolysis
Bone marrow disorders
what are the causes of iron deficiency?
- blood loss
- GI - coeliac
- menstrual
- dietary deficiency eg vegans
- pregnancy
what is normal MCV (Mean corpuscular volume)?
80-98fl
what are symptoms of anaemia?
Pallor
Fatigue
Breathlessness
Dizziness
Palpitations
Cold hands and feet
what is sickle cell disease?
single point mutation in beta globin gene
- autosomal recessive
- abnormal haemoglobin
- can block blood vessels causing ischaemia
how is sickle cell diagnosed?
- Sickle solubility test - quick test shows presence of HbS
- Haemoglobin electrophoresis - shows different Hb and HbS proportion
what are some complications of sickle cell?
- venoocclusive crisis - severe pain - analgesia
- stroke
- leg ulcers
- acute anaemia
- gallstones
- acute chest syndrome - high risk mortality
- Sequestration crisis
what is the treatment for sickle cell disease?
- preventative measures - eg warm, hydrated, vaccinated
- Hydroxycarbamide - increases HbF levels
- New drugs: crizanlizumab, voxelotor
- Regular blood transfusion - top-up and exchange
- allogeneic bone marrow transplant - potentially curative- rarely used due to high mortality
- gene therapy
what is Thalassaemia?
reduced Hb production
- alpha/ beta thalassaemia
- autosomal recesisve
- carriers - microcytic, may have mild anaemia
what is the management of thalassaemia (beta major)?
- red blood cell transfusion
- Monitoring of iron status and iron chelation therapy - avoid iron overload
- Folic acid (5mg daily)
- monitor organ systems
what is the difference between alpha thalassaemia major and minor?
minor - 1/2 genes affected, usually asymptomatic
major - death in utero
what is haemoglobin H disease?
- 3 alpha goblin genes affected
- moderate anaemia
- severity of symptoms varies
what are the 3 major criteria for diagnosing polycythaemia vera?
-
Hb over 16.5g/dL in men or 16g/dL in women
or increased red blood cell mass - bone marrow tri-lineage proliferation with pleomorphic mature megakaryocytes - increase in red cells, white cells, and platelets in the bone marrow
- presence of JAK2 mutation
what is the minor criteria for diagnosing polycythaemia vera?
- low serum erythropoietin level
- if normal bone marrow histology required
how is polycythemia vera distinguished between low vs high risk?
low risk - no history of thrombosis, under 50
high risk - history of thrombosis, over 50
what is thrombocytosis?
platelet levels are above normal
what is thrombocythaemia?
chronic myeloproliferative neoplasm (MPN) associated with an increase in number and size of circulating platelets
what is myelofibrosis?
- type of myeloproliferative neoplasm
- bone marrow disorder
what is the major criteria for myelofibrosis to be diagnosed?
- presence of JAK2, CALR, MPL or other clonal markers
- not meeting criteria for other myeloid neoplasms
- bone marrow fibrosis grade 2 or over
what is the minor criteria for myelofibrosis to be diagnosed?
- anemia with no other explanation
- Palpable Splenomegaly
- Increased Serum Lactate Dehydrogenase (LDH) Level
- leukocytosis
what are the treatment option for myelofibrosis?
- JAK inhibitors
- Erythropoietin
- blood transfusions
- Androgens to stimulate blood cell production
what does Erythropoietin most commonly treat?
anemia
what are the treatment options for CML(Chronic myelogenous leukemia)?
- Imatinib - tyrosine kinase inhibitor
- Interferon-alpha (IFN-α) immunotherapy
- Hematopoietic Stem Cell Transplantation - in aggressive cases
what investigations are required for CML?
- bone marrow biopsy
- karyotyping - BCR-ABL1 measured
- FBC
what cell do monocytes, basophils, eosinophils and neutrophils originate from?
myeloblast
- from common myeloid progenitor from hematopoietic stem cell
