Haematology Flashcards
What is a myeloma?
A malignant proliferation of the Plasma cells (Type of B lymphocytes)
Define multiple myeloma (MM)?
Malignant proliferation of plasma cells (B lymphocytes) accumulating in the bone marrow that affects multiple areas of the body
What is the second most common haematological cancer?
Multiple Myeloma
What is the pathogenesis of Multiple Myeloma?
Malignant proliferation of plasma cells (B lymphocytes) accumulating in the bone marrow
This leads to overproduction of IgG/IgA or Ig fragment (monoclonal paraprotein) and underproduction of others
Causes dysfunction of many organs (especially the kidney), bone marrow failure, destructive bone disease and hypercalcaemia
Characterised by excess secretion of a monoclonal antibody
What is a paraprotein?
Paraprotein → abnormal immunoglobulins produced by monoclonal plasma cells
They can be intact immunoglobulins (usually IgG, IgA or IgM) or parts of immunoglobulins (usually light chains, very rarely heavy chains)
What are the main paraproteins produced in multiple myeloma?
Typically excess production of 1 specific type of Ig.
55% are IgG
20% are IgA.
What are the preceding steps before established multiple myeloma?
Development of Mammyloid gammopathy of undetermined significance (MGUS)
Smouldering myeloma
What is Mammyloid Gammopathy of Undetermined significance (MGUS)?
where there is over proliferation of plasma cells leading to an excess of a single type of antibody or antibody components without other features of myeloma or cancer.
This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear.
May progress to MM and patients are often routinely monitored.
What is Smouldering Myeloma?
where there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS
What is Waldenstrom’s macroglobulinemia
Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.
What is the rate of progression of MGUS to MM?
1% per year
What is the clinical presentation of multiple myeloma related to?
Infiltration of plasma cells
Secretion of monoclonal antibodies
What are the Risk Factors of Multiple Myeloma?
Older age
Male
Black African ethnicity
Family history
Obesity
Give some symptoms of Myeloma?
Tiredness
Bone/back pain
Infections
What are the signs and symptoms of multiple myeloma?
OLD CRAB:
Old - 70+
C - Hypercalcaemia (& associated symptoms)
R - Renal Failure (hypercalcaemia causes calcium oxalate renal stones and immunoglobulin light chain kappa deposition is nephrotoxic)
A - Anaemia (Bone Marrow Infiltration causing; Neutropenia (infections), Thrombocytopenia (bleeding)
B - Bone Lesions - increased osteoclastic activity - Pepperpot Skull
How does bone disease arise in multiple myeloma?
Proliferation in bone marrow
Lytic lesions
Fractures
How does impaired renal function arise in multiple myeloma?
Kappa Immunoglobulin light chains (Bence Jones Protein) are nephrotoxic.
& Hypercalcaemia
Why may Renal disease worsen the effects of Anaemia in MM?
Renal disease can lead to EPO deficiency contributing to the anaemia
How does hypercalcaemia arise in multiple myeolma?
Multiple myeloma-induced bone demineralisation and bone resorption
How does recurrent/persistent bacterial infection arise in multiple myeloma?
Immune dysfunction and hypogammaglobulinemia
Suppression of normal plasma cell function
Why does anaemia occur in multiple myeloma?
The cancerous plasma cells invade the bone marrow.
This is described as bone marrow infiltration.
This causes suppression of the development of other blood cell lines leading to:
Anaemia (low red cells),
Neutropenia (low neutrophils)
Thrombocytopenia (low platelets).
What initial diagnostic investigations are ordered in someone with suspected multiple myeloma?
FBC - anaemia and raised ESR
Serum and urine electrophoresis – B2 microglobulin
Blood film – Rouleaux formation (aggregations of RBCs)
Bence Jones protein in urine
BM aspiration shows excess plasma cells
X-ray – shows pepperpot skull and lyses in long bones, pelvis and spine
What are the Genetics of Multiple Myeloma?
Commonly caused by the Translocations of chromosomes 11 and 14
t(11:14)
What Investigations are needed to confirm a diagnosis of Multiple Myeloma?
Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease.
>10% plasma cells
Imaging is required to assess for bone lesions.
X-ray – shows pepperpot skull and lyses in long bones, pelvis and spine
What is indicative of MM on bone marrow biopsy?
> 10% plasma cells
What bloods results would be indicative of multiple myeloma?
FBC - marrow failure
ESR - raise
Blood film - Rouleaux formation (RBC Aggregations)
U&Es - raised urea and creatinine
Hypercalcaemia
What are some important differential diagnoses of Multiple Myeloma?
MGUS
What is the treatment for MGUS and asymptomatic myeloma?
Watch and wait.
What is the principle behind treatment of MM?
Multiple myeloma is an incurable condition → treatment aims to increase periods of disease remission
What is the first line treatment for multiple myeloma?
A combination of chemotherapy with:
Bortezomid - proteasome inhibitor
Thalidomide
Dexamethasone - steroid
Bisphosphonates - zoledronate
Analgesia - (NOT NSAIDs)
What else may you consider to treat multiple myeloma?
Stem cell transplant
Bisphosphonates - bone protection
Name the 3 broad categories of red cell disorders.
- Haemoglobinopathies.
- Membranopathies.
- Enzymopathies.
What is a haemoglobinopathy?
Deficiency related to quality or quantity of haemoglobin production
What is a membranopathy?
Deficiency related to red blood cell membrane protein
What is an enzymopathy?
Deficiency related to RBC enzyme synthesis, leads to shortened lifespan due to oxidative stress
What is the normal range for haemoglobin?
120-180g/L
What is normal adult haemoglobin made of?
HbA1:
2 alpha and 2 beta chains.
What is foetal haemoglobin made of?
HbF:
2 alpha and 2 gamma chains.
What are the common Symptoms of Anaemia?
Fatigue
Lethargy
Dyspnoea – difficulty or laboured breathing
Palpitations
Headache
What are the common signs of anaemia?
Pale skin
Pale mucous membranes – nose and eyelids
Systolic flow murmur
Tachycardia (compensatory to meet demand)
What are the common consequences of anaemia?
Reduced O2 transport
Tissue hypoxia
Compensatory changes:
Increased tissue perfusion
Increased O2 transfer to tissues
Increased RBC production
What is haemoglobin S?
Haemoglobin S is a variant of Hb arising from a point mutation in the beta globin gene.
The mutation leads to a single amino acid change, valine -> glutamine.
What is sickle cell disease?
Auto recessive disorder
A Hb disorder of quality; polymerisation of HbS results in characteristic sickle shaped RBCs
What is the genetics of Sickle Cell disease and what ethnicity is at increased risk?
Afro-Caribbean
Autosomsal Recessive
1 in 4 chance of disease,
50% chance of being a carrier
1 in 4 chance of being disease free
What are the types of Sickle Cell disease based on Inheritance?
- Sickle cell anaemia (HbSS) = inheritance of 2 abnormal sickle genes
- Sickle cell disease (HbSC) = Inheritance of one abnormal sickle gene and second haemoglobin variant of the beta chain that causes sickling. E.g. haemoglobin C
- Sickle cell trait (HbS) = Inheritance of one abnormal sickle gene. Sickle carrier.
- Sickle-thalassaemia (H
What is the lifespan of a Sickle Cell?
5-10 days - described as haemolytic
What is the Pathophysiology of Sickle Cell Anaemia?
- Point mutation of the HBB B globin gene (valine for glutamic acid) resulting in a HbS variant
- Under stress (cold/infection/dehydration/hypoxia/acidosis), the RBCs become deoxygenated and the HbS chains polymerises causing the RBCs to become rigid and sickle
- Causing chronic intravascular haemolysis and tissue infarction
- This leads to vaso-occlusion and significantly shortens the life span of an RBC to 10-20 days
What can precipitate sickling in Sickle Cell Anaemia?
Trauma
Cold
Stress
Exercise
infection
dehydration
hypoxia
acidosis
Why does Sickle Cell Anaemia not present until after 6 months of age?
HbF is not affected by sickle cell anaemia as it is made up of 2 alpha and 2 gamma chains.
Prior to 6 months of age the body still produces HbF
What are reticulocytes?
Immature RBCs that still have RNA material.
Their percentage increases in haemolytic anaemia
What effect does Sickle Cell Anaemia have on reticulocyte count?
Raised - 2-3% (normally 0.45-1.8%)
Why is reticulocyte count raised in Sickle Cell Anaemia?
Sickle cell disease is haemolytic - increased degradation of RBC’s
What is the pathogenesis of sickle cell disease?
Point mutation in the Beta globin gene (GAG to GTG) swapping glutamic acid for valine.
This causes irreversible RBC sickling which makes the RBC fragile.
A decreased surface area also means the RBCs are less efficient.
What are the symptoms of Sickle Cell disease?
Jaundice - haemolytic anaemia releasing bilirubin
Acute pain in hands and feet (vaso-occlusion)
+ complications of anaemia
Give 4 acute complications of sickle cell disease.
- Vaso-occlusive painful Crisis
- Mesenteric Ischaemia
- Splenic Sequestration crisis - blocked blood flow to spleen
- Infections - due to hyposlenysm
Give 3 chronic complications of sickle cell disease.
- Renal impairment.
- Pulmonary hypertension.
- Joint damage.
What are some complications of Sickle cell disease?
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
What is Vaso-occlusive Crisis (AKA painful crisis) in sickle cell disease?
Sickle shaped blood cells clogging capillaries causing distal ischaemia.
This can lead to dactylitis
It is associated with dehydration and raised haematocrit.
Symptoms are typically pain, fever and those of the triggering infection.
What is Splenic Sequestration Crisis?
Sickled Red blood cells blocking blood flow within the spleen.
This causes an acutely enlarged and painful spleen.
The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock).
What is the significance of parvovirus for someone with sickle cell disease?
Common infection in children (URTI), leading to decreased RBC production
What are the diagnostic tests for Sickle cell disease?
Newborn Blood Spot test for Sickle cell
FBC:
Low Hb
High reticulocyte count
Blood film – sickled erythrocytes, Howell Jolly bodies
Hb electrophoresis for differential diagnosis – Hb SS present and absent Hb A confirms diagnosis of sickle cell disease
What is the management of Sickle Cell Disesae?
Supportive:
Folic acid
Aggressive analgesia i.e. opiates
Oxygen
Fluids
Disease modifying:
Hydroxycarbamide/Hydroxyurea – increases HbF concentrations
Transfusion
Stem cell transplant
If hyposplenic:
Prophylactic antibiotics
Pneumococcal and meningococcal vaccination
What are the treatments of acute complicated attacks in sickle cell disease?
IV fluids
Analgesia (Opiates)
O2
What are the long term treatments for sickle cell disease?
Avoid Dehydration
Hydroxycarbamide/Hydroxyurea - stimulates HbF production
Blood transfusion
Bone marrow transplant
What is the relationship between Sickle cell disease and Malaria?
Having one copy of the sickle cell gene reduces the severity of malaria and is protective.
There is a high proportion of the population in Africa & other malaria associated areas with at least one sickle cell gene.
What is the most common cause of death in adults with Sickle Cell Disease?
Pulmonary HTN and chronic lung disease most common cause of death in adults with SCD
What is thalassaemia?
An autosomal recessive disorder of haemoglobin quantity.
There is reduced synthesis of one or more globin chains leading to a reduction in Hb -> anaemia.
Degree of anaemia depends on the type of mutation
Px with defects in Alpha chain synthesis have alpha Thalassaemia
Px with defects in Beta chain synthesis have beta Thalassaemia
If someone has beta thalassaemia do they have more alpha or beta globin chains?
They have very few beta chains, alpha chains are in excess.
Which is more common, alpha or beta thalassaemia?
Beta thalassaemia is more common
What are some potential signs and symptoms of Thalassaemia?
Microcytic anaemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
Why do you get splenomegaly in thalassaemia?
RBCs in thalassaemia are more fragile and break down easily.
In thalassaemia the spleen collects all the destroyed red blood cells and swells, resulting in splenomegaly.
What are mutations that result in alpha Thalassaemia?
4 genes on chromosome 16
Deletion mutations
What is produced in alpha thalassaemia as a result of the decreased alpha chains?
Excess beta chains form an unstable beta tetramer (HbH)
This is a poor carrier of O2
Where is alpha thalassaemia most prevalent?
- Sub-Saharan Africa
- Middle East
- Mediterranian
- Areas of Asia
What mutations cause Alpha Thalassaemia?
4 genes control production of alpha globin chains. α thalassaemia is caused by gene deletions (unlike B which is due to gene defects/point mutations)
1 deletion: blood picture normal.
2 deletions: Asymptomatic with possible mild microcytic anaemia.
3 deletions: Common in parts of Asia. Patients have low levels of HbA and Hb Barts. Severe haemolytic anaemia, and splenomegaly. Sometimes transfusion dependent.
4 deletions = no a-chain synthesis, only Hb Barts present. Hb Barts CANNOT CARRY OXYGEN and is incompatible with life. (Infants stillborn; they are pale, oedematous with huge livers and spleens.
What is the Pathogenesis of Beta Thalassaemia?
In homozygous ß-thalassemia 🡪 little/no normal ß chain production 🡪 therefore, EXCESS α chain production 🡪 α chains combining with whatever ß, 𝛿 or γ chains available 🡪 increased production of HbA2 and HbF 🡪 resulting in ineffective erythropoiesis and haemolysis
What are mutations that result in Beta Thalassaemia?
2 genes on chromosome 11
Can have abnormal functional genes or deletion genes that are non functional resulting in different types of Beta Thalassaemia
What are the 3 clinical syndromes of Beta Thalassaemia?
Thalassaemia Minor
Thalassaemia Intermedia
Thalassaemia Major
What is Thalassaemia Minor?
One abnormal and One functional beta globin gene
Asymptomatic heterozygous carrier state
Mild/absent anaemia – low MCV and hypochromic
Iron stores and ferritin normal
What is Thalassaemia Intermedia?
Either:
2 defective beta globin genes - retain some function
OR
1 defective and 1 deletion gene
Moderate anaemia – patients don’t require transfusions
Splenomegaly, bone abnormalities, recurrent leg ulcers and gallstones
What is Thalassaemia Major?
Px with Homozygous Beta globin deletion genes.
No functioning beta globin genes
Presents in 1st year of life with severe anaemia (Cooley’s anaemia) – failure to thrive and recurrent infections
Bony abnormalities due to hypertrophy of ineffective BM e.g. skull bossing, thalassaemic faces with an enlarged maxilla and prominent frontal and parietal bones (hair on end sign on skull XR)
Hepatosplenomegaly – due to haemolysis
What are the diagnostic investigations for Thalassaemia?
Alpha - Hb electrophoresis – shows increased HbF and absent/low HbA
Beta - Blood film - hypochromic and microcytic anaemia, target cells visible on film
Irregular and pale RBCs
Increased reticulocytes and nucleated RBCs in peripheral circulation
Skull XR – hair on end sign, enlarged maxilla
Why is Iron overload an issue in Thalassaemia?
Iron overload occurs in thalassaemia as a result of faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
How is Iron overload in Thalassaemia managed?
Monitored Serum Ferritin levels
Limiting transfusions
Iron Chelation - SC desderrioxamine
What is the key clinical symptom of Beta Thalassaemia?
Chipmunk Face - due to enlarged forehead and cheekbones due to decreased RBCs and extramedullary haematopoiesis
What is the treatment for Thalassaemia?
Regular Blood transfusions
Iron Chelation - prevent Iron overload (as thats a risk of recurrent transfusions)
Splenectomy
Folate supplements
Bone marrow stem cell transplant
What is a potential Curative option for thalassaemia?
Bone marrow stem cell transplant
Describe the inheritance pattern for Membranopathies
Autosomal dominant
Name two most common Membranopathies
Spherocytosis (horizontal deformity) - more severe, present neonatal jaundice and haemolysis
Elliptocytosis (vertical deformity)
Describe the pathophysiology of Membranopathies
Deficiency of red cell membrane proteins caused by genetic lesions leading to haemolytic anaemia.
What are the common clinical features of Membranopathies?
Jaundice
Anaemia
Splenomegaly
What is Hereditary Spherocytosis?
Deficiency in structural membrane protein Spectrin
Makes RBCs more spherical and rigid
Mistaken to be damaged and therefore prematurely destroyed by the spleen
Causes Splenomegaly
What are the symptoms of Hereditary Spherocytosis?
General Anaemia
Neonatal Jaundice
Splenomegaly
50% have Gallstones
What is the investigations of Hereditary Spherocytosis and Elliptocytosis?
Direct Coombs Negative (positive = Autoimmune Haemolytic Anaemia)
FBC and blood film:
Normocytic Normochromic
Increased Reticulocytes + Spherocytes
What is the treatment for Hereditary Spherocytosis?
Splenectomy
Folic Acid
Neonatal Jaundice - Phototheraphy
Name a common Enzymopathy.
Glucose-6-Phosphate Dehydrogenase deficiency
What is G6PD Deficiency?
X linked recessive enzymopathy causing 1/2 RBC lifespan and RBC degradation
What is the pathology of G6PD Deficiency?
G6PD vital in hexose monophosphate shunt which maintains glutathione in reduce state. Glutathione protects the RBC from oxidative crisis
Therefore in deficiency the RBCs are easily damaged by oxidative stress.
Why does a deficiency in glucose-6-phosphate dehydrogenase lead to shortened red cell lifespan?
G6PD is required for glutathione synthesis
Glutathione protects Red blood cells against oxidative damage
How does G6PD deficiency present?
Mostly asymptomatic unless precipitated by oxidative stressor causing an attack:
Back pain
Chronic haemolytic anaemia
Acute haemolysis
Rapid anaemia - pallor, fatigue, SOB,
Jaundice + Dark urine
Caused by
Ingestion of fava beans
Common drugs – quinine, sulphonamides, quinolones and nitrofurantoin
What is the diagnostic investigations for G6PD Deficiency?
Reduced G6PD levels
FBC - anaemia and raised reticulocytes
Blood film:
Normal in between attacks
Attack - increased reticulocytes and HEINZ bodies and BITE cells
What is the treatment for GP6D Deficiency?
Avoid Precipitants - Oxidative drugs
Blood transfusions when attacks come on.
What precipitants can lead to attacks of GP6D Deficiency?
Naphthalene
Anti-malarials
Aspirin
FAVA beans
Nitrofurantoin
What are lymphomas?
Malignant proliferation of lymphocytes which accumulate in lymph nodes 🡪 lymphadenopathy
What are the two main categories of lymphoma?
Hodgkin’s Lymphoma - a specific disease
Non-Hodgkin’s Lymphoma - encompasses all other lymphomas
What are the main Lymph node sites?
Cervical Lymph Nodes
Axillary Lymph Nodes
Inguinal Lymph Nodes
What are some Potential causes of Lymphoma?
Primary Immunodeficiency - Ataxia Telangiectasia
Secondary Immunodeficiency - HIV, Transplant recipients
Infection - EBV, HIV, HTL virus, H-pylori
Autoimmune disorders - SLE
What is the pathophysiology of Lymphoma?
Not well understood
Thought to be multifactorial - Genetic factors + Environment
Impaired Immunosurveillance
Infected B cells escape regulation and proliferate
What are the general symptoms of Lymphoma?
Lymphadenopathy
SVC obstruction
B symptoms
Weight loss
Appetite loss
Night sweats
Fever
What is Hodgkin’s Lymphoma?
Cancerous Proliferation of Lymphocytes triggered by infection
Bimodal age distribution - affects teens (13-19) and elderly (75+)
Associated with EBV infection
What are the 2 types of Hodgkin’s Lymphoma?
Classical - Reed Sternberg cells with mirror-Image nuclei
Nodular Lymphocyte Predominates Hodgkin’s Lymphoma (NLPL) - Reed Sternberg cell variant - Popcorn cell
What are the risk factors for Hodgkin’s Lymphoma?
HIV
Male
20-30s or >55
previous Epstein-Barr Virus infection
Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
Family history - affected sibling
How does Hodgkin’s Lymphoma normally Present?
Lymphadenopathy - non-tender, feel rubbery
Pain in lymph nodes when drinking alcohol.
B symptoms - Fever, Weight loss, Night sweats
What are the B Symptoms associated with Lymphoma/other haematological disorders?
Fever
Weight Loss >10% in 6 months
Night Sweats
What other symptoms may be associated with Hodgkin’s Lymphoma?
Fatigue
Pruritus’ (itching)
cough
SOB
Abdominal Pain
Recurrent infections
What are the diagnostic investigations for Hodgkin’s Lymphoma?
Lymph Node Biopsy - Reed Sternberg cell positive with mirror image nuclei
FBC:
Anaemia - Low Hb
Increased ESR
Lactate Dehydrogenase
CXR - widened mediastinum
CT/MRI - Fir staging and diagnostics
What type of Biopsy is done to Diagnose Lymphoma?
Core Needle Biopsy
Lymph Node Excision
What are Reed Sternberg cells?
Abnormally large B cells with multiple nuclei that are the key finding on lymph node biopsy in Hodgkin’s Lymphoma.
What is the Ann Arbor Staging system?
Used for Staging Hodgkin’s and Non-Hodgkin’s Lymphoma
Stage 1 - Single Lymph node region
Stage 2 - In more than 1 lymph node region but same side of the diaphragm
Stage 3 - Lymph nodes both above and below Diaphragm affected
Stage 4 - Widespread involvement including other non-lymphatic organs (lungs/liver)
A = NO B symptoms
B = HAS B symptoms
What other organs may be affected in Stage 4 Hodgkin’s Lymphoma?
Blood
Bone Marrow
Liver
Spleen
What is used to stage lymphomas using the Ann Arbor staging system?
CT/MRI/PET scans
What is the Treatment for Hodgkin’s Lymphoma?
ABVD Chemotherapy:
Adriamycin
Bleomycin
Vinblastine
Dacarbazine
(Potentially Radiotherapy)
What are the different courses of treatment for Hodgkin’s Lymphoma?
Stage IA - IIA (< 3 areas involved):
Short course ABVD
Stage IIA - IVB (> 3 areas involved):
Longer courses of ABVD
What is the Aim of Treatment for Hodgkin’s Lymphoma?
To cure the condition
Usually successful however there is a risk of relapse and SE of treatment.
What are the side effects of Chemotherapy?
Infertility
Nausea
Alopecia
Vomiting
Constipation/diarrhoea
Rash
What are the Side effects of Radiotherapy?
IHD
Second malignancies
Hypothyroidism
What are the side effects of:
Anthracyclines
Bleomycin
Vinka alkaloids
Anthracyclines – cardiomyopathy
Bleomycin – lung damage
Vinka alkaloids – peripheral neuropathy
Daunorubicin - cardiotoxic
What are some side effects of Hodgkin’s Lymphoma Treatment?
Chemotherapy:
Alopecia
N+V
Myelosuppression & BM failure = Infection
Radiotherapy - Increased risk of second malignancies
What is Febrile Neutropenia?
A condition marked by Fever and very low neutrophil numbers in the blood.
Massive risk in Px who have had recent/High dose Chemo (or on Carbimazole)
What is the treatment for Febrile Neutropenia?
Immediate Broad Spec Antibiotics
(Amoxicillin + Fluoroquinolone)
What is Non-Hodgkin’s Lymphoma?
malignant clonal expansion of lymphocytes which occurs at different stages of lymphocyte development.
All lymphomas without Reed Sternberg cells.
80% are B cell origin and 20% T cell origin.
Give some Key Non-Hodgkin’s Lymphomas
Low Grade - Follicular
High Grade - Diffuse Large B cell Lymphoma
Very high Grade - Burkitt Lymphoma
What are the risk factors of Non-Hodgkin’s Lymphoma?
> 75 yrs
HIV
Epstein-Barr Virus
H. pylori (MALT lymphoma)
Hepatitis B or C infection
Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes
Family history
What are some Specific Symptoms of Burkitt Lymphoma?
Linked to EBV infection.
Causes Massive Jaw Lymphadenopathy in children
What are the symptoms of Non-Hodgkin’s Lymphoma?
Variable symptoms due to the range of subtypes however Px generally present in a similar way to Hodgkin’s Lymphoma:
Painless Rubbery Lymphadenopathy
B Symptoms
Lymph nodes NOT Painful with Alcohol.
What are the Diagnostic tests for Non-Hodgkins Lymphoma?
Lymph Node Biopsy - No RS/Popcorn Cells confirms NHL lymphoma
CT/MRI for Ann Arbor Staging
What is the Treatment for Non-Hodgkin’s Lymphoma?
R-CHOP:
Rituximab - Targets CD20 on B cells
Cyclophosphamide
Hydroxy-Daunorubicin
Vincristine (Oricovin)
Prednisolone
+ radiotherapy
Describe the prognosis of low-grade Non-Hodgkin’s Lymphoma
Slow growing, advanced at presentation, incurable
Median survival; 10 years
Describe the prognosis of high-grade Non-Hodgkins Lymphoma
Nodal presentation; presents early than low grade, therefore often curable
Aggressive - can make patient very unwell.
How does the treatment for low and high-grade Non-Hodgkins Lymphoma, differ?
In general, if the patient is symptomless - watch and wait.
Low grade; no chemotherapy may be required - radiotherapy may be curative in localised disease.
If symptomatic, Chemotherapy radiotherapy, combination chemotherapy and mAb
High Grade:
Early - Short course R-CHOP
Advanced - Combination R-CHOP + Rituximab
How does the treatment differ between High grade Non-Hodgkin’s lymphoma that is detected early and late?
Early - 3 months of RCHOP with radiotherapy
Late - 6 months of RCHOP with Radiotherapy
What is Myelodysplastic Syndrome?
Myelodysplastic syndrome is caused by the myeloid bone marrow cells not maturing properly and therefore not producing healthy blood cells.
There are a number of specific types of myelodysplastic syndrome.
What happens to the blood cell maturation in Myelodysplastic Syndrome?
Causes low levels of blood components that originate from the myeloid cell line:
Anaemia - Low RBC
Neutropenia - Low neutrophils
Thrombocytopenia - Low platelets
What do patients have an increased risk of developing if they have Myelodysplastic Syndrome?
Acute Myeloid Leukaemia (AML)
How does Myelodysplastic Syndrome Present?
May be Asymptomatic and the diagnosis is made incidentally
May present with symptoms of:
Anaemia - fatigue, pallor, SOB
Neutropenia - Recurrent/severe infections
Thrombocytopenia - Bleeding/bruising
What are the diagnostic investigations for Myelodysplastic syndrome?
FBC - Low RBC, Neutrophils, Platelets
Blood Film - Blasts present (immature myeloid derived progenitors)
Bone marrow aspiration biopsy
What is the management of Myelodysplastic Syndrome?
Watchful Waiting
Supportive Treatment with blood transfusions if severely anaemic
Chemotherapy
Stem Cell Transplant
Define Leukaemia?
The malignant Proliferation (Cancer) of a particular line of haematopoietic stem cells (blast cells) in the bone marrow. This causes unregulated production of certain types of blood cells.
What is the pathophysiology of Leukaemia?
A genetic mutation in one of the precursor cells (myeloblast or lymphoblast) in the bone marrow leads to excessive production of a single type of abnormal white blood cell.
This can lead to suppression of other cell lines causing underproduction of those types.
This causes Pancytopenia - Combination of anaemia, leukopenia and thrombocytopenia
Why is there suppression of other cell lines in leukaemia?
Rapid proliferation of one leukocyte takes up lots of space in the bone marrow.
This leaves less space for functioning cells to be produced.
What are the 4 main types of leukaemia?
Acute Myeloid Leukaemia (AML)
Acute Lymphoblastic Leukaemia (ALL)
Chronic Myeloid Leukaemia (CML)
Chronic Lymphoblastic Leukaemia (CLL)
What age ranges are at increased risk of the different types of leukaemia?
Mnemonic: ALL CeLL mates have CoMmon AMbitions
under 5 and over 45 - ALL
Over 55 - CLL
Over 65 - CML
Over 75 - AML
What age group does ALL commonly affect?
children under 5
What clinical symptoms are associated with Leukaemia?
Fatigue - anaemia
Fever + infections
Failure to thrive (children)
Pallor due to anaemia
Petechiae and abnormal bruising due to thrombocytopenia
Abnormal bleeding - thrombocytopenia
Lymphadenopathy
Hepatosplenomegaly