WBC's and Haematological Malignancy Flashcards
What are the common causes of neutropenia and neutrophilia?
Neutrophilia: Bacterial Infection Tissue damage (burns, MI, PE) Inflammation (crohns, UC, RA, gout) Malignancy (chronic myeloid leaukaemia)
Neutropenia: Viral infection and severe bacterial infection (typhoid), Autoimmunity BM failure secondary to leaukaemia Genetic variation (black ethnicities) Alcoholism Diabetes
What are the common causes of lymphocytosis and lymphopenia?
Lymphocytosis:
Viral infections (particularly EBV, CMV and early HIV), Chronic infections (TB, toxoplasmosis),
CLL and some lymphomas,
Post-splenectomy.
Lymphopenia: HIV and autoimmunity Corticosteroids Chemotherapy Lymphoma Renal failure Transient following recent infection.
Outline the common causes of thrombocytopenia?
It is caused by:
Reduced production in the bone marrow
Excess destruction peripherally or sequestration in an enlarged spleen.
Causes of reduced production include: Bone marrow failure, Megaloblastic anaemia, Malignancies of the blood/marrow, HIV infection
Causes of excessive destruction:
Autoimmunity, SLE, CLL, DIC
Hypersplenism and splenomegaly will increase sequestration in the spleen.
Massive transfusion will cause thrombocytopenia by dilution.
Describe the symptoms of thromboycytopenia?
A purpuric rash and bleeding from mucosal membranes must be very low to cause symptoms.
How are leukaemias categorised?
Myeloid or lymphoid.
Acute or chronic.
How can leukaemias present?
General:
Malaise and anorexia
Lympathendopathy
Bone Marrow:
Anaemia (pallor, dizziness, dysopnea, tachycardia)
Recurrent/severe infections (fever of unknown origin)
Easy bruising/bleeding (may have petechiae)
Bone:
Unusual bone/joint pain
Abdo: Hepato-splenomegaly Early satiety (due to pressure on stomach from the spleen)
CNS: (in CNS metastasis) Headache Irritability or altered mental status Neck stiffness CN palsies
Define acute myeloid leukaemia?
It is a haematological malignancy of the myeloid precursor cells. It is classified as AML instead of myelodysplasia when there are greater than 20% of blast cells in the BM.
Note: Blast cells are abnormal immature WBC.
What are the prognostic indicators in AML?
Older patients have a poor prognosis, as well as those with complex karyotype mutations.
Chromosomal karyotypes which carry a good prognosis.
t(15:17)
t(8:21)
Inv(16)
How is AML treated?
Immediate chemotherapy after diagnosis (if safe to do so)
Strong IV chemotherapy in short sharp bursts. Younger patients have a better prognosis as they can tolerate high dose chemotherapy better.
Which cells are affected in ALL?
Malignancy of the lymphoid progenitor cells.
Usually B cell in origin but can be T cell.
Which age groups are commonly affected by ALL?
It is the most common childhood malignancy with the peak incidence being 4-5yo.
Worse prognosis in those less than 1 year or greater than 10yo.
How is ALL treated and what is the prognosis?
It is treated with the following chemotherapy regimen.
Remission induction.
Intensification including intrathecal chemo to prevent CNS relapse.
Maintenance for up to 3 years.
Prognosis is good with an 85% cure rate.
What are the factors which indicate a poorer prognosis in ALL?
Age: Less than 1yo or older than 10 yo. Very poor prognosis in the elderly.
Male gender.
Tumour load (measured by WBC) High risk = >50 x 109/L  Cytogenetic/molecular genetic abnormalities in tumour cells e.g. MLL rearrangement
Persistence of leukaemia blasts in the bone marrow after initial chemo

Minimal residual disease assessment (MRD) (submicroscopic levels of leukaemia detected by PCR)
High risk = high levels
CNS involvement
How does chronic myeloid leaukaemia present?
High WBC
Splenomegaly
Priapism
Which gene is strongly associated with CML?
Philladelphia Chromosome t(9:22)
How is CML treated?
Immediate treatment is with chemo, to reduced WBC count. Followed by prolonged control with hydroxycarbamide (Hydroxy-carb-amide)
New treatments include Imatinib which is a specific enzyme inhibitor used to induce remission.
Only cure is a bone marrow transplant.
How does chronic lympocytic leaukaemia usually present?
Usually incidental finding of high lymphocyte count followed by smudge cells on a blood film.
May also have:
- Lymphadenopathy
- Splenomegaly
- ITP or Autoimmune haemolytic anaemia
- BM supression
What is the prognosis of CLL?
Generally good but dependent on staging.
Stage A: Lymphocytosis only = 10yrs
Stage B: Lymphocytosis + lymphadenopathy in 3 areas = 5yrs
Stage C: Lymphocytosis + LN + low Hb or platelets = 2 years.
Reproductive rate of CLL cells is less than ordinary blood cells however there is defective apoptosis so they do not die.
How is CLL managed?
Usually watch and wait. Treatment is only for troublesome symptoms, bulk disease or marrow failure.
Treatment involves:
- Corticosteriods for effective short term treatment
- Mild chemo/combination chemo
Summarise the following in terms of age affected and prognosis: ALL, AML, CML and CLL?
ALL: Children, generally good prognosis due to effective chemo.
AML: Any age but more common in adults associated with specific gene abnormalities. Relatively good prognosis in children, prognosis gets worse with age.
CML: Any age but rare in children. Associated with the Philadelphia chromosome. Traditionally a poor prognosis but new medications have improved survival.
CLL: Very common in the elderly. Good prognosis as very slow growing.
What is the difference between Hodgkins and Non-Hodgkins lymphoma?
They are both malignant tumours of the lymphatic system.
Hodgkins lymphoma are characterised by the presence of multinucleted Reed-sternberg cells; which are not present in NHL
Symptomatically and prognostically they are also different.
Which age groups are most likley to be affected by Hodgkins lymphoma?
2 age peaks: teens/early twenties and the elderly
Which infection is Hodgkin’s lymphoma associated with?
EBV
How does Hodgkins lymphoma present?
Usually presents with asymptomatic lympadenopathy.
25% of patients present with B symptoms:
- Weight loss greater than 10% in 6 months
- Drenching night sweats
- Fevers greater than 38
In roughly 10% of patients they complain of alcohol induced pain in their lymph nodes.
What is the staging classifaction used in HL and what are the stages?
Ann Arbor Classification:
I: One nodal area
II: Two or more nodal areas on one side of the diaphragm
III: Nodal areas on both sides of the diaphragm
IV: Extra nodal spread (including marrow)
Which age group are most likely to suffer from NHL?
Over 50’s however is more common in young children than Hodgkins
Overall is much more common than hodgkins lymphoma. NHL is an umbrella term for several different disease entities showing malignant growth of lymphoid cells.
Which viruses are associated with NHL?
EBV (also associated with HL)
Human T-cell leukaemia virus type 1 (HTLV-1)
Hepatitis C
How does NHL present?
NHL predominantly affects lymph nodes and can present as localised lymph node disease in the:
- head/neck/abdomen (B cell)
- mediastinal mass (T cell) and may also cause bone marrow infiltration.
May also cause hepato/splenomegaly.
May also cause symptoms due to pressure effect such as pain and obstruction.
In high grade disease there will be rapidly growing bulky lymphadenopathy and it may present as metastasis in the GI, BM or CNS.
How should you investigate for lymphoma?
Include on your differential, lymphoma presentation is very varied therefore any mysterious illness could be a lymphoma.
If scan or examination suggests lymphadenopathy consider biopsy if no explanation.
No biopsy no diagnosis (BM biopsy is not diagnostic)
CT for staging.
How are NHL staged?
Using the same staging system as Hodgkins Lymphoma.
Ann Arbor staging:
I: One nodal area
II: Two or more nodal areas on one side of the diaphragm
III: Nodal areas on both sides of the diaphragm
IV: Extra nodal spread (including marrow)
As well as this they are also graded as high or low depending on how aggressive it is.
Describe the prognosis of high and low grade NHL’s?
High grade:
Poor prognosis if untreated but initially responds well to chemo as it is fast growing, many relapse however.
Low grade:
Slow growing so good 10 year survival but they have a poor response to chemo and are often uncurable. Also have the potential to transform into high grade lymphoma.
What are the different types of low grade NHL?
Follicular lymphoma: Common low grade lymphoma (often watch and wait)
Mantle cell lymphoma: Common in GI tract
Marginal zone lymphoma: Common extranodal NHL. Associated with H.pylori infection
What are the different types of high grade lymphoma?
Burkitts Lymphoma
Diffuse large cell lymphoma (commonest NHL) may arise from transformation of a low grade
What are MALTomas?
Mucosa-associated lymphoid tissue also known as Peyer’s patches (found in the small intestine)
Chronic immune stimulation by H.pylori can cause them to transform into a MALToma.
Further transformation can lead to them becoming Marginal Zone Lymphomas.
What is myeloma?
It is a malignant proliferation of plasma cells which infiltrate the bone marrow.
Diagnostic criteria require 2 of the following to be met:
- More than 10% plasma cells in the BM
- Detectable paraprotein in the blood or urine
- Lytic lesions on a skeletal survery
What is the condition called if there are just paraproteins detected?
Monoclonal Gammopathy of Undetermined Significance (MGUS)
What is the typical presentation of a patient with myeloma?
Typically a disease of the elderly.
Presenting with:
- Back pain
- Anaemia
- Raised ESR
Poor prognosis
Describe the symptoms of myeloma based on symptoms?
BM:
- Anaemia
- Thrombocytopenia
- Immune supression of normal Igs
Blood:
-Hyperviscosity syndrome due to high paraprotein levels
NS:
- Hypercalcaemia
- Spinal cord compression
Renal: Renal failure due to: -Bence Jones proteins (paraprotein) are toxic to renal tubules -Amyloidosis (can occur in myeloma) -Increased no of UTI's -Dehydration secondary to hypercalcaemia
What is hyperviscosity syndrome?
Caused by excess plasma proteins.
Stickier blood, causes symptoms such as:
- fatigue
- headache
- confusion
May eventually cause stroke/MI
Severe cases are treated with plasmapheresis (bleeding)
Note: Anaemia lowers blood viscosity therefore in patients with hyperviscosity syndrome note that transfusions can be extra risky
How is Myeloma treated?
Dependent on age and fitness:
- Young and fit induce remission with IV chemo, once in remission stem cell rescue
- Elderly usually treat with gentle chemotherapy.
Radiotherapy can be excellent for pain relief of lytic bone lesions.
What is Waldenstroms Macroglobulinaemia?
Presence of IgM paraprotein in blood or urine.
Main health risk is hyperviscosity syndrome.
What is myelodysplasia?
Disordered maturation of blood cells in the bone marrow.
May affect any cell lineage.
How is myelodysplasia treated?
Treatment is supportive:
Anaemia: transfuse
Low platelets: Tranexamic acid, platelet transfusion for active bleeding
Neutropenia: Abx
Prognosis is dependent on age, general well being and degree of cytopenia
