Haematology Flashcards
What is Myeloma?
Malignant disease of bone-marrow plasma cells
What happens pathophysiologically in Myeloma?
Clonal Expansion of abnormal proliferating plasma cells lead to a monoclonal paraprotein. This produces paraproteinaemia
What may be found in the urine of a patient with Myeloma?
Bence-Jones Protein - Excretion of light chains in the urine
What are some clinical features of Myeloma?
Bone Destruction
Bone Marrow infiltration
Kidney Injury
Recurrent infections
What causes Bone Destruction in Myeloma?
Increased osteoclastic activity in the absence of osteoblast activity
What can bone marrow infiltration in Myeloma lead to?
Anaemia
Neutropenia
Thrombocytopenia
What causes Kidney Injury in Myeloma?
Light chain deposition in the renal tubules
Hypercalcaemia
Hyperuricaemia
NSAID use
Why does Myeloma lead to recurrent infections?
Reduced levels of usual immunoglobulins
What are some symptoms of Myeloma?
Bone pain - Often backache due to vertebral involvement
Symptoms of Anaemia
Recurrent infections
Symptoms of Renal Failure
Symptoms of Hypercalcaemia
Symptoms of Hyperviscosity secondary to Thrombocytopenia
Which blood investigations are appropriate for suspected Myeloma?
FBC - Hb, WCC and Platelets either normal or low
ESR - Elevated
U+E - Kidney Injury
Serum Ca - Raised
What may a blood film demonstrate in Myeloma?
Aggregates of Red Blood Cells - Rouleaux
What will serum protein electrophoresis demonstrate in Myeloma?
Monoclonal Paraprotein Band with Immune Phoresis
Which Radiological investigation is appropriate in suspected Myeloma?
Skeletal Survey
CT/MRI
How is the diagnosis of Myeloma confirmed?
One of either:
Significant Paraproteinaemia
Increased Bone Marrow Plasma Cells on biopsy
What are some general supportive measures to manage Myeloma?
Correct Anaemia with Transfusion +/- EPO
Prompt Abx for infections
Bone Pain - Radiotherapy +/- Chemotherapy
Orthopaedic intervention for at-risk bones
Which specific therapies can be used in Myeloma?
Thalidomide
Cyclophosphamide
What is Acute Leukaemia?
Uncontrolled proliferation of partially developed WBCs in the blood over a short period of time
What causes Acute Leukaemia?
Mutation of precursor blood cells within the bone marrow
Which types of Acute Leukaemia are there?
Acute Lymphoblastic Leukaemia
Acute Myeloid Leukaemia
What is Acute Lymphoblastic Leukaemia (ALL)?
Mutations within bone marrow give excessive proliferation of T-Lymphoblasts and B-Lymphoblasts (precursors of T-Lymphocytes and B-Lymphocytes)
What is the primary cause of ALL?
Chromosomal Translocations
Which Chromosomal Translocations are associated with development of ALL?
t(12:21)
t(9-22) - Philadelphia Translocation
What are some symptoms of ALL?
Bone Marrow Failure - Anaemia, Neutropenia, Thrombocytopenia
Bone Pain - Secondary to marrow infiltration
Splenomegaly
Hepatomegaly
Fever
What are some subtypes of ALL?
Pre-B Cell ALL
Pre-T Cell ALL - Thymus/Mediastinal mass, mainly teenagers
Mature B-Cell ALL
What are some appropriate investigations for suspected ALL?
CXR - ?Mediastinal Mass Bloods - Raised WCC, Lymphocytes Bone Marrow Biopsy Cytogenetic Testing Lymph Node Biopsy CT Scan LP - ?CNS Involvement
How may ALL be treated?
Chemotherapy - Mainstay treatment Steroids Radiotherapy Growth Factors Stem cell transplant
What are the stages of ALL treatment?
Phase 1 - Remission Induction
Phase 2 - Consolidation/Intensification Therapy
Phase 3 - Maintenance Therapy
What is Acute Myeloid Leukaemia (AML)?
Leukaemia that arises out of malignant transformation of a myeloid precursor
In which age group is AML commonly found?
Older, incidence increases with age
How is AML classified?
Using the French-American-British (FAB) Classification which is based on the appearance of Leukaemic cells on Bone Marrow Aspirate
What are some symptoms of AML?
Asymptomatic
Bone Marrow Infiltration - Anaemia, Neutropenia, Thrombocytopenia
Infection
haemorrhage
Which chromosomal translocation is associated with development of AML?
t(15;17)
What are some appropriate investigations for suspected AML?
Bloods - Raised WCC, Anaemia Bone marrow aspirate and trephine Cytochemistry Immunophenotyping Cytogenetics Molecular Biology
What are some general supportive treatment measures for AML?
Correct Anaemia
Prompt IV Abx for infections
Which chemotherapeutic agents are commonly used in AML?
Cytarabine
Idarubicin
When does Chronic Lymphocytic Leukaemia (CLL) commonly occur?
Later in life
What occurs in CLL?
Clonal expansion of Lymphocytes, mainly B-Cell
Which cell type is usually affected in CLL?
B Cell
How can CLL present?
Asymptomatic
Recurrent infections - functional leucopenia and immune failure
Anaemia - Haemolysis and marrow infiltration
Painless Lymphadenopathy
LUQ discomfort due to Splenomegaly
What are some possible clinical signs of CLL?
Anaemia
Fever secondary to infection
Lymphadenopathy
Hepatosplenomegaly
What abnormalities may be found in FBC with CLL?
Normal/Low Hb
Raised WCC with Lymphocytosis
Normal/Low Platelets
What is Lymphocytosis?
An increase in the number of Lymphocytes present in blood
How may a blood film appear in CLL?
Normal appearing Lymphocytes
What may a bone marrow aspirate demonstrate in CLL?
Heavy lymphocyte infiltration
Which CD receptors may be found on lymphocytes in CLL?
CD19+
CD5+
CD23+
How is CLL staged?
Rai-Binet staging
What percentage of confirmed CLL cases require no treatment?
30%
What are some absolute indications for treatment of CLL?
Marrow failure demonstrated by increasing anaemia and/or thrombocytopenia
Recurrent infection
Significant Splenomegaly/lymphadenopathy
Progression of disease with lymphocyte count doubling in 6m
Presence of haemolysis
Systemic Sx - Fever, Night sweats, weight loss
Which agents can be used to treat CLL?
Chlorambucil
Rituximab
Cyclophosphamide
Which transformation can CLL undergo?
Lymphomatous (Richters) Transformation
What happens in Richters transformation of CLL?
It converts to large B-Cell lymphoma
Following Richters transformation of CLL, what is the associated prognosis?
Poor, with survival often being short
What is Lymphoma?
Malignancy of the lymphatic system which can present at any site containing lympoid tissue
What are the two primary subtypes of Lymphoma?
Hodgkin’s
Non-Hodgkin’s
What is Hodgkin’s Lymphoma?
B cell lymphoma characterised by the presence of Reed-Sternberg cells
What are Reed-Sternberg cells?
Derrivations of abnormal B cells
What are some syb-types of Hodgkin’s Lymphoma?
Classical Hodgkin’s Lymphoma
Nodular Lymphocyte Predominant Hodgkin’s Lymphoma
What are some symptoms of Hodgkin’s Lymphoma?
Painless Cervical Lymphadenopathy Pain following consumption of alcohol Hepatomegaly Splenomegaly B Symptoms
What are B symptoms?
Fever
Weight loss
Pruritus
Drenching night sweats
What may investigations of Hodgkin’s Lymphoma demonstrate?
Anaemia - Normochromic, normocytic, autoimmune haemolytic anaemia Leucocytosis Raised ESR Raised LDH Abnormal LFTs
How is Hodgkin’s Lymphoma staged?
Cotswold modification of Ann-Arbor staging
Can Hodgkin’s Lymphoma be cured?
Yes, cure is possible and likely if in early stages
What treatment can be given to early stage Hodgkin’s Lymphoma?
Radiotherapy
What treatment can be given to advanced Hodgkin’s Lymphoma?
Adrimycin
Bleomycin
Vinblastine
Dacarbazine
What is Non-Hodgkin Lymphoma?
Malignant clonal expansion of Lymphocytes
Which lymphocytes are usually affected in Non-Hodgkin Lymphoma?
B Lymphocytes - 80%
T Lymphocytes - 20%
What are some risk factors for developing Non-Hodgkin Lymphoma?
Abnormal Response to Viral Infection Bacterial Infection Radiation Drugs - Phenytoin Autoimmune - Sjogrens Immunosuppression
Which virus is associated with the development of Burkitt’s Lymphoma?
Epstein-Barr Virus
Which infection is associated with the development of Gastric Lymphoma?
Chronic H.Pylori
What are some symptoms of Non-Hodgkin Lymphoma?
Widely disseminated lymphadenopathy
Splenomegaly
Hepatomegaly
Extra-nodal disease is common
What may be demonstrated biochemically in NHL?
Anaemia/Pancytopenia due to marrow failure
Peripheral blood lymphocytosis
Paraproteinaemia/Hypogammaglobulinaemia
Raised LDH
Which radiological investigations are used for investigation of suspected NHL?
XR
CT
PETCT
What is high grade NHL?
More aggressive, cure is possible
What is low-grade NHL?
More indolent, treatable but not curable
What are some examples of high grade NHL?
Diffuse Large B Cell Lymphoma
Burkitt Lymphoma
What are some examples of low grade NHL?
Small lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Follicular Lymphoma Marginal Cell Lymphoma Mantle Cell Lymphoma
What are some potential treatment options for NHL?
Excision Watch and Wait Chemotherapy Radiotherapy Monoclonal Antibody therapy Small Molecules/Targeted Therapy
What is Chronic Myeloid Leukaemia (CML)?
Myeloproliferative Neoplasm, nearly exclusively in adults with a peak incidence of 40-60y
Which mutation is found in 95% of CML cases?
Philadelphia Chromosome - t(9;22)
What can CML transform into?
Acute leukaemia or myelofibrosis due to a blast crisis transformation
What are some presenting symptoms of CML?
Asymptomatic Symptomatic Anaemia Abdominal Discomfort due to Splenomegaly B Symptoms Headaches Bruising Bleeding
What are some clinical signs suggestive of CML?
Pallor Massive splenomegaly Lymphadenopathy if blast crisis Extramedullary soft tissue leukaemic deposits - Chloroma Retinal Haemorrhage
What is a Chloroma?
Extramedullary soft tissue leukaemic deposits
What may bloods show in CML?
Low or normal HB
Raised WCC
Normal/Abnormal platelet count
What may a blood film demonstrate in CML?
Neutrophilia with Myeloid Precursors
What may a Bone Marrow aspirate demonstrate in CML?
Increased cellularity, increased myeloid precursors
Cytogenetic reveal 9;22 translocation
Which agent is used to manage CML?
Imantinib - Tyrosine Kinase inhibitor
How does Imantinib help to manage CML?
Suppresses activity of the fusion protein produced by the Philadelphia Translocation
What are some side-effects of Imantinib?
Nausea
Headaches
Rash
Cytopenia
How should an acute transformation of CML be managed?
Chemotherapy, then stem cell transplant for remission induction
If Imantinib is ineffective in managing CML, how should this be managed?
Allogeneic Stem Cell Transplant