Haematology Flashcards
What is acute leukemia?
The rapid proliferation of immature blood cells (blast).
>20% blast in BM for diagnosis
Highest growth fraction
HSC is already lymphoid or myeloid committed, hence AML OR ALL
What is chronic leukemia?
Proliferation and excessive build-up of relatively mature blood cells over a longer timeframe.
Apparently mature, but not normal.
Usually lost of apoptotic mechanisms.
Define leukemogenesis.
Gene mutations in bone marrow progenitor cells underlie the malignant transformation of normal haemopoietic cells.
Outline the concept of an oncogene.
They are mutations in a pro-oncogene -required cell growth.
Oncogenes promote cell growth, uncontrollably, either by chemical messengers or signal conduction.
Expression in inappropriate cell types, activating the expression of the gene under inappropriate conditions, changing the localisation of the protein product, making the protein unresponsive to cell signaling cascade regulation etc.
Production and maintenance of malignancy.
Outline the concept of oncogenesis.
Carcinogenesis- normal cells to cancerous cells.
Cellular, genetic, and epigenetic levels
Somatic mutation- disrupts the regulated cell division and cell death in the body.
Cancer-promoting genes suppress Tumour Suppressor genes.
How does dysregulation lead to neoplasms?
Cancerous tissue proliferates and forms an abnormal growth of tissue called neoplasms.
These cells undergo metaplasia or dysplasia.
Why are malignancies referred to as clonal disorders?
That all malignant cells are descendants of one early precursor cell that underwent a malignant transformation.
Describe APL.
RARA gene (which is important for neutrophil production) translocates with PML and disrupts normal myeloid differentiation. Causes DIC due to the release of pro-coagulants.
Do a FISH testing
(15,17)
Describe the complication of Bone Marrow failure.
Systemic Anaemia- due to reduced RBC production and blood loss. More susceptible to infections and harder to fight them off. Stroke.
Thrombocytopenia- Excessive bleeding and bruising.
Neutropenia- cause severe infections that can lead to neutropenic fevers
Describe what would be seen on a full blood count, that indicates the possibility of leukemia.
WBC elevated- immune response to cancer
however the automated analyser can pick up blasts as WBC. WBC can also stay low- have not entered circulation as yet.
Blood films can give a hint of AML or ALL
Normocytic anaemia
thrombocytopenia
The Diagnosis is confirmed by a bone marrow biopsy.
Describe the morphology of AML.
Large blasts
Primitive nuclei
Cytoplasmic granules
Auer rods
from a HSC that is myeloid committed
Describe the morphology of ALL.
Scanty cytoplasm
Primitive nuclei
No cytoplasm granules
No Auer rods
From HSC that is lymphoid committed
What is the importance of a bone marrow biopsy?
To confirm an acute leukemia diagnosis.
To assess the blast morphology.
Used for other special tests to subclassify
Explain the rationale behind immunophenotyping.
The best method to use when sub-classifying acute leukemia.
It analyses cellular Antigens, surface, cytoplasm, etc.
Determines lineage
Describe leukostasis.
Hyperviscosity due increase in WBC
AML and CML
Decreased tissue perfusion, can lead to pulmonary and neurological symptoms.
Do not give RBC.
What are the side effects of chemotherapy?
Short-term effects include:
Bone marrow suppression and pancytopenia.
Risk for severe infection due to neutropenia and concurrent steroid use.
Nausea and vomiting (very common)
Diarrhoea
Tumour lysis syndrome
Mouth ulcers
Teratogenicity
Autonomic neuropathy (paraesthesia in hands and feet)
Differentiation syndrome in APL
Reactivation of latent viral hepatitis.
Long-term side effects include:
Risk of secondary malignancies (solid tumours or haematological malignancies, especially if patient is treated with both chemotherapy and radiotherapy.
Reduced fertility.
Cardiac failure (some drugs).
Osteopenia/osteoporosis.
Hypothyroidism
Growth restriction in children
Describe the clinical representation of non-Hodgkins lymphoma.
Malignant cells are highly mobile with early dissemination to other organs such as the bone marrow, liver, skin, GIT, lungs, or CNS and the NHLs often have multicentric lymph node involvement on presentation.
What are B symptoms composed of and what is their significance?
the triad of the unexplained temperature of >38°C, drenching night sweats and >10% weight loss in the previous 6 months.
associated with increased grade and widespread disease and a poor correlation with survival has been described
What is the pathogenesis of Burkitts Lymphoma?
Presence of translocated c-MYC proto-oncogene (on chromosome 8) to immunoglobulin heavy chain (chr 14) or light chain (kappa on chr 2, lambda on chr 22).
High incidence of EBV infection, particularly in immunosuppressed patients.
What are the three clinical presentations of Burkitt’s lymphoma?
ENDEMIC: the classic east African tumour of the jaw/maxilla
SPORADIC: found mainly in children and young adults, (can spread extranodal)
IMMUNODEFICIENCY ASSOCIATED: HIV, other immune deficiencies/drugs. (can spread extranodal)
Describe the features of T-cell Lymphomas.
Are usually widely disseminated and patients present with B symptoms and increased LDH levels.
Haemophagocytosis may be seen in the bone
marrow.
What is chronic lymphocytic leukaemia?(CLL)
A lymphoproliferative disorder and the malignant cells are typically small mature B-lineage lymphocytes that also express a single T- cell marker, CD 5.
What are the symptoms of CLL?
Infection- Neutropenia
Cytopenia
lymphadenopathy
splenomegaly
anaemia (auto-immune haemolytic)
Bone marrow infiltrates- interstitial, nodular or diffuse.
Describe the disease that CLL can transform into?
Transform to a high-grade B-cell lymphoma (Richters transformation)
Classic Hodgkin lymphoma
Define plasma cell neoplasms
A group of neoplastic disorders characterised by the presence of a clone of malignant plasma cells in the bone marrow (the size of the clone varies). Clonal plasma cells produce a monoclonal protein/IgG (secretes M Proteins), the so-called paraprotein, which can consist of complete immunoglobulins.
What are the characteristics of MGUS (monoclonal gammopathy of uncertain significance)
A serum monoclonal protein of <3g/dl
Bone marrow plasma cell burden of <10%
No other evidence of a proliferative plasma cell disorder.
What are the characteristics of Plasma Myeloma?
Serum Monoclonal protein of 3g/dl or more
Bone marrow plasma cell burden of 10% or more
The additional presence of end-organ damage: anaemia, bone disease, renal failure, and hypercalcaemia
How do you diagnose symptomatic myeloma?
C-HyperCalcaemia
R-Renal insufficiency Bence Jones protein deposition in renal tubules, recurrent
pyelonephritis and less commonly amyloid deposition
A-Anaemia bone marrow infiltration, anaemia of chronic disease, renal failure
B-Bone lesions: lytic lesions / pathological fractures à pain, osteoporosis
What are other symptoms associated with plasma myeloma?
Recurrent infections abnormal antibody production, neutropenia due to bone
marrow infiltration
Bleeding paraprotein interference with platelets/coagulation factors
Amyloidosis-deposition of amyloid fibrils, formed from denatured light chains
Hyperviscosity hemorrhage, loss of vision, CNS sx, neuropathies, cardiac failure
Explain the effects of the Philadelphia chromosome.
Uncontrolled differentiation
Uncontrolled proliferation
Anti-apoptotic properties
Decreased adhesion to the
bone marrow spills into
blood with very high white
cell count
Genomic instability thus can
progress to acute leukaemia.
Define Chronic Myeloid Leukaemia, CML.
Myeloproliferative neoplasm in which the granulocytes are the major
proliferative component
Describe the phases of CML
Initial chronic stable phase
-Increase granulocytes still able to differentiate into mature Neu, baso, eosino.
-Blasts in peripheral blood or bone marrow <10% and basophils <20%
-Diagnoses
Chronic phase with high-risk features
-Increasing blast count by 10 to 19%
-Increasing basophil count ≥20%
-Platelet count either very low or very high
-Increasing spleen size
Blast phase
-Acute leukaemia- >20%
What causes morbidity and mortality in Philadelphia negative patients?
Arterial and venous thrombosis
Define Essential Thrombocythaemia (ET).
Myeloproliferative neoplasm in which the megakaryocytes are the major
proliferative component.
Fundamental pathological findings = sustained platelet count > 450 x 109 /L and proliferation of mainly enlarged, hyperlobated megakaryocytes in the bone marrow
What are the causes of reactive thrombocytosis?
(Mnemonic: ‘If bleeding or haemolysis, I should remember iron deficiency, cancer and the spleen’)
Infection/inflammation
Bleeding or Haemolysis
Inherited
Surgery
Rebound thrombocytosis (recovery from chemotherapy etc.)
Iron deficiency
Drugs such as steroid therapy
Cancer (haemopoietic and non-haemopoietic)
Splenectomy
Define Polycythaemia vera (PV).
Myeloproliferative neoplasm characterised by the increase in red blood cell production independent of the mechanisms that normally regulate erythropoiesis
What is the clinical presentation of PV?
Thromboses
Hyperviscosity
Megalies
Define Primary myelofibrosis (PMF).
Myeloproliferative neoplasm characterised by the proliferation of predominantly abnormal megakaryocytes in the BM
and progressive fibrosis
What are the phases of PMF?
Pre-fibrotic phase:
-Hypercellular marrow with increased neutrophils and proliferation of
markedly abnormal megakaryocytes
-minimal fibrosis (< grade 1)
-Anaemia
-+/- splenomegaly (might not be palpable in the very early stages)
Overt fibrotic phase:
-Increased reticulin +/- collagen fibrosis (grade 2-3) - progressively displaces normal haemopoiesis
-Anaemia
-Massive splenomegaly
-Peripheral blood film:
– Increase in red cell teardrop shapes and poikilocytes
– Leucoerythroblastic blood picture = granulocyte precursors + nucleated red cells
What is the CML Triad?
Increase granulocyte count in peripheral blood and bone marrow.
Splenomegaly
Philadelphia chromosome.
What is the treatment for CML and how does it work?
Imatinib
