Leukaemia Flashcards
(34 cards)
Leukaemia VS Lymphoma
- Leukaemia = term to describe the widesprea dinvolvement of the bone marrow accompanied with a large number of cancer cells in the peripheral blood
- Lymphoma = Proliferation of lymphoid cells arising as sicrete masses
Haemopoiesis
Classifications of WBC neoplasms
Acute VS Chronic leukaemia
- Accordign to WHO classification, blasts should be >20% in bone marrow for diagnosis of acute leukamia.
- So bone marrow biopsy is the investigation of choice for diganosing leukaemia.
- The FAB (French-americal-british classifciation) diagnostic criteria for aucte leukaemia is the presence of >30% blasts in the bone marrow (Normally <5%) and increased number of cells in the blood
- Acute leukaemias have a high rate of proiferation without differentiation and their clinical course is rapid
- Chronic leukaemias have a low rate of proliferation of tumour cells with good differentiation and their clincia course is slow.
WHO classification of the lymphoid neoplasms
What is the commonest leukamia seen in childhood with a slight predilection for males?
Acute Lympblastic Leukaemia (ALL)
Etiological agents for Acute Lymphblastic leukaemia (ALL)
- Exposure to ionising radiators as X-rays
- Chemical like benzene
- Genetic disorders like Down Syndrome
- Atazia telangiectasia
- Acquire disorders liek paroxysmal nocturnal haemoglobinuria and aplastic anaemia
WHat are the clinical Features of Acute lymphoblastic Leukaemia (ALL)
- Characterised by sudden onset of symptoms that arise due to replacement of the normal bone marrow cells with blast cells, thereby causing features/symptoms due to decreased number of RBC, WBC and platelets (anemia, infections, increased bleeding tendency respectively).
- The leukaemic cells also infiltrate the organs of the body like spleen, liver and lymph nodes cuasing splenomegaly, hepatomegaly and lymphaedonpathy
The immunological classification of Acute lymphoblastic Leukaemia
- ALL can be precursor B-cell or T-cell type
- In the pre-T-cell type, there is presence of mediastinal mass ue to thymus invovlement which can compress either the vessels or airway in the region.
Acute Lymphoblastic leukaemia (ALL) features in bone marrow
- Bone marrow expansion is repsonsible for bone pain and tenderness (usually sternal tenderness) in these patients
- Testicular invovlement and CNS features like headache, vomiting and nerve palsies are also seen in these patients.
- Aleukemic leukaemia is diagnosed by the presence of >20% blasts in the bone marrow
Investigations and Blood Findings in Acute Lymphoblastic leukaemia (ALL)
Blood:
- markedly elevated WBC count
- Uncommonly, some patients may show pancytopenia with few or no blast cells in peripheral blood which is aleukemia leukaemia
- Diagnosis made by presence of >20% blasts in the bone marrow
- Blast cells with Periodic Acid Schiff (PAS) positively are seen
- There is presence of anaemia, neutropenia and thrombocytopenia
Bone marrow: Hypercellular with blast cells >20% of the marrow cells
Biochemical investiagtions:
- Elevated serum uric acif and phosphate levels
- Hypocalcaemia (because of hyperphosphatemia)
- Serum LDH is also increased (due to increased turnover of the cancer cells)
Commonest cytogenic abnormality in ALL is hyperdiploidy.
Apart from CML, philadelphia chromosome is also seen in ALL and is associared with wors eprognosis.
Genetic Associations of ALL
- T cell ALL = associated with gain of funciton mutation in NOTCH1 gene (normally required for T celld evelopment)
- B cell ALL = associated with loss of function mutation in PAX5, E2A. EBF or balanced t(12;21) affecting TEL and AML1 genes (nromally required for B cell development)
Treatment of choice for ALL is allogenic bone marrow transplantation and cancer drug regime used for induction is VAPD (vincristine + asparaginase + prednisolone + daunoribicin) with intrathecal methotrexate.
What leukaemia affects adults most commonly between 15-39years
- Acute Myelogenous Leukaemia
Etiolgoical agents for Acute Myelogenous Leukaemia (AML)
- Exposure to ionising radiations like X-rays
- Chemicals like benzene
- Seocndary to myelodysplastic syndrome
- Drugs like anti-cancer drugs
- Genetic disorders like Downs syndrome and Fanconi’s anaemia
Define the characterists of the predominant cell in Acute Myelogenous Leukaemia (AML)
- Myeloblast is the predominant cell
- Fine nuclear chromatin
- 3-5 nucleoli
- High N:C ratio
- Presence of Auer rods (these are abdnorla aurophilic granules)
- Staining positively with Sudan black B, myeloperoxidase (MP) and Non Specific Esterase (NSE)
FAB (French - American-British) system for classifiying Acute myelogenous Leukaemia
FAB system divides AML into 8subtyes, M0 through to M7, based on the type of cell from which the leukaemia develops and its degree of maturity. This is done by examining the appearance of the malignant cells under light mciroscopy.
WHO classification for Acute Myelogenous Leukaemia (AML)
Attempts to be more clincially useful than FAB and to produce more meaningful prognostic information. The subtypes are:
- AML with characteristic genetic abnormlaities
- AML with multi-lineage dysplasia
- AML with myelodyslastic syndromes (MDS), therapy related
- AML not otherwise categorised
- Acute leukaemias of ambiuous lineage.
Clinical features of Acute Myelogenous Leukaemia (AML)
- Similar to ALL
- Fatigue due to anaemia
- Bleeding and infections in oral cavty, lungs, etc
- Bleeding diathests due to DIC which resilts from release of thromboplastic substances in the granules (most common with M3 AML)
- Infiltration of cells into the organs is relatively less common compared to ALL resulting in only mild hepatosplenomegaly and lymphadenopathy
- Gum hypertrophy and infiltration of the skin (leukemia cutis) is common particularly with M5 AML
- Less frequently, patients may present with localised massses in absence of marrow or peripheral blood involvement called myeloblastoma, granulocytic sarcoma or chloroma (turn green in presence of dilute acid due to presence of MP).
Positive markers of granulocytic sarcoma (type of AML) and symptoms
Lysozyme, CD43, CD45, CD117, MPO
These manifest as proptosis (due to orbital movement) most commonly or may present as bone or periosteal masses.
- Fever
- Repeated infections
- Fatigue
- Pal skin
- Difficult in breathing
- Pain in the bones
- Tendency for bruising and unusal bleeding
- Bleeding from nose or gums
Blood Findings in Acute Myelogenous leukaemia
Blood:
- Markedly elevated WBC count
- Findings are similar to that in ALL except that the blast cells show positivity with MPO, NSE or Sudan black
- There is presence of anaemia, neutropenia and thrombocytopenia
Bone marrow: hypercellular with blast cells>20% of the marrow cells.
Biochemical investiagtions:
- Elevated serum uric acid and phosphate levels accompanied by hypocalcemia (because of hyperphosphatemia)
- Serum Muramidase levels is also increased in M4 and M5 AML
- The fibrin degredation products (FDPs) are levated in M3 AML due to DIC
Prognostic factors in AML
Leukemoid Reaction -what is this
Leukemoid reaction = presence of elevated leucocyte count (>50,000 cells/ml) in the peripheral blood resmebling leukaemia in an individual who actually does not have leukaemia
Differentiated by leukaemia by:
- Immature cells/blasts <5%
- T leukocyte alkaline phosphatase (LAP) score
- Dohle bodies + in neutrophils
- Toxic granulations and in WBC
- Less hepatosplenomegaly
- Less lymphadenopathy
- Less haemorrhage
Diagnostic approach to leukaemias
Myelodysplastic Syndromes (MDS)
- Myelodysplastic syndromes = clonal stem cell disorder resulting in ineffective haematopoiesis and increased risk of development into AML
- The bone marrow is replaced with multipotent stem cells which can differentiate but in an unorganised and infecctive manner only
- It has been linked to the exposure to radiation, benzene, alkylating agents and some chromosomal abnormalities like monosomy 5 and 7, deletion of 5q and 7q, trisomy 8 and deletion of 20q.
- Classification:
- Primary MDS - develops slowly usually after 50years of age
- Secondary or Therapy related MDS (t-MDS) = usually 2-8years after toxic drug or radiation exposure (secondary MDS gets transformed to AML most frequenlty and has poorer prognosis)
