Haem Malignancies Flashcards
(35 cards)
What do myeloid precusor cells give rise to?
- Granulocytes:
- basophils
- neutrophils
- eosinophils
- mast cells
- monocytes –> macrophages - RBCs
- Megakaryocytes –> platelets bud off
What do common lymphoid precusors give rise to?
Lymphocytes:
- B cells
- T cells
- NK cells
*dendritic cells can arise from either this pathway or as part of granulocytes (from myeloid precursor)
Bone marrow samples - types and preferred sites
- bone marrow aspirate: takes a little of the liquid found in the bone marrow space
- bone marrow biopsy (trephine): takes a small sample of harder bone marrow tissue.
Preferred sites:
- iliac crest (anterior or posterior)
- tibia
- sternum
Acute leukaemia - definition
Neoplastic disease of immature blood cells (blasts) in the bone marrow. Can arise from myeloid or lymphoid lineage
Acute leukaemia - general features
- Tiredness, infection, bruising/bleeding
- High white cell count
- Low haemoglobin (anaemia)
- Low platelet count (thrombocytopenia)
- Low neutrophil count (neutropenia)
- High WCC due to infections
Acute leukaemia and infections
- Low neutrophil count (neutropenia) –> increased risk of infection (febrile neutropenia)
- chemotherapy –> mucositis (risk of mouth infections)
- Indwelling central venous line –> line infection (staph aureus)
Acute myeloid leukaemia (AML) - features
- mainly >65 years
- RF: Radiation, previous chemotherapy, congenital syndromes, previous myelodysplastic syndrome
- auer rods on blood smear
- Tiredness, infection, bleeding, ecchymoses or petechiae
- splenomegaly, bone pain
What are auer rods?
Auer rods are cytoplasmic inclusions which result from an abnormal fusion of the primary granules.
- seen in acute myeloid leukaemia
- found on blood smear
Au = gold; granules of gold –> ganulocytes (myeloid)
Acute lymphoblastic leukaemia (ALL) - features
- 30% of childhood cancer
- 20% of adult acute leukaemia
- RF: Radiation, Downs syndrome, M>F
- +ve philadelphia chr common in adults
Symptoms and signs
- Tired, anaemic, bruising, bleeding and low platelets, weight loss
- Abdominal pain, lymphadenopathy, splenomegaly, hepatomegaly, bone pain, +/- fever, testicular swelling
What is the relevance of the philadelphia chromosome?
Cytogenetic abnormality results from chromosomal translocation t(9;22)(q34;q11) on the Philadelphia chromosome, found on molecular studies in:
- Chronic myeloid leukaemia (95%) - pathognomonic
- most common cytogenic abnormality in adult ALL
AML - treatment
- 3 to 4 cycles of combination chemotherapy
e. g retinoic acid induces blast to mature to neutrophil - Haemopoietic stem-cell transplant (HSCT) for some or bone marrow transplant
ALL - treatment
- Induction (includes prednisolone/dexamethasone and vincristine) and consolidation chemotherapy (high-dose)
- HSCT or bone marrow transplant
- CNS prophylaxis throughout as can progress to/relapse in brain and spinal cord so intrathecal chemo +/- radio
- If Philadelphia positive ALL- also give Imatinib(Glivec)
- consider fluids, Abx prophylaxis, RBC transfusion etc
Acute vs Chronic leukaemia
ACUTE: no mature cells therefore low neutrophils, lymphocytes etc.
CHRONIC: mature cells affected therefore high neutrophils, lymphocytes
Chronic leukaemia - def and types
Neoplastic disease of mature white blood cells in the bone marrow
Types:
- Chronic myeloid leukaemia (CML): overlaps with myeloproliferative disorders
- Chronic lymphocytic leukaemia (CLL): overlaps with lymphomas
Chronic lymphocytic leukaemia (CLL) - features
- Majority of pts > 60 (most common type in adults)
- Slow accumulation of CLL cells in blood, bone marrow, lymph nodes, liver, spleen
- Hepatosplenomegaly and lymphadenopathy
- B symptoms: night sweats, persistent fever, weight loss, itching
- autoimmune haemolytic anaemia in 10-15%
- Can transform to high grade lymphoma (5%) (Richter’s transformation)
CLL - Dx and treatment
Diagnosed by FBC with differential (absolute lymphocytosis, can have normal or low Hb and platelets), blood smear showing smudge cells (aka smear cells), and flow cytometry
Treatment
- Observation (early stage) or Chemotherapy
- If not working or relapse, then use biological agents (Antibody therapy eg. Alemtuzumab, Rituximab)
- Last resort is allogeneic stem-cell transplantation
CLL progressing to lymphoma - presentation
similarly to CLL the lymphocyte count is high but when progession to lymphoma occurs the Hb level goes really low and the patient is anaemic
- sudden onset of B symptoms
- progressive lymphadenopathy
- high serum levels of lactate dehydrogenase
Chronic Myeloid Leukaemia
- Median age 50-60yrs old
- Philadelphia chromosome: most commonly associated with CML ( 95%)
- 20-50% asymptomatic (‘incidental’ finding on FBC)
- Splenomegaly, Bony pain
- Peripheral blood and BM demonstrates the presence of BCR-Abl fusion gene
- an increase in granulocytes at different stages of maturation +/- thrombocytosis
- can progress to acute leukaemia (‘blast crisis’)
- Mx: Imatinib or other Tyrosine kinase inhibitors; interferon-alpha; allogenic bone marrow transplant
Myeloproliferative disorders
Over-production of mature blood cells
↑ Neutrophils = chronic myeloid leukaemia (CML)
↑ Red cells = polycythaemia rubra vera (PRV)
↑ Platelets = essential thrombocytosis (ET)
↑ fibroblasts = Idiopathic myelofibrosis: results in replacement of bone marrow/other sites with collagen
Myelodysplasia (myelodysplastic syndrome - MDS)
Pre-cancerous disease of bone marrow, where the dysplastic cells may cause abnormal blood cell production (bone marrow trying to compensate)
- Consider this in patients with abnormal blood counts with no obvious explanation (e.g. macrocytic anaemia)
- Dysplastic morphology
- Almost exclusively patients over 60
- Can also progress to acute leukaemia
Myeloma - definition
Neoplastic disease of plasma cells (activated B cell - antibody producing)
Leads to increase production of antibodies (in case of myeloma known as paraprotein) - they can build up in kidney
Also there is less room for other blood cells to grow in bone marrow, so can get pancytopenia
Myeoloma - features
- Anaemia
- Pancytopenia
- Median age at diagnosis 66
- Bone problems: lytic bone lesions, pathological fractures (paraplegia), hypercalcaemia
- Monoclonal paraprotein (IgG or IgA or free light chain)
- Hyperviscosity of blood can lead to clots
- Cx: Renal Failure
Treatment
Induction with combination chemotherapy
Autologous stem-cell transplant in first remission
bone disease –> biphosphonates (Zoledronic acid), analgesia
CRABBI - calcium, renal, anaemia, bleeding, bone, infections
MM - investigations
- bloods: FBC, U+Es, calcium
- Serum or urine protein electrophoresis: raised monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins
(the proteins are immunoglobulin light chains (paraproteins) and produced by neoplastic plasma cells) - Bone marrow aspiration and trephine biopsy: confirms dx if the number of plasma cells is significantly raised
- Whole body MRI (or CT) is used to survey the skeleton for bone lesions
- A common X-ray finding is a ‘rain-drop’ skull - numerous randomly placed dark spots which occur due to bone lysis.
Lymphoma - definition and types
Neoplastic disease of mature lymphocytes in lymphoid tissues (lymph nodes, gut, tonsils, skin etc)
- commonly a solid tumour all in one place
- Hodgkin Lymphoma
- classical HL
- nodular lymphocyte predominant (NLPHL) - Non-Hodgkin Lymphoma
- B cell (low or high grade)
- T cell (systemic or cutaneous)
