Myeloma, Lymphoma & acute Leukaemia Flashcards
What are immunoglobulins?
-glycoproteins producedby plasma cells in response to an immunogen
What is myeloma?
-Incurable malignant disorder of clonal plasma cells
What is the diagnostic criteria for myeloma?
-Clonal plasma cells >10%
-Extramedullary plasmacytoma
AND
CRAB features, MDEs
How is myeloma linked to the kidneys?
- Renal insufficiency or impairment despite therapy
- Acute kidney injury & myeloma = medical emergency
Describe amyloidosis
- Amyloid light chain amyloidosis
- light chain fragments misfold and self-aggregate to form beta pleated fibrils
What is follicular lymphoma?
- Neoplastic disorder of lymphoid tissue
- Type of non-hodgkin lymphoma characterised by slow enlarging lymph nodes
- Male & females affected equally
- Incidence rises with age
In terms of genetics how does follicular lymphoma occur?
- Acquired chromosomal translocation
- Brings bcl2 proto-oncogene under influence of the immunoglobulin heavy chain gene
- Leads to inhibiting apoptosis
How does acute leukaemia occur?
- Somatic mutation in a single cell within a population of early progenitor cells
- De novo mutation
- Terminal event of pre-existing blood disorder
- Accum of early myeloid or lymphoid precursors in bone marrow, blood or tissue
What are the clinical features of AL?
- Features of bone marrow failure: anaemia, infections, easy bruising & haemorrhage
- Organ infiltration: spleen, liver, meninges, skin, testes
How is AL diagnosesd?
- Morphology (FAB, WHO)
- Cytochemistry
- Immunological markers (monoclonal antibodies & FACS)
- Cytogenetics/FISH (indicate subtype)
- Molecular techniques(PCR)
Name the chromosomal abnormalities in ALL and their prognosis
- High hyperdiploidy=favourable
- Hyperdiploidy & pseudodiploidy=intermediate
- Hypodiploidy=poor
- Structural abnormalities=intermediate-very poor
What molecular abnormalities can be seen in AL?
-Chromosomal translocation cause molecular changes important in aetiology. Philadelphia chromosome= t(9;22)
Give the molecular pathology of AML
- Abnormal cell proliferation= Ras & FLT3 mutations (bad)
- Block in differentiation= MLL translocation
- Tumour suppression= NPM1 (good)
What factors in ALL lead to a poor prognosis?
- Increasing age
- High WCC
- Male
- Poor response to treatment
- T-ALL & null-ALL
- Certain cytogenetic abnormalities
What is the treatment for ALL &/ AML?
AML= obtain remission, then combination chemo, consider bone marrow transplant ALL= All patients receive chemo, prophylaxis of meningeal leukaemia w/intrathecal methotrexate & cranial irradiation, bone marrow transplant in bad patients
What are complications of therapy for AL?
- All patients with intense chemo will become neutropenic
- Neutropenic Sepsis: Danger of g+ve/-ve infection-broad spectrum antibiotics
- Neutropenic fever: pyrexia in presence of very low neutrophil count
What are common causes of lymphadenopathy?
- Infection
- Autoimmune
- Malignancy
What are clinical features of non/hodgkin lymphoma?
- swelling in neck,arm,groin
- abdo pain when drinking
- heavy sweating
- weight loss
How can you distinguish between multiple myeloma, MGUS and benign polyclonal hypergammaglobulinemia?
- MM= cancer of plasma cells
- MGUS=benign abnormal protein in the blood (by plasma)
- BPH=elevated levels of gamma globulin benign immunoproliferative disorder
What are the clinical, biochemical & haematological features of multiple myeloma?
- C=bone pain, pathological fractures, weakness, hypercalcaemia
- B=abnormal total serum protein, albumin & total globulin conc
- H=osteolytic lesions, normacytic anaemia
What are the lab results for acute leukaemia
- low Hb
- WBC raised usually
- bone marrow aspirate =inc celluarity, red erythropoiesis & megakaryocytes
- acute lymphoblastic leukaemia has tendency to involve CSF
