Haematological malignancy Flashcards
What is the pathophysiology of ALL?
Proliferation of malignant precursor lymphoid cells in the bone marrow. Either B (most common) or T cells.
The proliferating malignant cells replace normal lines = normal suppressed = anaemia, thrombocytopenia and neutropenia.
Most common in children, 2-4 years.
What is the Philadelphia chromosome?
t(9;22) - associated w a poor prognosis
BCR gene and ABL gene swap (BCR-ABL) = increases tyrosine kinase = tells the cells to keep on proliferating = cancer, particularly in CML
What are the different groups of CF associated w ALL?
Marrow failure
Tissue infiltration
Leucostasis
What are the CF of marrow failure?
Anaemia - fatigue, SOB, angina, palor
Neutropenia - recurrent infections, sore throat, fever
Thombocytopenia - petechiae, nose bleeds, bruising
What are the CF of tissue infiltration?
Lymphadenopathy and hepatosplenomegaly - common at diagnosis
Bone pain
Mediastinal mass - could cause SVCO
Testicular enlargement
What is leucostasis?
Increased WCC in blood = thicker blood/impaired flow through small vessels: alt mental state, headache, breathlessness, visual changes
Also called meningeal syndrome - headache, N+V, blurred vision and diplopia - fundoscopy = papilloedema
What are the blood ix into ALL?
FBC - anaemia, thrombocytopenia, leucocytosis and neutropenia
U+E and LFTs - hypercalcaemia from paraneoplastic sydnrome, also baseline to check func before begin treatment
Coag screen and D dimer - assess for DIC
Uric acid and LDH - non specific markers of tumour burden
BBV screen ?
Blood film - blast cells
What is the imaging into ALL?
CXR - may have mediastinal mass
CT chest, AP - lymphadenopathy and organ involve, lytic lesions, enlarged thymus in T ALL
CT/MRI head - if pt sx indicate neuro involve
What is the diagnostic test in ALL?
Bone marrow aspiration and biopsy:
- Staining
- Review cell morphology
- Immumophenotyping
- Cytogenetics
- Flow cytometry
What are some additional ix into ALL?
- Blood film - blast cells
- Pleural tap
- LP - if concerned about CNS involve (but can promote spread of tumour cells into CNS)
What factors are associated w poorer prognosis in ALL?
(in adult pt):
- Increasing age
- Performance status >1
- High WCC - >30 B cell and >100 T cell
- Philadelphia chromosome
- CNS involvement
What is the classification of ALL?
Morphological
Immunological - surface markers
Cytogenic - chromosomal analysis, used for prognostic assessment
What is the supportive management of ALL and AML?
Blood <80g/l/platelet <10/l transfusion or<20 if bleed/septic
IV fluids, electrolyte replacement + allopurinol - prevent tumour lysis syndrome
Port system or Hickman line inserted
Infection prevention - prophylactic abx, anti virals and anti fungals
Anti emetics - ondansetron and they possible addition of dex, treat before N happens
Fertility treatment eg. freeze sperm/eggs
Macmillan nurse
What is the definitive management of ALL?
Chemo:
- Complex multi drug chemo, have multiple rounds and may take years
- Induce remission - vincristine, preg, L-asparaginase, daunorubicin
- Possible stem cell transplant
- CNS prophylaxis - IT/IV mtx
- Maintenance - prolonged chemo agents for 2 years eg. vincristine, dex, mtx
What is the pathophysiological of AML?
Genetic changes in myeloid precursor cells = proliferating immature cells that don’t respond to normal control mechanisms.
Results in reduced normal haemopoiesis.
What are some RF of AML?
- Myelodysplastic syndrome - blood disorders that affect haemopoiesis
- Down’s syndrome and other congenital disorders
- Radiation exposure
- Prev chemo
- Increasing age ~70 years
What are the CF of AML?
Marrow failure
Leucostasis
Tissue infiltration:
- Lymphadenopathy and hepatosplenomegaly
- Bone pain
- Gum hypertrophy
- Violaceous skin deposits
- Testicular enlargement
What are the blood ix into AML?
FBC - anaemia, thrombocytopenia, reduced reticulocyte, raised WCC
U+E - important when ruling out tumour lysis
Coag screen to rule out DIC
LDH - raised = high cell turnover
BBV screen
Blood film - Auer rods in myeloid blasts = pathognomonic
What are the other ix into AML?
- BM aspirate and trephine biopsy - >20% blast count, then cytogenetics, cytometry, immunophenotyping
- LP
What is the definitive treatment of AML?
Chemo - 5 cycles given in 1 week blocks = daunorubicin, cytarabine, given in blocks to allow blood count to recover in between, takes ~4-6 w
Marrow transplant - eradicate abnormal cells first then repopulate w donor marrow, give immunosuppression to prevent rejection, poor prognosis or relapse
What are the poor prognostic factors of AML?
> 60
20% blasts after 1st round of chemo
Poor performance status/comorbidities
Prev haematological disorders/dysplasia
Prev chemo/RT
What is chronic lymphocytic leukaemia?
Abnormal cloncal expansion of B cells that resemble mature lymphocytes = widespread lymphadenopathy and secondary immune def and cytopenias
What is the timeline of CLL?
Some pt are asymptomatic for many years
Others may get rapidly progressive disease that is symptomatic - progressive lymphadenopathy, hepatosplenomegaly
What are the CF of CLL?
Lymphadenopathy !!
Sx - weight loss, fever, anorexia, night sweats, lethargy
Signs - lymphadenopathy, hepatomegaly, splenomegaly
Features due to complications - autoimmune haemolytic anaemia (pale, SOB, fatigue), ITP (petechiae, bruise, bleed), recurrent infections
What are ix into CLL?
FBC - raised lymphocytes, low Hb then haemolysis, low neutrophils and low platelets = BM failure
Blood film - smudge cells, smear cells !!!!!! most important
Flow cytometry, immunohistochemistry, cytogenetics
LN biopsy
What are the different types of BM biopsy?
Marrow aspirate - liquid sample for cytology
Trephine biopsy - core sample
BM biopsy
What is the staging of CLL?
Binet:
Stage A <3 lymphoid sites - >10yr
Stage B >3 lymphoid sites >8yr
Stage C = anaemia and thrombocytopenia ~6.5yr
Rai staging:
Stage 0 - lymphocytosis
Stage I-II - lymphocytosis + lymphadenopathy + organomegaly
Stage III-IV - lymphocytosis + anaemia or thrombocytopenia + organomegaly + lymphadenopathy
What are some prognosis factors?
- Lymphocyte doubling time, the faster the worse the prognosis
- Genetic abnormalities = TP53, trisomy 21
- B2M
What is the management of CLL?
- Watch and wait for asymptomatic pt w/o poor prognostic factors
- Pharmacotherapy
- Allogenic stem cell transplant - chemo to destroy BM then replace w donor haemopoietic stem cells
- Supportive care
What are indications for treatment of CLL?
- BM failure
- Massive, progressive or symptomatic splenomegaly/lymphadenopathy/lymphocytosis
- Autoimmune complications not responsive to steroids eg. ITP
- Disease related sx
What pharmacotherapy things can be used for CLL?
Chemo - chlorambucil, fludarabine, bendamustine
Small molecule inhib - ibrutinib (tyrosine kinase inhib), idelalisib, venetoclax
Monoclonal ab - rituximab
Steroids in vv frail pt
What is Richter transformation?
CLL to aggressive lymphoma, ~5-8 month survival
What genetic abnormality is found in CML?
Ph chromosome
BCR-ABL blood test for disease response, should be reducing
What is chronic myeloid leukaemia?
Clonal myeloproliferative neoplasm w abnormal expansion of cells of myeloid lineage, most commonly granulocyte