Haematology Malignancies 1 Flashcards
Describe haematopoiesis
Multipotential hematopoietic stem cell
Either go into
Common myeloid progenitor = myeloblast = monocyte = macrophage + dendritic cell
Common lymphoid progenitor = NK cell or small lymphocyte = T or B cell = plasma cell
What are the different classifications of haematological malignancies?
Acute myeloid leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)
Chronic myeloid leukaemia (CML)
Chronic lymphocytic leukaemia (CLL)
Myeloma
Describe acute leukaemias
Aggressive
Rapid growing
More common in children
Describe chronic leukaemia
Slow growing = NOT symptomatic at first
More common in adults
Describe the development of leukaemia in bloodstream
Stage 1 = normal
Stage 2 = symptoms = spilling into blood from bone marrow = blasts appear in the blood = symptoms appear
Stage 3 = diagnosis = WBC + platelets + RBC dropping = bone marrow packed with leukemic cells = decreases others
Stage 4 = worsening = more decrease in cells
Stage 5a = anaemia = no RBC/platelets = extreme tiredness + bruising = severe symptoms
Stage 5b = repeated infections = no WBC = severe symptoms
What are the symptoms associated with bone marrow failure?
Anaemia = fatigue + pallor
Thrombocytopenia = bruising/bleeding
Neutropenia = infection
Bone pain, weight loss
What are the symptoms associated with organ infiltration?
Lymphatic system = lymphadenopathy, splenomegaly
CNS involvement = confusion, seizures = sign of progression
Skin/gums = gum hypertrophy
Testicular involvement = sign of progression
Mediastinal mass = T lineage ALL
What are the diagnostic investigations?
FBC + blood film = pancytopenia (all blood cells low), raised WBCs (accumulation of poorly differentiated blast cells) + blast cells on blood film
Lactate dehydrogenase (LDH) = marker of high metabolic activity
Coagulation screen = bleeding abnormalities
Imaging = check progression of disease
Bone marrow aspiration/biopsy = main diagnostic
Immunophenotyping = type of leukaemia
Cytogenetic analysis = deem prognosis
Describe the initial management
Rapid diagnosis + access to treatment required
Emergency treatment of complications = hydration + correction of electrolyte imbalances, treatment of infection, prevention of uric acid nephropathy + correction of coagulopathy + blood product support
HLA typing = donor for bone marrow transplant = allogenic transplant = NOT 1st line except those high risk
Suppression of menses = risk associated with chemo SEs
What is the patient-centred care in haematological malignancies?
Patient needs to be informed = long term + aggressive
Co-ordination of care
Provision of information
Practical + social support = family
Fertility considerations
Nutritional support
Physiotherapy + occupational therapy
Psychological support
Describe the treatment of acute leukaemia
Induction phase = 4-6 weeks
Intensive chemo to eradicate leukemic clone + induce complete remission
Consolidation (4-12 weeks)/Intensification phase (8-12 weeks)
Further high dose of chemo to eradicate residual undetectable leukemic clone
Prolonged maintenance phase (2-3 years) (ALL not AML)
Lower dose outpatient treatment schedule to prevent relapse
Describe CNS directed therapy
Preventative intrathecal chemo = prevent relapse in the brain
Throughout all phases
Describe the supportive care
Prevention of tumour lysis syndrome = aggressive hydration + allopurinol
Prevention of febrile neutropenia = IV Abx
Prevention of CINV
Pneumocystis jiroveci pneumonia (PCP) prophylaxis = co-trimoxazole
What is tumour lysis syndrome?
Complication of treating high cell count diseases
As cells die contents leak into plasma = hyperkalaemia, hypercalcaemia, urate precipitation + renal dysfunction
Describe the poor prognostic indicators in ALL
Most common leukaemia in children
Unfavourable cytogenetics
Increasing age
Male sex
High WBC at diagnosis
Presence of CNS disease
Poor response to initial treatment = blasts present in bone marrow on day 14 + complete response not achieved at day 28
Describe asparaginase
Targeted therapy
Catalyses the hydrolysis of asparagine to aspartic acid + ammonia = rapid depletion of asparagine
But results in considerable cytotoxicity
What is asparagine?
Essential amino acid in lymphoid malignant cells = required for protein synthesis
Lymphoid malignant cells lack ability to synthesize asparagine
Describe relapse
CNS + testicular relapse has better prognosis than bone marrow relapse
Localised therapy + second full course systemic chemo
Prognosis is related to duration of remission = longer remission = better prognosis
Allogenic transplant = donor cells = need immunosuppressants = reduce rejection risk
CAR-T therapy
Describe CAR-T
Get blood with T cells from patient
Create CAR-T cells that react to cancer cells
Grow CAR-T cells in vivo
Inject CAR-T into patient
CAR-T cells attack cancer cells
