the leukaemias - far too many cells; far too many vowels - toby m robins
TRANSCRIPT
Put that all together and you get
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphoblastic leukaemia
Chronic myeloid leukaemia
For each, we will briefly cover• Definition• Epidemiology• Aetiology• Pathogenesis• Clinical features• Investigations• Management • Prognosis
Meyloid blast cells explained
Pluripotent stem cells then divide and differentiate
either into myeloid stem cells or lymphoid stem cells
M L
Myeloid blast cells explained
Lymphoid stem cells make lymphocytes
Myeloid stem cells make all the other blood cells
There’s more than ONE kind of AML
• Morphologically, there are seven and a half:– M1 = undifferentiated blast cells– M2 = myeloblastic– M3 = promyelocytic– M4 = myelomonocytic– M4eo = myelomonocytic with dysplastic eosinophils– M5 = monocytic– M6 = erythroleukaemia– M7 = megakaryoblastic leukaemia
Aetiology
• All implicated have been– Heredity– Radiation– Mutagenic drugs– Chemical & other occupational exposures– secondary to previous chronic leukaemia or
myelodysplasia
Clinical features
• Symptoms and signs are a result of 3 things:– 1. Marrow failure– 2. Leukaemic infiltration of tissues– 3. Consitutional upset
Symptoms relating to marrow failure
• Infection• Bleeding or easy bruising• symptoms of anaemia - shortness of breath, etc
Symptoms relating to leukaemic infiltration
• Symptoms of a mass lesion (rarer, since leukaemias by definition tend not to form masses) – bone– breast, uterus, ovary– cranial or spinal dura– GI tract– lung or mediastinum– prostate
Symptoms relating to constitutional upset
• Malaise• Fatigue• Weakness• Fever or sweats• Anorexia or weight loss• Non-specific cough
Signs relating to marrow failure
• Evidence of infection• Signs of anaemia• Purpura or signs of bruising/bleeding
– including retinal haemorrhages
Signs relating to leukaemic infiltration
• Hepatosplenomegaly• Lymphadenopathy• Sternal tenderness• Thymic mass• Gingival hypertrophy
Investigations
• FBC• Blood film• U&Es• LFTs• coagulation (especially for the DIC of M3)• Bone marrow examination• cell markers and molecular studies (eg of marrow
cells)
Cell markers, molecular studies
• Flow cytometry (immunophenotyping) may aid in morphological (ie appearance-based) diagnosis and may add further prognostic information
• Karyotyping, FISH, and PCR may confirm diagnosis (eg acute promyelocytic leukamia; =M3), + may add information not otherwise obtainable
Chemotherapy
• Divided into 3 phases– 1. Remission induction– 2. Remission consolidation– 3. Remission maintenance
1. Chemotherapy for remission induction
• Complete remission (CR)– full recovery of haematopoiesis, with– blasts accounting for < 5% of bone marrow cells
• Involves mainly– anthracyclines– cytosine arabinoside
Why have they chosen these drugs?
• Anthracyclines– because AML is like cycling a “myel” and a half with
anthrax
• Cytosine arabinoside – think “sight-o-seen arabocide” – because some (ignorant,misinformed,prejudiced)
people because think an Arab that comes within a “myel” radius should be shot on sight
– sorry, Tarik, no offence :)
2. Chemotherapy for remission consolidation
• Involves similar chemotherapy to that of remission induction
3. Chemotherapy for remission maintenance
• Treatment is continued for 2 years in ALL, but for a much shorter time in AML
Bone marrow transplant (BMT)
• Suitable marrow may be– allogeneic (from histocompatible siblings or
unrelated donors)– syngeneic (from an identical twin)– autologous
BMT continued
• Used increasingly as a form of consolidation• Use depends on the pt’s age
– the elderly develop more complications
BMT continued
• Marrow is infused intravenously to “rescue” the pt from otherwise supralethal chemoradiotherapy
• Enables destruction of (almost) all leukaemic cells and the entire immune system with eg cyclophosphamide plus total body irradiation
Why use cyclophosphamide?
• ‘cause you midas well make phossels out of all those nasty leukaemia cells in one foul swoop (cycle)
A FOUL SWOOP
BMT continued
• To reduce graft vs host effect– cyclosporin +/-– methotrexate
• Complications– graft vs host disease– infections (commonly CMV)– veno-occlusive disease– relapse of leukaemia
Supportive treatment
• Blood transfusion for anaemia• Platelet transfusion for thrombocytopenic
bleeding• Prompt antibiotic treatment, and prevention,
of infections• Hygeine
Prognosis
• 70% achieve complete remission lasting (on average) 12 months
• Long-term survival (~ 50%)