What is myeloid and lymphoid precursor?
Myeloid: platelets, RBC, macrophages, basophils/eosinophil/neutrophils
Lymphoid: T and B cells
What is the difference between acute and chronic leukemia?
acute: cells dont mature and remain in ‘blast’ form: monoblasts/myeloblasts…
chronic: similar appearance to mature cells but lack their functionality: monocytes, progranulocytes …
What is the symptoms for leukemia?
Anaemia - Fatigue - Dyspnoea - Palpitations Thrombocytopenia - Easy bruising - Mucosal bleeding Leukopenia - Recurrent infection Hepatomegaly, abdominal fullness Blast cells infiltration of bone marrow - Pain and tenderness in bones Lymphadenopathy - More common in CLL and ALL as lymphoblasts settle more common in liver, spleen and lymph nodes - Mild and localised pain in lymph nodes Swelling of gum - Monocytic infiltration in AML
What is AML?
- myeloidblasts
- Common in older adults (average 65 yo)
- Chromosomal translocation of 15 and 17
associate with Down Syndrome (chromosome 21 trisomy) - Risk factor
Exposure to radiation
Alkylating chemotherapy
What is ALL?
Lymphoblasts common in children - Risk factor Exposure to radiation Alkylating chemotherapy
- CNS/meninges involvement
- Mediastinal involvement
- Testicular involvement/enlargement
What is CML?
- Caused by chromosomal translocation (Philadelphia chromosome 22)
Chromosome 9 long arm and chromosome 22 long arm - BCR ABL gene
- granulocytes
- Retinal haemorrhage due to leukostaisis
- GOUT due to purine breakdown from inc white cells
What are physical exams of leukemia?
- Pallor
- Fever due to infection
- Petechiae, purpura
- Bruising
- Lymphadenopathy
- Hepatosplenomegaly
- Meningeal leukemia infiltration of lymphocytes in meninges (ALL)
Neck stiffness, purple rashes
Brudzinski sign: hip and knee flex when neck is flexed
Kernig sign: severe stiffness of hamstrings cause inability to straighten leg when hip is flexed at 90 degrees
What are some investigations for leukemia?
- CBE
Dec Hb/platelet, inc WBC
EUC: inc uric acid, potassium and nitrates in cell lysis - Peripheral blood smear
Myeloblasts: AML
Lymphoblasts: ALL - Coagulation profile: do it for bleeding or petechiae
- Bone marrow biopsy
Inc blast cells to > 20% (normal is 1-2%)
Inc lymphoblasts/myeloblasts - cytogenetics: philadelphia chromosomes
Differentiate AML and ALL
- stained smear: myeloblasts are larger and finer chromatin, auer rods
- immunophentotyping: express different CD receptors
What are some overall treatment options for leukemia?
Chemotherapy Stem cell transplant Steroids TKI for CML Complication management
What is involved in leukemia chemo?
- Cause apoptosis by initiating cellular stress pathways such as damaging DNA
- Cell cycle will not continue apoptosis caused by cellular checkpoints
- Each dose kills a % of cells so repeating cycle eventually reduce tumour to 0
cytotoxic anti-neoplastic medication
- alkylating, antimetabolites, antimicrotubular, topoisomerase inhibitors, allopurinol
side effect of chemo
- nausea/vomiting, hair loss, easy bruising/bleeding
drugs treating nausea/vomiting
- ondansetron, dexamethasone, sedating anti-histamine, SP antagonists
What is involved in leukemia stem cell transplantation?
- Transplantation of multipotent stem cells
- Sources
Bone marrow: pelvis, under general anaesthesia
Peripheral blood stem cells: most common, donor’s blood pass through machine that removes WBC and RBC are returned to donor blood stem cells lead to quicker recovery of marrow function following myeloblative chemotherapy
Umbilical cord blood
What is involved in leukemia steroids?
dexamethasone Short term adverse effect - Immunosuppression - Mood changes (euphoria) - Mood swings in between short term and long term - Insomnia - High blood glucose level
Long term adverse effect
- Significant immunosuppression
- Mood changes (depression)
- Osteoporosis
- Weight gain
What is tyrosine kinase inhibitor in CML?
It targets BCR-ABL gene and inhibits the activity of tyrosine kinase
- First generation: imatinib
Well-tolerated and 87% of patients achieve complete haematological response
- Second generation: dasatinib, nilotinib
If patient is intolerant or unresponsive to first line
PCR for BRC-ABL is used for monitoring response to therapy
It is NOT a cure.
Failure of marrow failure
- Iron/B12/folate deficiency
- Marrow infiltration by lymphoma or non-haematological malignancy
- Aplastic anaemia – viral, toxic, autoimmune
- Chronic inflammatory disease – anaemia
- Lack of simulating factors due to liver/renal disease EPO, TPO
What are some causes of splenomegaly
Causes of splenomegaly (CHICAGO)
- Cancer
- Haematological (sickle cell anaemia, leukemia, lymphoma)
- Infection/inflammation (Hep, HIV, TB, malaria)
- Congestion (portal hypertension)
- Autoimmune (Rheumatoid arthritis, SLE)
- Glycogen storage disorders
- Other
