|Leukaemias in General
|Acute Promyelocytic Leukaemia
|Acute Myeloblastic Leukaemia (AML)
|Acute Lymphoblastic Leukaemia (ALL)
|Chronic Lymphocytic leukaemia (CLL)
|Chronic Myeloid Leukaemia (CML)
|Hairy Cell Leukaemia
|Tretinoin (All-trans-retinoic acid (ATRA) )
|Immune(Idiopathic) Thrombocytopenic Purpura (ITP)
The bcr-abl fusion protein is the proto-oncogene from the Philadelphia chromosome found in CML. It is a potent tyrosine kinase which stimulates signal transduction and hence mitosis.
- A myeloproliferative stem cell disorder predominantly involving granulocytes
- Seen in Age range mainly of 35-75
- Cytogenetics reveal t(9:22) Philadelphia chromosome
- Forms a BCR ABL fusion gene which codes for a 210 kDa protein
- This has tyrosine kinase activity, which acts as an oncogene
- Imatinib ( tyrosine kinase inhibitor) is first-line for the treatment of the chronic phase
- 1. Chronic phase for up to 5 years which can be prolonged by Imatinib
- 2. An accelerated phase may be seen
- 3. Blast crisis to ether AML or ALL which is difficult to treat which has reduced in frequency by Imatinib. This happens after a chronic course of 2-5 years unless treated and transforms into acute leukaemia, myeloblastic or lymphoblastic as a terminal event.
- Typically seen in later middle age
- Fevers, sweats and weight loss and even priapism can be a presenting feature
- Abdominal pain - Ulcer disease (Increased Basophil cell mass release histamine)
- Massive splenomegaly or even acute abdomen due to splenic infarction
- Lymphadenopathy is not common until there is a blast crisis
- CML can rapidly develop into AML or Myelofibrosis
- May progress over the years from Chronic ? Accelerated ? Blast crisis
- Bone marrow failure
- FBC: WCC may be > 50-400 x 109/L mostly neutrophils + myelocytes and metamyelocytes. High platelet count may also be seen
- BCR-ABL oncogene detectable by reverse transcriptase PCR (Philadelphia Chromosome)
- LAP score is low in leukaemia (LLL)
- Bone marrow is hypercellular with greatly increased WCC production
- Blood LDH levels is elevated
- High uric acid level due to increased cell breakdown.
Prognosis depends on
- Age at onset of the disease
- Phase of CML at time of diagnosis
- Number of blasts in the blood and bone
marrow at time of diagnosis
- Size of the spleen at the time of diagnosis
- Patient's general overall health
- Mainstay of treatment is the TKIs. There is Imatinib and several other new Tyrosine kinase inhibitors which give a 95% in the chronic phase.
- Imatinib and other TKIs block the action of the BCR-ABL fusion protein and leads to the disappearance of the Philadelphia chromosome in 90%.
- Patients are monitored by measuring and monitoring the BCR ABL transcript levels from baseline. Some develop resistance to the TKIs and there are now first and second-line TKIs
- Allogeneic HSCT is now reserved for patients who fail Tyrosine Kinase Inhibitor therapy.
- Blastic crises a combination of TKI and chemotherapy is given
- Hydroxycarbamide and low dose cytarabine can be used palliatively in older patients.