Essay 8- MPN- classification. Chronic myelogenous leukemia (CML)
What are MPNs?
- The abnormal proliferation of one or more terminal myeloid cell lines in the peripheral blood gives rise to a heterogeneous group of disorders called myeloproliferative neoplasms:
- Chronic myeloid leukemia
- Polycythaemia vera
- Essential thrombocythaemia
- Primary myelofibrosis
WHO 2016 classification of MPN
Myeloproliferative neoplasms (MPN)
- Chronic myeloid leukemia (CML), BCR-ABL1+
- Chronic neutrophilic leukemia (CNL)
- Polycythemia vera (PV)
- Primary myelofibrosis (PMF)
- PMF, prefibrotic/early stage
- PMF, overt fibrotic stage
Essential thrombocythemia (ET)
- Chronic eosinophilic leukemia, not otherwise specified (NOS)
- MPN, unclassifiable
Mastocytosis
CML
Definition
- CML is defined as a myeloproliferative neoplasm predominantly composed of proliferating granulocytes and determined to have the Philadelphia chromosome
- Translocation t(9;22)
- Associated with erythroid and platelet hyperplasia!
- Affects both peripheral blood and BM!
Etiology
- 90% of cases are due to a reciprocal translocation of chromosomes 9 and 22 resulting in the Philadelphia chromosome!
- As a result of which part of the oncogene ABL1 is moved to the BCR gene on chromosome 22
- The resulting gene called BCR-ABL1 codes for a fusion protein which has excess tyrosine kinase activity
Symptoms
- 30% are asymptomatic at time of diagnosis
- Symptoms occur gradually:
- Easy fatigue
- Malaise
- Anorexia
- Abdominal discomfort
- Weight loss
- Pallor
- Bruising, epistaxis, menorrhagia
- Splenomegaly
- Sternal pain
- Less frequent symptoms:
- Night sweats
- Heat intolerance (mimicks hyperthyroidism)
- Gouty arthritis
- Splenic infarction
Diagnosis
- History
- Physical exam
- Presence of BCR-ABL1 gene fusion by RT-PCR analysis
- Serum uric acid is raised
- Labs:
- Chronic phase
- Peripheral smear- leucocytosis
- Higher proportions of mature segmented Neu and myelocytes
- Blast cells less than 10% of WBC
- Increase Ba and Eo
- Bone marrow aspirate and biopsy- hypercellularity with marked granulocytic proliferation and increased myelocytes
- Accelerated phase
- Peripheral smear- may or may not show increased blasts
- Bone marrow aspirate and biopsy- similar changes to chronic phase CML with increased blasts
- Blast phase
- Peripheral smear and BM aspirate- greater than 20% blasts!
DD
- Polycythaemia vera
- Myelofibrosis
- Essential thrombocytemia
- Extreme reactive leukocytosis
Treatment
- Tyrosine kinase inhibitors are the mainstay of treatment of CML
- First line includes:
- Imatinib
- Nilotinib
- Dasatinib
- TKI should be monitored for BCR-ABL1 transcripts in marrow or blood and/or karyotypic analysis of the bone marrow
- Allo-SCT for people who fail treatment with TKI