Chronic Myelogenous Leukemia (CML)
Definition
- Pluripotent myeloproliferative neoplasm associated with BCR-ABL1 fusion gene in the Philadelphia chromosome
Alternate/Historical Names
- Chronic granulocytic leukemia
- Chronic myeloid leukemia
Diagnostic Criteria
- CML is characterized by a chronic phase that generally progresses to a blast phase, frequently passing through an accelerated phase
- Chronic phase is characterized by leukocytosis and hypercellular marrow
- Peripheral blood leukocytosis
- Granulocytes at all stages of maturation
- Two peaks: segmented neutrophils and myelocytes
- Basophilia
- Eosinophilia (frequent)
- Special forms may have prominent thrombocytosis, monocytosis, neutrophilia
- Granulocytes at all stages of maturation
- Mild anemia
- Hypercellular marrow
- Myeloid:erythroid ratio >10:1
- Granulocytes at all stages of maturation
- Thickened peritrabecular cuff of immature myeloids
- 5-7 cells thick vs 2-3 normal
- Mature neutrophils in intertrabecular space
- Blasts <10% and usually <2%
- Small hypolobated megakaryocytes ("dwarf megakaryocytes")
- Basophils and eosinophils elevated
- Variable fibrosis
- Pseudo-Gaucher histiocytes
- Peripheral blood leukocytosis
- Progression generally occurs to an accelerated phase and then to blast phase
- Any one of the following indicates progression to accelerated phase
- Cytogenetic evidence of clonal evolution
- Change from initial karyotype
- Persistent thrombocytopenia <100 x 103/μL
- Lack of response to therapy
- Persistent thrombocytosis >1000 x 103/μL OR
- Persistent or increasing splenomegaly OR
- Persistent or increasing leukocytosis >10 x 103/μL
- Following criteria of accelerated phase are also associated with transition to blast phase
- Blasts elevated to 10-19% in blood or marrow
- Peripheral blood basophilia ≥20%
- Cytogenetic evidence of clonal evolution
- Blast phase may develop following accelerated phase or directly from chronic phase
- Defined as either:
- >20% blasts in marrow or blood, OR
- Presence of an extramedullary blast proliferation
- 2/3 of cases myeloid
- 1/3 lymphoid
- Improved survival
- Mostly precursor B
- Rarely T cell
- Defined as either:
- BCR-ABL1 fusion gene results in the Philadelphia chromosome in 90-95% of cases (cytogenetic study)
- Remaining cases appear to have variant or cryptic translocations detectable by RT-PCR or FISH
- Rare BCR-ABL1 negative cases have been proposed
- Must be tested by RT-PCR and/or FISH
- Some may represent CMML or atypical CML
- BCR-ABL1 is necessary but not sufficient for the diagnosis of CML
- B lymphoblastic leukemia is BCR-ABL+ in 30% of adult cases
- Rare p230 BCR-ABL1 isoform can present with thrombocytosis and /or neutrophilia
Dita Gratzinger MD PhD
Tracy I George MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting: 10/23/11
