From the Guidelines
Blast crisis diagnosis should include a complete blood count (CBC) with differential, peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry, cytogenetic analysis, and molecular studies, as recommended by the most recent guidelines 1. The diagnosis of blast crisis is critical for the management of chronic myeloid leukemia (CML) and other myeloproliferative disorders.
- The initial step in diagnosis is a CBC with differential to assess for severe anemia, thrombocytopenia, and leukocytosis with increased blast percentage (typically >20% in peripheral blood) 1.
- A peripheral blood smear can identify blast morphology, while bone marrow examination confirms the diagnosis by revealing blast infiltration 1.
- Flow cytometry determines the lineage of blasts (myeloid vs. lymphoid), which guides treatment decisions 1.
- Cytogenetic analysis identifies chromosomal abnormalities like Philadelphia chromosome or complex karyotypes, and molecular studies detect specific mutations like BCR-ABL1 fusion gene 1.
- Additional tests should include comprehensive metabolic panel, coagulation studies, and HLA typing if stem cell transplantation is considered 1. The European LeukemiaNet defines CML-BP as 30% or more blast cells in blood or bone marrow and/or the demonstration of extramedullary blastic infiltrates with the exception of the liver and spleen 1.
- The World Health Organization and recent International Consensus Classification (ICC) classification sets the threshold value for blasts at 20% 1.
- The detection of lymphoblasts in peripheral blood or bone marrow, even in the range below 10%, is generally considered consistent with the diagnosis of blast phase 1.
- An extended diagnostic workup should be completed for pediatric patients who meet the criteria for CML-BP, including BCR::ABL1 mutation testing by NGS 1.
From the FDA Drug Label
Grade 3 or 4 elevations of transaminases or bilirubin and Grade 3 or 4 hypocalcemia, hypokalemia, and hypophosphatemia were reported in patients with all phases of CML but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML.
Table 13: CTC Grade 3/4 Laboratory Abnormalities in Clinical Studies of CML in Adults: Resistance or Intolerance to Prior Imatinib Therapy ... Myeloid Blast Phase (n=74) Lymphoid Blast Phase (n=33) Percent (%) of Patients Hematology Parameters* Neutropenia 77 79 Thrombocytopenia 78 85 Anemia 74 52 Biochemistry Parameters Hypophosphatemia 12 18 Hypokalemia 11 15 Hypocalcemia 9 12 Elevated SGPT (ALT) 5 3 Elevated SGOT (AST) 4 3 Elevated Bilirubin 3 6 Elevated Creatinine 8 0
The laboratory findings for a patient in blast crisis include:
- Hematology parameters:
- Neutropenia (77-79% of patients)
- Thrombocytopenia (78-85% of patients)
- Anemia (52-74% of patients)
- Biochemistry parameters:
- Hypophosphatemia (12-18% of patients)
- Hypokalemia (11-15% of patients)
- Hypocalcemia (9-12% of patients)
- Elevated liver enzymes (SGPT/ALT: 3-5% of patients, SGOT/AST: 3-4% of patients)
- Elevated bilirubin (3-6% of patients)
- Elevated creatinine (0-8% of patients) 2
From the Research
Laboratory Findings for Blast Crisis
The laboratory findings for a patient in blast crisis, a state of acute leukemia characterized by an increased number of blast cells, can be summarized as follows:
- Increased white blood cell count [ 3 ]
- Bone marrow analysis showing an increased number of blasts [ 4 ]
- Immunophenotyping by flow cytometry to determine the lineage of the blasts [ 4 ]
- Detection of the Philadelphia chromosome by chromosome study [ 4 ]
- Cytogenetic analysis to detect additional chromosomal aberrations [ 5 ]
- Molecular genetic analysis to detect BCR/ABL amplification [ 5 ]
Cytogenetic and Molecular Genetic Findings
Cytogenetic and molecular genetic findings in blast crisis can include:
- Acquisition of new chromosome abnormalities in addition to the t(9;22) translocation [ 5 ]
- BCR/ABL amplification, which can be a mechanism of acquired resistance to tyrosine kinase inhibitors [ 5 ]
- Multiple secondary cytogenetic abnormalities, including homogeneously staining regions [ 5 ]
Treatment and Prognosis
Treatment and prognosis for blast crisis can be influenced by the laboratory findings, including: