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Blast crisis is the final stage of chronic myeloid leukemia, characterized by the abnormal accumulation of immature white blood cells and blasts. The Philadelphia chromosome, present in 95% of patients with CML, is a key factor in the development of blast crisis, which is highly resistant to treatment. Symptoms include fatigue, bleeding, and abdominal enlargement, and myeloid sarcomas can develop in various tissues. Certain factors increase the risk of developing leukemia, including radiation, smoking, and inherited conditions.
A blast crisis is the final stage of chronic myeloid leukemia (CML) — cancer of white blood cells with uncontrolled proliferation and abnormal accumulation of cells in the bone marrow and blood. Blast crisis is diagnosed when more than 20% of the white blood cells and lymphocytes in the blood or bone marrow are immature, poorly differentiated cells or blasts. Other key indicators include the finding of large clusters of blasts in the bone marrow obtained by biopsy and the formation of a solid tumor outside the bone marrow, called myeloid sarcoma. Chronic myeloid leukemia usually progresses to rapidly progressive blast crisis within about 20 to 29 years of diagnosis, although patients aged 20 to 29, due to the more aggressive nature of their leukemia, may present in blast crisis. Treatment approaches are generally ineffective at this stage, with only about 100% of patients surviving the crisis.
The initial event in the sequence culminating in blast crisis is the acquisition within bone marrow stem cells of the Philadelphia chromosome, named after the city in which it was isolated. Easily recognizable under a microscope, the Philadelphia chromosome is a translocation of genes between chromosomes 22 and 9. This genetic marker is present in 95% of patients with CML. The abnormal chromosome causes uncontrolled proliferation and increased survival of the abnormal blast cells. Despite many advances in leukemia treatments, Philadelphia chromosome changes make blast crisis highly resistant to therapy, with favorable responses occurring in only 20% of cases.
Research shows that certain factors increase a patient’s risk of developing leukemia. Radiation, cigarette smoking, benzene exposure and chemotherapy have all been implicated in cases of leukemia. Down syndrome and other inherited conditions can also increase the risk of leukemia. There is also a rare leukemia linked to human T-cell leukemia virus type I.
Symptoms of blast crisis can include fatigue, malaise, low-grade fever, bleeding, bruising, and abdominal enlargement. Patients may have swollen lymph nodes and pain in the bones or joints. They may be susceptible to frequent infections and may experience weight loss for no apparent reason. These symptoms occur due to the crowding out of the normal components of the bone marrow by the abnormal stem cells, thereby decreasing the production of functional red blood cells, white blood cells, and platelets. The spleen, acting like a filter, enlarges as abnormal cells become trapped within its tissues.
Myeloid sarcomas, typically found in blast crisis, can develop in any tissue or organ, but the most commonly involved areas are the gums and skin. Gum involvement produces swollen, tender areas that bleed easily with brushing and flossing. Skin sarcomas appear as purplish-red nodules infiltrated with white blood cell blasts. Other potential sites for myeloid sarcoma include the chest cavity, lymph nodes, lining of the brain, small intestine, ovaries, and uterus. Unlike bone marrow sites, myeloid sarcomas usually respond well to standard anti-leukemia chemotherapy.
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