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Blastic Transformation
In the course of CML, there is sequential clonal evolution of stem cells bearing the original Ph1 chromosome. The newly evolved clones suppress the proliferation and differentiation of normal and preexisting Ph1 CML stem cells. Eventually, immature cells accumulate and the acute phase (blast crisis) develops. At a molecular level, there is no change in the bcr/abl gene activity. There is a high incidence of p53 mutations in association with blastic transformation of CML. Thus, it is possible that p53 mutation might complement the preexisting bcr/abl mutation and induce blastic transformation. Hyperploidy is more often associated with the myeloblastic acute phase, whereas hypoploidy or pseudodiploidy is more often associated with the lymphoblastic acute phase. Table 1 shows the poor prognostic factors in CML.

• Clinical
  
  
  • Older age
    
    
  • Symptoms at diagnosis
    
    
  • Significant weight loss
    
    
  • Hepatomegaly
    
    
  • Splenomegaly
    
    
  • Poor performance
    
    
  • Black race
    
    
• Laboratory
  
  
  • Anemia
    
    
  • Thrombocytosis,thrombocytopenia, megakaryocytopenia
    
    
  • Increased blasts or blasts and promyelocytes in blood or marrow
    
    
  • Increased basophils in blood or marrow
    
    
  • Collagen or reticulin fibrosis grades 3-4
    
    
• Treatment associated
  
  
  • Longer time to achieve hematologic remission with busulfan chemotherapy
    
    
  • Short remission duration
    
    
  • Total dose of busulfan or hydroxyurea therapy required in the first year to control the disease
    
    
  • Lack of significant suppression of Ph-positive metaphases with intensive chemotherapy or alpha-interferon therapy
    
    
  • Poor initial response to alpha-interferon therapy