Chronic myeloid leukemia (CML) is a myeloproliferative disorder in which there is a neoplastic proliferation of mature granulocytes. The cancer results from a reciprocal translocation of the breakpoint cluster region (BCR) on chromosome 22 and the ABL1 gene region on chromosome 9 - t (9;22). The result is an abnormal fusion gene on chromosome 22 known as the Philadelphia chromosome. It represents 15% to 20% of all leukemias in the United States with an estimated incidence rate of 1 to 2 cases per 100,000. About 50% of affected individuals are asymptomatic. Diagnosis depends on demonstrating the presence of the Philadelphia chromosome. CML occurs in 3 phases. The most common is the chronic phase characterized by an indolent course and 30% blasts). Without treatment, progression is slow but relentless to the advanced stages and occurs over 3 to 5 years. Survival is markedly reduced once these latter stages are reached. The recognition that the BCR-ABL1 fusion gene was a key driver of the disease process led to the development of tyrosine kinase inhibitor (TKI) drugs that targeted the genetic basis for the cancer. The first of these was imatinib, which was released in 2001. Since then both second and third generations of the drug class have been approved. These medications have been demonstrated to reduce the ratio of abnormal to normal BCR:ABL1 transcripts. They are most effective if used in the chronic phase. The degree of this molecular response has been demonstrated to correlate with limitation of progression of disease and improvement, often marked, of survival. Most individuals who respond well require lifelong use of the medication. However, a subset of the responders may achieve treatment-free remission (TFR) without ongoing therapy. For those individuals who are in the advanced state of the disease, do not respond to the TKI drugs or cannot tolerate them, allogeneic hematopoietic stem cell transplantation (SCT) is an alternative therapy that can achieve long-term survival in some cases.
Clifton P Titcomb (Tue,) studied this question.