Many cancers are treated with an endpoint of removal of the primary tumor and metastases so that grossly and microscopically, the body is nearly free of tumor cells. In the case of blood cancers, however, the endpoint is different where a complete normalization of blood cell count is necessary to ensure that the body is free from cancer. In the case of chronic myeloid leukemia, we go a step further by ensuring what we call a “molecular remission”. In this case, the body is not only free of cancer cells, but also free of all genes related to the cancer itself. Therefore, the genetic defect responsible for the cancer is eliminated. This genetic defect is called the BCR/ABL fusion gene. To simplify things, chronic myeloid leukemia can be treated, but also cured.
The main obstacle in the treatment of chronic myeloid leukemia is the development of a blast crisis. The disease remains in the chronic stage for years before proceeding to an accelerated phase followed by a blast crisis with life-threatening consequences. Treatment aims to prevent the development of a blast crisis and to treat it if it occurs. The treatment of chronic stage CML yields excellent results with first-class drugs in most cases, but treatment during the accelerated phase or blast crisis yields worse results and second-class drugs or even stem cell transplantation are considered in such cases. Complete remission from CML is measured by the absence of Philadelphia chromosome or BCR/ABL gene by a test called a PCR or a polymerase chain reaction, which detects fragments of DNA.
Tyrosine kinase inhibitor (Imatinib)
The introduction of tyrosine kinases was revolutionary in the management of chronic myeloid leukemia since they act directly on the gene responsible for cancer -The BCR/ABL gene-. They also induce cells with this defect to undergo apoptosis or “suicide”, thus preventing them from dividing.
The results of treatment with Imatinib in chronic myeloid leukemia during the chronic stage are near perfect, with an average of 94% of patients responding to this therapeutic approach. The main challenge, however, is the treatment of patients during blast crisis since they tend to have a non-optimal response with imatinib as a primary therapy. It is also well tolerated by the majority of patients at its most commonly used dosage of 400mg/day. The main side effects of imatinib are swollen legs and eyes, diarrhea, anemia and rash.