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Isabella Martire, MD, Board Certified In Oncology
CML A Success Story
Isabella C. Martire, MD, AC
. https://www.isabellamartire-md.com/

CML A Success Story

Patients with the diagnosis of CML or Chronic Myelogenous Leukemia prior to the year 2000 had an average survival of six years with bone marrow transplant.

Currently, the average survival of a CML patient is >30 years without the need of bone marrow transplant by utilizing oral targeted therapies.

How did that success come about? In 1973, the chromosomal abnormality linked to CML was identified, the 9 22 translocation called Philadelphia Chromosome responsible for the creation of the bcr-abl oncogene. The bcr-abl oncogene encodes for a protein kinase that in turn is responsible for the incessant cell proliferation in CML.

In 1992, a bcr-abl protein kinase inhibitor was synthesized and subsequently tested in humans causing prolonged remission in >80% of CML patients. The drug known by the name of gleevec was FDA approved by 2000, an oral tyrosine kinase inhibitor that transformed a highly lethal disease into a chronic disease. A small number of patients were noted to relapse after an initial response to gleevec. These particular patients were noted to have different molecular variants that have since been targeted with different oral kinase inhibitors.

The first tyrosine kinase inhibitor available to treat CML was gleevec or imatinib, which gives complete hematologic remission in 88% of patients in chronic phase and major cytogenetic response in 49%.

The newer generation tki's are even more powerful although somewhat more toxic. Dasatinib or sprycel has been associated with plural effusions, and nilotinib or tasigna with elevated liver function test's and qt prolongation on the EKG (electrocardiogram).

These new kinase inhibitors in view of higher responses even in patients resistant to gleevec are currently first line therapy.

Additional kinase inhibitors are currently being developed as well. The new generation tki's bosotunib has been studied as front line therapy with good results. On the horizon is a multikinase inhibitor called ponatinib for patients that harbor T3I5I mutation. Also, a small-molecule inhibitor called omacetaxine is currently being tested in imatinib resistant patients.

The treatment options for CML in 2011 are numerous and very effective in the majority of cases with an average survival rate > 30 years.

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