Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that affects the blood and bone marrow. It is characterized by the overproduction of abnormal white blood cells in the bone marrow, leading to an accumulation of these cells in the blood.

CML is caused by a genetic abnormality known as the Philadelphia chromosome, which is a result of a translocation between chromosomes 9 and 22. This translocation leads to the formation of a fusion gene called BCR-ABL1. The BCR-ABL1 gene produces an abnormal protein that promotes the uncontrolled growth and division of white blood cells, specifically granulocytes.

The onset of CML is usually insidious, with most patients being asymptomatic during the early stages. As the disease progresses, symptoms may include fatigue, weakness, weight loss, night sweats, fever, abdominal pain, and an enlarged spleen. CML is often detected during routine blood tests when an elevated white blood cell count or the presence of immature white blood cells, called blasts, is observed.

The management and treatment of CML have been revolutionized by the development of targeted therapy called tyrosine kinase inhibitors (TKIs). TKIs, such as imatinib, dasatinib, and nilotinib, work by inhibiting the activity of the BCR-ABL1 protein, thereby blocking the abnormal signaling pathways and reducing the production of abnormal white blood cells. These medications have significantly improved the prognosis for CML patients, leading to high response rates and prolonged survival.

Treatment for CML is typically divided into three phases: chronic phase, accelerated phase, and blast crisis. The goal of therapy is to achieve and maintain a deep molecular response, which means that the level of BCR-ABL1 transcripts in the blood becomes undetectable or extremely low. In the chronic phase, most patients can achieve a durable response and lead normal lives with ongoing TKI therapy. However, some patients may progress to the accelerated phase or blast crisis, which are associated with more aggressive disease and poorer outcomes.

In some cases, when TKIs are not effective or well-tolerated, or if the disease progresses despite treatment, other options may be considered. These include hematopoietic stem cell transplantation (HSCT), which involves replacing the diseased bone marrow with healthy stem cells from a compatible donor. HSCT is a potentially curative treatment option but is associated with significant risks and complications.

Regular monitoring of CML patients is crucial to assess response to treatment, detect any signs of disease progression, and manage side effects of therapy. It is important for patients to work closely with their healthcare team and adhere to the prescribed treatment plan. With appropriate treatment and ongoing monitoring, the outlook for most CML patients has greatly improved, and many can live long and productive lives.