Leukaemia (chronic myeloid)

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that originates in the bone marrow and affects the blood. It primarily involves the overproduction of myeloid cells, which are a type of white blood cell.

Key Points about CML

Pathophysiology:
- CML is characterized by the presence of the Philadelphia chromosome, a genetic abnormality resulting from a translocation between chromosomes 9 and 22. This translocation creates the BCR-ABL fusion gene, which produces an abnormal tyrosine kinase protein that drives the proliferation of myeloid cells.
- The disease progresses through three phases: chronic phase, accelerated phase, and blast crisis.
Symptoms:
- Many patients are asymptomatic in the early stages and are diagnosed through routine blood tests.
- Symptoms, when present, may include fatigue, weight loss, night sweats, fever, and splenomegaly (enlarged spleen), which can cause abdominal discomfort.
Diagnosis:
- CML is often diagnosed based on blood tests showing elevated white blood cell counts.
- The definitive diagnosis is made through genetic testing that identifies the Philadelphia chromosome or the BCR-ABL gene fusion.
- Bone marrow biopsy may be performed to assess the degree of bone marrow involvement and to help in staging.
Staging and Prognosis:
- CML is staged based on the percentage of blast cells (immature white blood cells) in the blood or bone marrow.
- Chronic phase: fewer than 10% blasts.
- Accelerated phase: 10-19% blasts.
- Blast crisis: 20% or more blasts, resembling acute leukemia.
- Prognosis is generally good with current treatments, particularly for those diagnosed in the chronic phase.
Treatment:
- The introduction of tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nilotinib has revolutionized CML treatment, turning it into a manageable chronic condition for many patients.
- Treatment goals include achieving hematologic remission (normal blood counts), cytogenetic remission (absence of the Philadelphia chromosome), and molecular remission (undetectable BCR-ABL transcripts).
- In cases where TKIs are ineffective or not tolerated, alternative treatments such as allogeneic stem cell transplantation may be considered.
Risk Factors:
- The exact cause of CML is not known, but exposure to high doses of radiation is a known risk factor.
- It is more common in older adults, with the median age at diagnosis being around 60-65 years.
Research and Advances:
- Ongoing research focuses on improving the effectiveness of TKIs, overcoming resistance to treatment, and developing new therapeutic approaches.
- Clinical trials are exploring combination therapies and novel agents targeting different pathways involved in CML.

Summary

Chronic myeloid leukemia is a type of blood cancer characterized by the overproduction of myeloid cells due to the BCR-ABL fusion gene. With the advent of tyrosine kinase inhibitors, the prognosis for CML patients has improved significantly, allowing many to manage the disease as a chronic condition. Early diagnosis and targeted treatment are key to achieving long-term remission and improving quality of life for patients with CML.

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