Chronic myeloid leukemia (CML)

Disease information

Overview
Causes
and Symptoms
Treatment

Overview

Chronic Myeloid Leukemia (CML) makes up about 15% of all adult leukemia cases. Each year in Korea, it's estimated that 400 to 500 new cases are diagnosed. The number of people undergoing treatment for CML is on the rise, thanks to the success of targeted cancer drugs known as tyrosine kinase inhibitors, which have been in use since 2001. These drugs help people with CML live longer. On average, people diagnosed with CML are between 50 and 60 years old. But it's not just a disease of the middle-aged - over 20% of CML patients are over 70. CML is quite rare in children and teenagers, representing less than 5% of all CML cases.

Causes and Symptoms

The exact causes of Chronic Myeloid Leukemia (CML) are not fully understood. In CML, part of chromosome 9 attaches itself to the end of chromosome 22, creating what's known as the Philadelphia chromosome, a shorter version of chromosome 22. This results in a fusion of the BCR gene from chromosome 22 and the ABL1 gene from chromosome 9, creating the BCR-ABL1 fusion gene. This fusion gene produces a cancerous protein that triggers harmful changes in blood stem cells, causing them to multiply much more quickly than normal.
While it's unclear why the BCR-ABL1 cancer gene forms, it seems to happen more often in people who have long-term exposure to certain substances, such as ionizing radiation, radioactive isotopes, benzene toluene, dyes, and heavy metals. However, in most cases, there's no specific cause. If a newly diagnosed patient suspects their occupation may have contributed to their illness, they could discuss the possibility of workers' compensation with a specialist at Seoul St. Mary's Hospital.

CML is typically categorized into three stages: the chronic phase, the accelerated phase, and the blast phase. About 93% of patients who come to the hospital for the first time are in the chronic phase; 5% are in the accelerated phase, and about 2% are in the blast phase.

Unlike acute leukemia, the symptoms of CML in the chronic phase develop slowly over several months. Many patients are diagnosed when abnormal blood levels are found during routine check-ups for unrelated issues or minor fatigue.

Mild fatigue, cold sweat, and hot flush
Weight loss, abdominal distention, upper-left abdominal pain, and enlarged spleen

▲ A symptom of mild fatigue

Patients with chronic myeloid leukemia can progress to the blast phase three to four years later if not treated properly. Only immature hematopoietic stem cells are produced when the disease progresses to the accelerator or blast phase, and blood components are insufficient; a decrease in white blood cells reduces immunity; and a lack of red blood cells and platelets can't cause anemia and blood to stop easily.

Treatment

Targeted therapy (tyrosine kinase inhibitors, TKIs)

①
1th Gen (Imatinib)
②
2th Gen (Tasigna, Sprycel, Bosulif, Supect)
- Second-generation TKIs have been developed that can suppress many point mutations showing resistance to Gleevec, and thus regain good therapeutic effects. In Korea, these second-generation TKIs have been approved and are being prescribed as first or second-line therapy.
③
3th Gen (Iclusig)
- The characteristic feature is that it shows a certain degree of positive effect even on leukemia cells that have not responded to multiple targeted anticancer drugs, or on cells with a T315I point mutation.
④
4th Gen (Asciminib)
- This is a targeted anticancer drug that exhibits effects by binding to different sites than 1st, 2nd, and 3rd generation TKIs.

Hydrea

It is a general oral chemotherapy used to control the number of white blood cells that are initially increased or when there is no more treatment.

Injection chemotherapy and Hematopoietic stem cell transplantation

It is applied restrictively in cases where all targeted therapy have failed or are resistant. For patients diagnosed in the blast phase, allogeneic hematopoietic stem cell transplantation can be considered after chemotherapy treatment to revert back to the chronic phase.