What is Chronic Myeloid Leukemia (CML)?
CHRONIC MYELOID LEUKEMIA (CML), as the name implies, is a chronic or slow-growing progression of a disease of myeloid cells (a type of White blood cells that become mature red blood cells, white blood cells and platelets). In chronic myeloid leukaemia, the bone marrow produces too many myeloid blood cells which are at various maturation stages including cells known as immature granulocytes, metamyelocyte, and myeloblasts.
What are the Symptoms of CML? What is the Natural Course of the Disease?
The common symptoms of CML are-
- Fatigue
- Bleeding – Due to Low platelets OR dysfunctional platelets
- Abdominal Pain and discomfort – due to Enlarged Spleen (Splenomegaly) and Liver (hepatomegaly).
How common is CML and What is the Age Group?
CML is usually diagnosed in 5th – 6th decade worldwide but in India, where it forms nearly 40-50 % of all Leukemias, it is diagnosed a decade earlier.
What Causes Chronic Myeloid Leukemia?
In 95 % of patients, there is swapping between a part of chromosomes number 9 and 22 which is also called TRANSLOCATION – t(9:22). This results in the production of a product called bcr-abl which results in impaired maturation and prevents cell death and enhances expansion of abnormal clone.
How is Chronic Myeloid Leukemia Diagnosed?
The following tests help in diagnosis –
- Peripheral blood examination and Complete blood picture.
- RT- PCR testing for bcr-abl transcript
- Bone Marrow Evaluation for KARYOTYPING
What are the stages of Chronic Myeloid Leukemia?
- CHRONIC PHASE- Slow-growing disease (a most common form of presentation)
- ACCELERATED PHASE - Rapid increase in premature forms
- BLAST PHASE- or Acute Leukemic phase
How is Chronic Myeloid Leukemia Treated?
The first-line treatment of CML in most situations is an oral medication. These pills have transformed the way we treat CML and have enabled a CML patient to lead a life like any other individual.
Generations of these drugs-
- First Generation – Imatinib
- Second Generation – Nilotinib and Dasatinib
- Third Generation – Bosutinib and Ponatinib
Imatinib was the first in a class of targeted therapies in cancer and it unleashed the era of precision medicine in cancer. 90% of patients initially started on Imatinib survived for nearly a decade during Follow up.
Regular Monitoring of the bcr-abl Transcript is required during the course of treatment and is possible by a simple blood test also called RQ-PCR.
Upon development of resistance to first-line treatment again precision medicine is used to point out the new aberrant mutation and the drug is chosen as per sensitivity.
Patients attaining deep response and durable ones lasting for nearly more than 2 years can also be considered for holding treatment but also require more intensive monitoring thereafter.
In Blast phase and accelerated phase, these oral medications are used as a bridge to allogeneic transplant in eligible patients.
Should therapy be changed for CML patients already on treatment in the presence of COVID-19 pandemic?
Treatment should not be changed for patients who are asymptomatic and do not have documented infection with SARS-Cov-2. There is no increased Immunosuppression with the current use of TKI. There are pulmonary side effects associated with some TKIs, such as pleural effusion and pulmonary arterial hypertension, most common with dasatinib, which in theory might complicate or add to morbidity from severe SARS-CoV-2 infection. These adverse events should be managed as per standard practice.