Philadelphia chromosome and disease phases
The breakdown occurs in one stem cell of the bone marrow and is not inherited. The resulting BCR-ABL protein continuously sends a signal to divide, causing granulocyte cells to multiply without stopping. The disease goes through three phases. In the chronic phase, in which it is usually detected, the state of health is satisfactory, and the cells are still maturing. In the acceleration phase, the number of immature forms increases and new chromosomal changes appear. Blast crisis resembles acute leukemia and requires intensive treatment. The goal of therapy is to keep the disease in the chronic phase.
- Exchange of regions between chromosomes 9 and 22
- BCR-ABL gene and its continuously active protein
- The chronic phase is the most common in diagnosis
- Acceleration phase with growth of immature cells
- Blast crisis as the most severe option
- The damage is acquired and cannot be inherited.
Symptoms
In about half of patients, the disease is discovered incidentally during a routine blood test done for another reason. When complaints appear, they are nonspecific: increasing fatigue, weakness, loss of appetite, sweating, low fever, weight loss. An enlarged spleen causes heaviness and distension in the left hypochondrium, a feeling of rapid satiety even from a small portion of food. Bone pain is less common. When the number of leukocytes is very high, the blood becomes viscous, which can manifest itself as blurred vision, tinnitus, and headache.
- Fatigue and weakness
- Heaviness and distension in the left hypochondrium
- Quick satiety when eating
- Sweating and low-grade fever
- Weight loss
- Bone pain
- Visual impairment with very high leukocytosis
Diagnostics
In a general blood test, attention is paid to a sharply increased number of leukocytes with all intermediate forms of maturation, an increase in basophils and eosinophils, and often increased platelets. The diagnosis is confirmed by identifying the BCR-ABL gene using PCR in the blood or bone marrow and detecting the Philadelphia chromosome during cytogenetic examination of the bone marrow. Bone marrow examination is also necessary to determine the phase of the disease and identify additional chromosomal changes. Ultrasound evaluates the size of the spleen, and biochemistry evaluates uric acid, LDH and kidney function before starting treatment.
- General blood test with leukemia formula
- Analysis for BCR-ABL by PCR
- Bone marrow cytogenetics and the search for the Philadelphia chromosome
- Bone marrow aspirate and biopsy to determine phase
- Ultrasound of the spleen and liver
- Uric acid, LDH, creatinine
Treatment with tyrosine kinase inhibitors
The basis of therapy is tableted tyrosine kinase inhibitors that block the BCR-ABL protein. They are taken daily and over a long period of time, and effectiveness is assessed by reducing the amount of BCR-ABL in the blood within a specified time frame. Achieving a deep molecular response means the disease is under control. In some patients with a sustained deep response, the physician may discuss trying to discontinue the drug under close supervision, but this should not be decided independently. In case of resistance or intolerance, the drug is changed, and bone marrow transplantation is considered during progression and in selected situations.
- Taking a tyrosine kinase inhibitor daily
- Control of BCR-ABL at the appointed time
- Changing the drug if there is resistance or side effects
- Bone marrow transplantation during progression
- Control uric acid and drink plenty of fluids at the beginning of treatment
- Do not skip an appointment or stop treatment on your own
- Check with your doctor about any other medications and grapefruit juice
Observation and lifestyle
Regularity of taking the drug is the main factor of success: omissions significantly worsen the response, so reminders and linking the intake with usual activities are useful. You should tell your doctor about side effects - swelling, nausea, skin rashes, muscle pain, since they can be reduced by adjusting the dose or replacing the drug, and not by stopping it yourself. The BCR-ABL test is carried out on schedule, in the same laboratory, so that the results are comparable. Pregnancy with CML is planned only together with a hematologist, since most drugs are not used during this period.
- Strict adherence to the dosage regimen
- Tell your doctor about side effects rather than stop treatment
- Take BCR-ABL on schedule and in one laboratory
- Discuss any new drugs with a hematologist
- Plan pregnancy only in consultation with your doctor
- Vaccination in consultation with a doctor
- Drinking enough and eating a balanced diet
