Q5: Why should chronic granulocytic leukemia be medicated as soon as possible after diagnosis?
A: Chronic granulocytosis is divided into chronic (early), accelerated (intermediate) and acute (late) phases.
Fortunately, most patients are in the early stage when they are diagnosed with chronic granulocytic leukemia, and clinical data from home and abroad confirm that early medication is the most effective and can better control the disease. If they enter the accelerated or even acute phase, the biological characteristics of leukemia have changed, so it is not only more difficult to treat, but also difficult to achieve better results with medication. Wei-Ming Lai, Department of Hematology, Wuhan Union Medical College Hospital
In addition, some patients in the chronic stage, even without special drugs, may not experience serious symptoms for 2-3 years and feel good about themselves, so they are reluctant to take tyrosine kinase inhibitors (TKI) and other drugs with better efficacy but relatively high prices; or they may take TKI drugs initially and then stop or reduce the dosage as their symptoms get better. All these behaviors may lead to the deterioration of the disease into the middle and late stages, at which time it is difficult to achieve satisfactory results with medication.
Q6: Can chronic granulocytic leukemia be cured?
A: This question cannot be answered simply as to whether it can or cannot.
Different doctors will use different treatments for the same individual based on their clinical experience, and different treatments have different “cure” ratios and, of course, different risks of failure.
The same treatment method may also produce different results for different individuals.
Personally, I believe that if the patient and the doctor work together, most of the slow particles can be better controlled and some can be cured.
For example, bone marrow transplantation is currently recognized as a better cure for chronic granulocytosis, with a cure rate of about 80% for patients in the chronic stage.
Of course, bone marrow transplantation requires certain prerequisites, such as a young age (under 50 years old), a matched donor (preferably a sibling), and hundreds of thousands of dollars of financial support (at least $250,000, depending on the condition, donor match, etc.).
However, it must be said that transplantation still has a failure rate of nearly 20% due to transplantation-related complications such as rejection, infection, bleeding, etc., and transplantation failure means that the patient is at risk of losing his or her life.
The most widely used treatment modality is tyrosine kinase inhibitor (TKI) therapy (the first-generation drug is Imatinib, the second-generation drugs are Nilotinib and Dasatinib, and the third-generation drugs are available abroad). Clinical data have confirmed that about 50% of patients who have been on the drug for several years can achieve profound remission, and a few of these patients can stop the drug and achieve “clinical cure” or “treatment-free remission”.
However, other therapies such as interferon, cytarabine or hydroxyurea are not very effective in chronic granulocytic leukemia.
Q7: How long can I live after the diagnosis of chronic granulocytic leukemia?
A: Since the introduction of tyrosine kinase inhibitors (TKI) more than a decade ago, significant progress has been made in the treatment of chronic granulocytic leukemia.
According to the latest authoritative clinical data in the United States, patients treated with TKI (any age group from 15 to 85 years old) have the same 5-year survival rate as the general population, reaching about 90%.
In other words, if TKI therapy is applied in a standardized manner, about 90% of patients can survive for a long period of time, thus transforming TKI from a malignant neoplastic disease to a common, manageable chronic disease like hypertension and diabetes.
However, it should be emphasized that the prerequisite of “good efficacy” is the standardized and rational use of drugs. First, the dosage of drugs should be standardized. Inadequate dosage and arbitrary reduction of dosage will affect the efficacy; second, the side effects of drugs should be treated correctly and properly; doctors with rich clinical experience can better judge and grasp the use of drugs and the management of side effects. Finally, regular and timely monitoring can help to detect adverse effects and adjust the treatment plan in time.
Simply put, as long as reasonable and standardized treatment and monitoring are ensured, the vast majority of patients can survive for a long time.
Q8: Do I have to use tyrosine kinase inhibitors (Imatinib, Nilotinib, Dasatinib, etc.) after the diagnosis of chronic granulocytic leukemia?
A: As stated in Q3, Ph chromosomal translocation is the underlying cause of the pathogenesis of slow-onset granulocytosis, and the resulting BCR/ABL fusion gene, encoding a protein that causes enhanced tyrosine kinase activity, is the pathogenesis of slow-onset granulocytosis.
The molecular mechanism of tyrosine kinase inhibitor (TKI) action is to act as a competitive inhibitor of ATP, blocking the phosphorylation of tyrosine kinase (TK) and inhibiting BCR-ABL expression, thus preventing the growth of tumor cells and leading to their death.
Imatinib, as the world’s first molecularly targeted drug, is able to act precisely on slow-acting granulocytes with less impact on normal cells, which not only has better efficacy but also less side effects.
As stated in Q7, 90% of patients treated with TKI can survive for a long period of time; and because of its convenience and low side effects, patients can generally work and live normally. Therefore, the current medical guidelines for the treatment of chronic granulocytes at home and abroad recommend tyrosine kinase inhibitors (TKI) as the first choice for the treatment of chronic granulocytes, and then switch to other treatment options if the treatment is not effective.
Q9: If I cannot afford the cost of TKI treatment, are there other ways to treat LRD?
A: First, as mentioned in Q6, bone marrow transplantation is an option with a high probability of cure, but because of its prerequisites and associated complications, transplantation is currently used as a second-line treatment option only when TKI is not effective.
More powerful second-generation drugs, nilotinib and dasatinib, have also been marketed. Several third-generation drugs that have recently been marketed abroad will soon enter the domestic market as well. Therefore, in case of poor efficacy or intolerable side effects of one TKI, switching to another TKI will be considered first (e.g., replacing the first-generation drug imatinib with the second-generation drugs nilotinib or dasatinib; if the efficacy is still poor, then bone marrow transplantation will be considered.
Second, for patients who are unable to undergo bone marrow transplantation before the availability of TKI, treatment with interferon + low-dose cytarabine is generally recommended. This treatment is less expensive than TKI and has an effective rate of about 30%, which is far less than the efficacy of TKI, let alone cure or discontinuation.
However, there are still very poor patients who can only be treated with inexpensive oral drugs such as hydroxyurea. This treatment can reduce elevated white blood cells, normalize blood count, shrink the spleen, and achieve some superficial efficacy. However, as mentioned in previous question 5, slow granulocytes are divided into chronic, accelerated and acute phases, and some patients can maintain the chronic phase for 2-3 years even without the use of specific drugs, before entering the accelerated acute phase. Hydroxyurea only reduces white blood cells without any control of disease progression. The temporary symptom relief brought by treatment with this drug tends to paralyze the patient and delay the disease.
Happily, domestic TKI drugs are available and TKI (1st and 2nd generation) are gradually entering the medical insurance reimbursement list in many regions, which undoubtedly help patients to choose to receive TKI treatment.
Q10: Why are tyrosine kinase inhibitors (Imatinib, Nilotinib, Dasatinib, etc.) targeted therapy drugs? What is their efficacy?
A: The meaning of “targeted” is that TKI can accurately target the leukemic cells of slow granules, while affecting the normal cells less, so the efficacy is better and the side effects are less.
As mentioned in Q7, 90% of patients currently treated with TKI can survive for a long time. Moreover, because of its convenience and low side effects, patients can generally work and live normally. Therefore, the current medical guidelines for the treatment of chronic granulocytes at home and abroad recommend tyrosine kinase inhibitors (TKI) as the first choice for the treatment of chronic granulocytes, and then switch to other treatment options when the efficacy is poor.
Clinical data at home and abroad have confirmed that the efficacy of the second-generation TKI drugs nilotinib and dasatinib can achieve a deeper degree of efficacy more quickly than the first-generation drug imatinib, and whether more patients can survive and discontinue the drug is the direction of future research.
Q11: Can I treat chronic granulocytic leukemia with imatinib in India?
A: Personally, I am strongly opposed to patients using Indian drugs to treat chronic granulocytes. Indian drugs are not legal to purchase and therefore not regular, more fake drugs (for example, the ingredients in it are hydroxyurea, or even just starch, etc.), so it is likely to delay the disease.
Q12: Tyrosine kinase inhibitors are currently available as first generation drugs Imatinib and second generation drugs Nilotinib and Dasatinib, how should I choose? A: Imatinib is the earliest and longest used TKI, and its efficacy has been confirmed by a large amount of clinical data. At the same time, most of the TKI’s currently in the medical insurance reimbursement list are imatinib, and second-generation drugs are only reimbursed in very few provinces. Therefore, imatinib is still used as the first choice for the initial treatment of slow particles in China.
During the treatment process, patients should focus on communication and cooperation with their doctors and standardize the medication under the guidance of their doctors, while patients should pay attention to and strictly comply with medical advice for various tests in order to accurately monitor changes in their condition.
As mentioned in Q9, the second-generation drugs nilotinib and dasatinib can achieve a deeper degree of efficacy more quickly than imatinib, potentially allowing more patients to survive and discontinue the drug. Current foreign guidelines for the treatment of slow onset granulocytes also include the second-generation drugs nilotinib, dasatinib and imatinib side by side as the drugs of choice for treatment. Therefore, if there are indicators suggesting that the patient may not be efficacious with imatinib, and the patient is in a better financial position to afford treatment with second-generation drugs, or has higher quality-of-life requirements and looks forward to increasing his or her likelihood of discontinuing the drug in the future, he or she may consider a second-generation drug as the first choice.
Q13: Are the side effects of tyrosine kinase inhibitors (TKI) significant? What are the side effects? A: TKI is a targeted drug, which can be targeted to slow granulocytes, so it has less impact on normal cells and has fewer and less severe side effects. However, a small number of patients may experience serious adverse reactions (especially at the beginning of the drug), so it is very important to monitor the side effects by conducting relevant examinations in a timely manner as prescribed by the doctor. The side effects of TKI can be divided into: A) hematological adverse reactions, i.e. decrease in white blood cells, red blood cells and platelets; B) non-hematological adverse reactions, including rash, edema, muscle cramps and cardiovascular events; C) biochemical abnormalities, including bilirubin, blood glucose, lipase, transaminases and other biochemical index abnormalities.
However, the side effects are similar but occur at different rates for different TKI.
This article is authorized by Dr. Wei-Ming Lai.