1.Why should chronic granulocytic leukemia be medicated as soon as possible after diagnosis?
A: Chronic granulocytic leukemia is divided into chronic phase (early), accelerated phase (middle) and acute phase (late).
Fortunately, most patients are in the early stage when they are diagnosed with chronic granulocytic leukemia, and clinical data at home and abroad confirm that early medication has the best effect and can better control the disease. If they enter the accelerated or even acute phase, the biological characteristics of leukemia have changed, making it more difficult to treat and to achieve better results with medication.
In addition, some patients in the chronic phase, even without special drugs, may not experience serious symptoms for 2-3 years and feel good about themselves, so they are unwilling to take tyrosine kinase inhibitors (TKI) and other drugs with better efficacy but relatively high prices; or they may take TKI drugs at the beginning 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, when it is difficult to achieve satisfactory results with drugs.
2.Can chronic granulocytic leukemia be cured?
A: This question cannot be answered simply as to whether it can or cannot.
For the same individual, different doctors will use different treatments according to their clinical experience, and different treatments have different “cure” ratios, and of course different risks of failure.
The same treatment may also produce different results for different individuals.
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 the best cure for chronic granulocytosis, with a cure rate of about 80% for patients in the chronic phase.
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 has to 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.
One more treatment modality, which is currently the most widely used, is treatment with tyrosine kinase inhibitors (TKI) (its generation of drugs is imatinib, the second generation of drugs are nilotinib and dasatinib, while three generations of drugs have been marketed 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 treatments such as interferon, cytarabine or hydroxyurea are basically not very effective for chronic granulocytic leukemia.
3. 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 from 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 similar to 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 will survive for a long time.
4.After the diagnosis of chronic granulocytic leukemia, is it necessary to use tyrosine kinase inhibitors (Imatinib, Nilotinib, Dasatinib and other drugs)?
A: As stated in Q3, Ph chromosome translocation is the underlying cause of the pathogenesis of slow granulocytosis, and the resulting BCR/ABL fusion gene, which encodes a protein causing enhanced tyrosine kinase activity, is the pathogenesis of slow 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.
At present, 90% of patients treated with TKI can survive for a long time; and because it is easy to take and has fewer 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.
5.If I cannot afford the cost of TKI treatment, are there other ways to treat LRD?
A: First of all, bone marrow transplantation is an option with a high probability of curing lp, but because of certain prerequisites, such as the need for a matched donor, the high cost, and the existence of serious complications, transplantation is currently used as a second-line treatment option only when TKI is ineffective.
More powerful second-generation drugs nilotinib and dasatinib are also available. 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 lower elevated white blood cells, normalize blood count, shrink the spleen, and achieve some superficial efficacy. However, as mentioned before, chronic 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 special 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 these will undoubtedly help patients to choose to receive TKI treatment.
6.Why are tyrosine kinase inhibitors (Imatinib, Nilotinib, Dasatinib and other drugs) 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 above, 90% of the patients treated with TKI can survive for a long time. In addition, 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.
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 stop the drug is the direction of future research.
7.Tyrosine kinase inhibitors currently have a generation of drugs imatinib, second-generation drugs are nilotinib and dasatinib, how to choose?
A: Imatinib is the earliest and longest used TKI, and a large amount of clinical data has confirmed its efficacy. 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. At the same time, patients should pay attention to and strictly comply with medical advice for various examinations in order to accurately monitor changes in their conditions.
The second-generation drugs nilotinib and dasatinib can achieve a deeper degree of efficacy more quickly than imatinib, potentially enabling 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 as the drugs of choice for treatment. Therefore, if there are indicators suggesting that patients may not be as effective with imatinib and they are in a better financial position to afford treatment with second-generation drugs, or they have higher quality of life requirements and are looking forward to increasing their likelihood of discontinuing the drug in the future, they may consider second-generation drugs as their first choice.