I. How to detect CML early?
Many patients with CML are found to have elevated white blood cells due to routine blood tests for other reasons, or routine physical examinations. The diagnosis of CML is made after hematologic bone marrow morphology, chromosomes, and BCR/ABL1 fusion gene, and some patients have symptoms such as malaise, weight loss, low-grade fever, abdominal masses, etc. They go to the hospital and find abnormally elevated white blood cells, and CML is found after further examination. It is often possible to detect blood abnormalities and seek early diagnosis.
Criteria for CML diagnosis
CML often has typical clinical manifestations, including abnormally elevated white blood cells, elevated eosinophils, splenomegaly, and abnormally active bone marrow proliferation. The specific diagnostic criteria are a positive Philadelphia chromosome (Ph) and a positive BCR/ABL1 fusion gene, which are necessary for the diagnosis of CML. A small number of patients have typical CML but are negative for the Ph chromosome or BCR/ABL1 fusion gene. variability exists in the Ph chromosome and BCR/ABL1 gene, and variant CML can be detected by FISH or BCR/ABL1 gene screening. variant CML remains effective against targeted drugs TKI-like drugs. In contrast, patients without Ph chromosome and BCR/ABL1 gene are to be excluded from the diagnosis of CML, and MPN diagnosis such as atypical slow granulation is considered, and the corresponding treatment principles are completely different.
Third, what should I do if I have been diagnosed with CML?
For patients who have just been diagnosed with CML, it often feels like the sky is falling. “Leukemia”, what a terrible and unfamiliar term. Many family members choose not to tell the patient about the diagnosis for the time being; CML, especially in the chronic stage, is a relatively mild disease that does not progress as aggressively as acute leukemia, and many patients may only need outpatient treatment. CML is one of the most effective types of leukemia due to the availability of targeted drugs and the best results with allogeneic transplants. Once CML is diagnosed, it needs to be treated as soon as possible. If available, targeted drugs such as imatinib should be applied as soon as possible. In addition, CML requires long-term regular medication and regular follow-up so that the treatment plan can be adjusted when appropriate.
Fourth, the choice of drug treatment for CML
When it comes to the treatment of CML, the first thing that needs to be clarified is the stage of the disease. The natural course of CML is divided into three phases: chronic phase, accelerated phase, and acute phase. The vast majority of patients are in the chronic phase when CML is first diagnosed, about 20% of patients are already in the accelerated phase when they are diagnosed with chronic granules, and very few patients are already in the acute phase when they are found.
(i) Drug therapy in the chronic phase
The preferred choice is the complex amino acid kinase inhibitor (TKI) imatinib, also known as Gleevec. For patients who have financial difficulties and cannot afford Gleevec treatment, the alternative treatment is interferon. Chemotherapy drugs such as hydroxyurea are mostly used at the beginning of the disease to reduce the high white blood cell load.
Imatinib: Launched in China in 2001, it has become the first-line treatment for slow-onset particles. 400/day in the chronic phase.
The famous IRIS study, for newly diagnosed CML, has an 8-year overall survival rate of 85%. The golden indicator to assess prognosis is also cytogenetic examination. It should be reminded here that the health insurance genetic examination as the gold indicator for efficacy assessment refers to chromosomal examination of G bands, not FISH. in the last two years, genetic examination, the results of BCR/ABL quantification are getting more and more attention, and the examination of genetic quantification at 3 months and 6 months of Gleevec treatment <10% ready to be considered as an important indicator of early prognosis to guide patients to change their treatment strategy early.
Second-generation TKI drugs: nilotinib and dasatinib have been incorporated into the first-line treatment of primary CML in Europe and the United States. Current Chinese CML guidelines still place second-generation drugs in the second-line treatment position. They are often used for CML where the effect of griseofulvin is not satisfactory.
Interferon has been used in CML since 1980 and became the first-line treatment for patients with CML-CP after 1990. after 2000, its first-line position was replaced by Gleevec. However, it is still widely used for patients with funding difficulties, Gleevec intolerance, pregnancy, etc. Chinese CML guidelines, still place it as first-line treatment. The median survival rates for low-risk, intermediate-risk, and high-risk chronic-phase CML are 98 months, 65 months, and 42 months, respectively. This did result in significantly longer survival in a subset of patients compared to conventional hydroxyurea and chemotherapy. The most important prognostic indicator of interferon therapy is the cytogenetic response, that is, the absence or disappearance of the Ph chromosome. Interferon is poorly effective in patients who progress to the accelerated and acute stages.
Hydroxyurea Used in the clinic in the 1960s, it was once the first-line treatment for CML. Currently, it is only used as an adjuvant therapy during the early stages of the disease, during hyperleukocytosis.
Chemotherapy Patients with chronic phase, unless Imatinib and other treatments are ineffective, are generally not recommended.
(ii) Treatment of accelerated and acute phase
TKI For patients whose disease has not been treated with gleevec-based drugs, TKI-based drugs are preferred: imatinib, nilotinib and dasatinib. For patients with disease progression during the application of TKI-like drugs, TKI resistance mutations need to be done to screen for potentially effective TKI drugs.
Combination chemotherapy : High trichostatin has been used in China since the last century 70, mostly for progressive treatment. For patients who are resistant to interferon or 5 or griseofulvin, the combination can improve the efficacy. It is effective for patients with T315I mutation due to different mechanism of action. It is inexpensive and safe to apply. For CML entering the acute phase, the appropriate chemotherapy regimen is selected for treatment according to whether it is an AML or ALL mutation.
V. HSCT
Allogeneic transplantation has been used for the treatment of CML since 1973 and has become the only means of complete cure. As transplantation techniques have improved and supportive therapy has been enhanced, outcomes have improved. Outcomes vary widely from one transplant center to another.
Indications for transplantation of chronic granulocytes
1. Progressive chronic granulocytes, the only way to transplant as soon as conditions are available and the disease is under control. The donor can be chosen from sibling compatible, non-blood compatible, semi-identical donors.
2, chronic phase drug effect is not good
The IRIS study has an 8-year long-term overall survival rate of 85% for patients in the chronic phase of chronic granulocytes. The IRIS study had an 8-year long-term overall survival rate of 85%, while the Dopey team had a 90% long-term survival rate for sibling-identical transplants and an 85% overall survival rate for non-blood-identical donors in the chronic phase. International guidelines in Europe and the United States are for first- or second-line TKI. allogeneic transplantation is placed in the second- or even third-line position. In the context of the Chinese situation, Chinese CML guidelines still place allogeneic transplantation in the first-line position. However, for CML-CP patients with good efficacy of Gleevec, hemaphase transplantation is not advocated.
3. Pediatric slow-onset granules