Professor Wang Jianxiang and Professor Liu Bingcheng promote the establishment of a standardized diagnosis and treatment system for CML

Introduction Chronic myeloid leukemia (CML) is a malignant disease of hematopoietic stem cells dominated by myeloid hyperplasia, with an annual incidence of (1-2)/100,000 worldwi.
Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have brought revolutionary changes to the treatment of C.
Most patients have the same survival period as normal people and may achieve functional cu.
However, some patients developed drug resistance during TKI treatment, among which point mutation of ABL kinase domain is the main mechanism leading to TKI resistance and treatment failu.
CML patients with T315I mutation are resistant to all current first- and second-generation TKI inhibito.
Resista.
In 2021, China ushered in the first third-generation TKI drug, orabatinib (trade name: Neric®), which filled the treatment gap for patients with first- and second-generation TKI resistance and T315I mutation, and opened the door A new era of precise diagnosis and treatment of C.
However, the current CML treatment still has problems such as irregular follow-up and untimely monitoring of some patients, resulting in unsatisfactory treatment outcom.
Based on this, the National Clinical Research Center of Hematology and the Alliance of Hematology Specialists intend to lead the "CML Standardized Diagnosis and Treatment Collaboration Project", which is committed to continuing to promote the standardized diagnosis and treatment of C.
The project will cover secondary and tertiary comprehensive or specialized hospitals specializing in hematology, carry out a series of lecture tours, fixed-point exchanges, establish a two-way referral mechanism, and promote the homogenization of CML diagnosis and treatme.
It will also focus on the latest guidelin.
Academic discussion on standardized diagnosis and treatment of multi-dimensional CML, including CML diagnosis and staging, CML risk stratification, CML treatment and efficacy evaluation, regular follow-up and standardized monitoring, mutation detection and precise treatment, standardized diagnosis and treatment of drug-resistant CML patients, and difficult cases Share and discu.
Interview •Professor Wang Jianxiang's Medical Pulse: Could you talk about the state's guidance on hierarchical diagnosis and treatment and the construction of specialist alliances? How can the standardized diagnosis and treatment of hematological tumors, especially CML, be promoted in combination with national policies? Professor Wang Jianxiang's national "Guiding Opinions on Promoting the Construction of a Hierarchical Diagnosis and Treatment System" advocates the establishment of medical alliances, chronic disease management, and telemedicine platforms as pilots, aiming to allocate medical resources rationally, so that high-quality medical resources can sink, so that patients who seek medical treatment can Reasonable medical channels and hospitals can better diagnose and treat patients, and avoid too many patients being concentrated in large hospitals, resulting in unequal medical resourc.
Promoting hierarchical diagnosis and treatment and ensuring medical quality is a long-term, arduous and complex systematic proje.
The establishment of specialist alliances is an important starting point for promoting hierarchical diagnosis and treatme.
Different from general hospitals, specialized hospitals treat relatively special diseases, and the requirements for diagnosis and treatment technology in different regions are not unifo.
Specialist alliance building can bridge gaps, especially knowledge ga.
Only by mastering advanced diagnosis and treatment knowledge, can we know how to better diagnosis and treatme.
Through the construction of specialist alliances, the exchange of what is necessary can ensure the curative effect of patien.
The standardized diagnosis and treatment of CML can be gradually advanced in combination with the hierarchical diagnosis and treatment system and the construction of specialist allianc.
After the targeted drugs are launched, the prognosis of CML patients has improved, from a fatal disease with a survival period of only about three years to a chronic disease that can be controll.
In addition, the second and third generation targeted drugs have overcome the drug resistance that occurred during the treatment of C.
Or in the case of intolerance, the survival period of patients is greatly prolonged, the management cycle is significantly longer, the number of accumulated patients is significantly increased, and the requirements for the energy, manpower, material resources and even the hospital invested in management are getting higher and high.
The management of patients in large national medical centers leads to insufficient medical resourc.
Therefore, in the long life cycle management of CML, it is necessary to cooperate with different levels and different types of medical institutions in the construction of the hierarchical diagnosis and treatment system and the construction of the specialist allian.
Yimaitong: Could you please talk about what activities will be carried out by the National Hematology Clinical Medical Research Center and the Hematology Specialist Alliance in the standardized management and two-way referral of CML in cooperation with hospitals at all levels? Professor Wang Jianxiang's CML treatment drugs continue to develop, and more and more patients benefit from them, but they still face intolerance, drug resistance, treatment progress, and drug withdrawal during the treatment proce.
In order to ensure the curative effect, the CML diagnosis and treatment guidelines will be continuously updated and enriched based on a large number of clinical studies at home and abroad, such as guiding patient management through cytogenetics or molecular respons.
Therefore, learning the latest guidelines and passing the most advanced standardized treatment concepts and management concepts of CML to domestic doctors is a must-have activi.
CML is easily confused with other diseases, and large medical centers in the country and regions shoulder the responsibility of screening patien.
Accurately diagnosing patients and giving treatment recommendations is the main responsibility of large medical centers, and the lengthy treatment process should be completed by medical institutions at different leve.
In order to ensure curative effect, large medical centers need to guide medical institutions at different levels to monitor patients, evaluate curative effects, and adjust treatment pla.
In addition, for the chronic disease management of CML, it is particularly important to carry out specialist alliance activities such as mutual diagnosis, two-way referral, and multi-direction referr.
The development of standardized diagnosis and treatment projects for CML will successfully turn malignant diseases into controllable chronic diseas.

Equalizing the medical resources of medical institutions at different levels by means of specialist alliances, so as to effectively control CML, is a long-term project, and there is still a lot of work to be do.
Yimaitong: What do you think are the characteristics of this CML standardized diagnosis and treatment project, and what kind of help can it bring to CML patients in my country? Professor Wang Jianxiang passed the CML standardized management concept to domestic doctors, and did a good job in guiding the work, and gradually formed a hierarchical diagnosis and treatment model of "two-way referral, upper and lower linkage", which is an important feature and responsibility of the CML standardized diagnosis and treatment proje.

Completing the management of CML patients in different diagnosis and treatment hospitals can enable patients to receive effective treatment in their territories, and save the trouble of traveling long distances to see a large central hospit.

Especially under the special circumstances of epidemic prevention and control in recent years, it is difficult to go out to seek medical treatme.

If you can seek medical treatment nearby under the guidance of the principle of graded medical treatment, it is a major event that benefits the country and the peop.

Therefore, the implementation of the CML standardized diagnosis and treatment project enables patients to be assured of local treatment and monitoring, which can not only achieve the same or even better curative effect, but also reduce the burden on patien.

Yimaitong: The latest domestic guidelines have updated the treatment regimens for CML patients with T315I resistance and Philadelphia chromosome-positive acute lymphoblastic leukemia patients, including the third-generation TKI drug orebatinib, which you think will bring clinical benefits to the clin.

Which benefits? Professor Wang Jianxiang CML is a dynamic disease that, if poorly controlled, can lead to treatment failure or disease progressi.

The T315I mutation is resistant to a variety of first- and second-generation TKI drugs, which is one of the problems of treatment failure in CML patien.

The third generation of TKI drugs can effectively overcome drug resistan.

Orebatinib is a third-generation TKI drug independently developed in Chi.

Preclinical in vitro and in vivo studies and clinical studies have confirmed that it is effective in patients with T315I mutation resistance, and even in blastic CML patien.

Therefore, orebatinib alone or in combination with other drugs can be used as an effective treatment for patients with T315I-mutated CML in chronic phase, accelerated phase or blast phase, and more and more refractory patients are expected to be "cure.
Interview •Professor Liu Bingcheng Yimaitong: CML has entered the era of chronic disease manageme.

Could you please talk about the key points that need attention in the clinical practice of standardized diagnosis and treatment of CML? Professor Liu Bingcheng With the application of TKI, CML has transformed from a proliferative malignant tumor to a chronic disease with long-term survival close to healthy people, and the management of chronic disease in the later stage is particularly importa.

In the era of chronic disease management of CML, there are many key nodes in the clinic that need to be paid attention by doctors and patien.

The diversification of treatment options and the continuous evolution of treatment goals make the choice of initial treatment drugs very critic.

From the perspective of clinicians, the clinical practice of standardized diagnosis and treatment of CML needs to consider three aspects: First, when determining the initial treatment plan, we should not only be satisfied with the diagnosis of CML, but also clarify its specific disease stage and prognosis stratificati.

Disease stage is the most important factor in determining prognos.

Prognostic stratification can predict the treatment response of patients to first- and second-generation TKI drugs, which is helpful for clinicians to make the best treatment choic.

In addition, cytogenetic and molecular factors can also affect a patient's response to TKI therapy, so a comprehensive cytogenetic and molecular investigation should be performed before initiation of thera.

Second, treatment goals need to be determined before initial treatment is initiated, and treatment goals drive the selection and replacement of therapeutic dru.

At present, the treatment goal of CML has changed from prolonging survival to pursuing treatment-free remissi.

However, no treatment remission is closely related to early treatment response, and the results of early treatment response to different drugs are not the sa.

Drug selection should be based on treatment goa.

Third, different patients have different drug tolerances, and CML mostly occurs in middle-aged and elderly peop.

Patients may be complicated by other diseas.

Comorbid diseases involving drug metabolism-related organs and the use of comorbidities may affect the efficacy of CML treatment dru.

Therefore, The patient's tolerance and comorbidities need to be considered when choosing a drug
The determination of the first-line treatment plan means that most of the diagnosis and treatment of CML has been completed, and the later chronic disease management needs to adjust the treatment strategy in time according to the treatment respon.

In addition, the success of CML treatment is inseparable from the cooperation of patien.

Patient compliance includes two aspects: compliance with continuous drug treatment and compliance with monitoring, which complement and complement each oth.

Adherence depends on the patient's understanding of the disease and the treatment of adverse drug reactions by clinicia.

Therefore, improving patients' disease cognition and actively dealing with patients' adverse drug reactions are effective measures to improve patients' medication complian.

In addition, after the patient's disease is under control, their mental health also needs the joint attention of doctors, relatives, friends, colleagues and other parties, so that the patient can return to a normal life and establish a normal social relationship, which also has a very positive impact on the patient's treatme.

Yimaitong: Do you think that the irregular follow-up and untimely monitoring of CML patients in primary hospitals are an important cause of disease progression? What needs to be improved? Professor Liu Bingcheng, whether in primary hospitals or large medical centers, may cause irregular follow-up and untimely monitoring of patients due to various reaso.

Poor compliance is an important reason for irregular follow-up and untimely monitoring, which will further lead to the failure of clinicians to identify poor prognosis as early as possible, leading to disease progressi.

To improve the problems of irregular follow-up and untimely monitoring of CML patients, it is necessary to carry out patient education and doctor education at the same ti.

On the one hand, improving patients' awareness of the disease and making them understand that the efficacy evaluation of CML is not limited to hematological responses or CML symptoms, but should further evaluate cytogenetic and molecular responses; on the other hand, monitoring conditions in primary hospitals are limit.

Referral services should be provided in the case of CML; in addition, guideline lectures should be carried out regularly, so that hematologists or physicians who are not familiar with CML can regularly learn and communicate with each oth.
Yimaitong: In the standard path of CML standard diagnosis and treatment, will corresponding adjustments be made according to the latest domestic guidelines for patients with T315I mutation and drug resistance, so as to improve the whole process of CML standardization? With the progress of treatment, monitoring methods and treatment goals, Professor Liu Bingcheng has continuously updated domestic and foreign guidelin.

Guidelines are the summarization and summarization of a large number of clinical practices that follow large-scale evidence-based medical evidence, and each edition of the guidelines needs to be read and thoroughly re.

Since there were no third-generation TKI drugs available in China in the past, the "Chinese Guidelines for Diagnosis and Treatment of Chronic Myeloid Leukemia (2020 Edition)" did not mention mu.

The launch of orebatinib meets the treatment needs of patients with CML with T315I mutation in the chronic phase or accelerated pha.

The "2022 CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies" specifically elaborated on the issues of T315I mutation and drug resistan.

Therefore, early identification of CML patients with chronic or accelerated CML who may carry T315I and timely adjustment of their treatment strategies have become a very important part of improving the whole process of CML specificati.

Yimaitong: Combined with this domestic guideline update, how do you think the third-generation TKIs can help fill the clinical gap? Pr.

Liu Bingcheng's latest CSCO guideline combines the clinical indications of orebatinib, which is expected to fill the unmet clinical needs of patients with T315I mutation in the chronic phase or accelerated phase of C.

Orebatinib can also be widely used in clinical practi.

applicati.

At present, after the first- and second-generation TKI drugs are widely used in China, some patients develop intolerance or drug resistance or even disease progression, but no T315I mutation occu.

Can such patients be treated with third-generation drugs? For patients with poor response to early treatment, especially for patients with poor response to first- and second-generation TKIs, continuous clinical exploration and practice are requir.
Professor Wang Jianxiang Director of National Hematology Clinical Research Center, Hematology Hospital, Chinese Academy of Medical Sciences Former Director of Hematology Branch of Chinese Medical Association Vice President of Internal Medicine Branch of Chinese Medical Doctor Association Vice President of Hematology Branch of Chinese Medical Doctor Association Deputy Editor-in-Chief J Hematol & Oncol Blood editor-in-chief editor-in-chief of Chinese Journal of Hematology (2012-2016) Chairman of Hematology and Oncology Committee of China Anti-Cancer Association (2012-2015) "Outstanding Youth", "New Century Hundred Thousand Talents Project" National Candidate, Ministry of Health Outstanding Tribute expert, State Council special sticker expert CD19, CD33 CAR-T main developer of leukemia treatment leader, prognosis stratification, intensive induction, whole process management, significantly improved the efficacy of acute leukemia, led the formulation of "Acute Myeloid Leukemia", "Acute Myeloid Leukemia" "Lymphocytic Leukemia" and "Chronic Myeloid Leukemia" Diagnosis and Treatment Guidelines NIH Postdoctoral Outstanding Research Award, the first prize of the 10th "Wu Jieping Medical Research Award - Paul Janssen Pharmaceutical Research Award", the first prize of Tianjin Science and Technology Progress Award (The first person to complete) Professor Liu Bingcheng, Chinese Academy of Medical Sciences Hematology Hospital, Chinese Academy of Medical Sciences, Chief Physician, MD, Member of the Standing Committee of the Leukemia Branch of the Chinese Medical Education Association, Member of the Chinese Charity Association Patient Assistance Project Hematology Special Committee Member who has been engaged in hematological diseases for a long time Clinical and research work, especially the diagnosis and treatment of acute leukemia and myeloid tumors, has rich experience in the long-term management of CML patien.

Presided over and participated in a number of national and provincial scientific research projec.

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