2022CSH Professor Zhang Xi: Over the lofty mountains, willow dark flowers, a number of guidelines were released, in-depth analysis of GVHD precision prevention and control strategies

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treatment of a variety of blood system diseases, and the success of haplo-type hematopoietic stem cell transplantation (haplo-HSCT) has led to a rapid increase
in the number of hematopoietic stem cell transplantation cases in China.
According to the report of the Chinese Hematopoietic Stem Cell Transplantation Registration Group, in 2019, 140 companies in China implemented nearly 10,000 cases of allo-HSCT, of which haplo-HSCT accounted for 60%.

Despite the continuous improvement in the efficacy of allo-HSCT, graft-versus-host disease (GVHD) remains the leading comorbidity and cause
of death.

On September 23-25, 2022, the 17th National Hematology Academic Conference of the Chinese Medical Association was grandly opened
at the National Exhibition and Convention Center in Shanghai.
The conference was hosted by the Chinese Medical Association and the Hematology Branch of the Chinese Medical Association, hosted by the Shanghai Medical Association, co-organized by Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, the First Affiliated Hospital of Soochow University, and the Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, with the theme of "respect, inheritance, collaboration and innovation", specially invited famous experts at home and abroad to talk about the latest progress
in the field of blood diseases.
On this occasion, Professor Zhang Xi of Xinqiao Hospital of Army Military Medical University was specially invited to interpret the current situation, latest progress and future development of GVHD prevention and treatment for the readers!

Medical Pulse Pass: The 2022 China Hematopoietic Stem Cell Transplantation (HSCT) Academic Conference shows that the Hematopoietic Stem Cell Application Group of the Hematology Branch of the Chinese Medical Association has issued a total of 12 consensuses, and your team has written the GVHD-related consensus, can you please introduce the content of the consensus for us?

In the past year, with the support of Chairman Wu Depei, Professor Huang Xiaojun and Professor Hu Yu, and under the specific organization of Professor Zhang Xiaohui, the leader of the Hematopoietic Stem Cell Application Group, and many other leading figures in hematology, the consensus compilation of the study group guidelines has achieved fruitful results
.
As the main author of "Chronic Graft-versus-Host Disease (cGVHD) China Expert Consensus (2021 Edition)", I have two feelings:

First, as a major complication after transplantation, the incidence of cGVHD is getting higher and higher
.
With the maturity of transplantation technology, more and more patients have obtained better survival, in this process, patients have higher and higher requirements for quality of life, cGVHD is precisely a disease
that causes a serious decline in the quality of life of patients.
In addition, China's haplo-HSCT ratio is high, and the incidence of cGVHD after transplantation is higher than that of full-phase transplantation, and there is an urgent need to form a consensus to standardize diagnosis and treatment
.
Therefore, the hematopoietic stem cell application group wrote China's first cGVHD expert consensus, and formed corresponding expert recommendations on the pathogenesis, diagnostic criteria, first-line treatment and second-line treatment of cGVHD, which played a great role
in the management of cGVHD by clinicians.

Second, this press conference launched a new expert consensus preparation for
the eye GVHD.
The eye is an important part of GVHD, once there is a rejection reaction, the light has dry eyes, that is, dry eye, and the heavy affects vision, and even blindness, which seriously affects the patient's quality of
life.
However, so far, the treatment of ocular GVHD is still lacking in standardization and requires multidisciplinary joint diagnosis and treatment, so it is urgent to cooperate with ophthalmologists to improve and standardize the diagnosis and treatment
of GVHD of such fine organs.
So far, the work of the transcript has been basically completed, and the next step will be to start the joint discussion and revision of transplant experts in the academic group and strive to complete
it within this year.

Doctor Pulse Pass: GVHD can seriously endanger life, hematopoietic stem cell application group has done a lot of work on this, can you please talk about the prevention and treatment of GVHD after allo-HSCT, share what specific work plans the hematopoietic stem cell application group and your team have?

GVHD is a post-transplant rejection reaction and is considered one of the three mountains in the field of transplantation
.
For leukemia patients, severe infection, disease recurrence, GVHD seriously affect the patient's quality of life and even life after transplantation, clinicians vividly call it the three mountains, to do a good job of transplantation, and eventually have to face and cross these three mountains
.
GVHD is a fatal post-transplant complication, and in the treatment of GVHD, there are basically two strategies
for prevention and treatment.

In terms of prevention, the prevention of GVHD has Chinese characteristics, such as in haploid transplantation, the Chinese-based GVHD prevention and control technology based on granulocyte colony-stimulating factor (G-CSF) and antithymic globulin (ATG) - the "Beijing Scheme" has been verified by many cases and can well control GVHD after haplo-HSCT; The Army Military Medical University Shimboji Hospital Hematology Medical Center used mesenchymal stem cells to prevent the occurrence of cGVHD, and achieved certain results, which were published in the journal JCO; Peking University People's Hospital is exploring the combination of reduced doses of ATG or ATG and small doses of cyclophosphamide (PTCy) to reduce GVHD after haploid transplantation, and has also achieved good clinical research results
.
Therefore, in terms of prevention, transplant experts in China are actively working for the prevention of GVHD, which is believed to benefit
more patients.

In terms of treatment, it is first necessary to pay attention to the standardization of conventional treatment, especially first-line treatment
.
At present, whether it is acute graft-versus-host disease (aGVHD) or cGVHD, hormone-based first-line treatment options still occupy an important position, so the standardized use of hormones and the evaluation of efficacy after hormone use need to be paid attention to
.
If first-line therapy is ineffective and the disease progresses, second-line therapy
is initiated.
Clinical experience and research data show that mesenchymal stem cells have a good effect
in the treatment of GVHD.
In the past, severe GVHD threatened the lives of patients, with the emergence of new drugs such as sirolimus, JAK2 inhibitor rucotinib, CD20 monoclonal antibody, TNFα monoclonal antibody and other new drugs, refractory and poor hormone therapy effect of GVHD has been better controlled
.

In addition, after GVHD is effectively controlled, long-term observation and follow-up also need to be further regulated
.
At present, there are still patients with GVHD who reduce and discontinue drugs after disease control
.
Therefore, it is necessary to bring conceptual innovation to patients and their families through patient education, so that patients can standardize medication
.

Finally, accurate diagnosis is equally important, as early prediction and early intervention can reduce the incidence
of severe and fatal GVHD.
In terms of accurate diagnosis, it is not enough
to analyze symptoms and pathology.
At present, new research has begun to explore in depth, among which biomarkers including lymphocyte subsets, cytokines, chemokines, autoantibodies, and microRNAs are one of the research trends in the accurate diagnosis of
GVHD.
In addition, the relevant research on prognostic evaluation has also been launched, and it is believed that in the future, the clinic can diagnose and evaluate GVHD more accurately, so as to accurately use drugs, which will greatly improve
the entire GVHD field.

Professor Zhang Xi

• Chief physician, professor, postdoctoral supervisor; Distinguished Professor of Changjiang Scholars

• Director of the Hematology Medical Center of the Army Military Medical University Xinqiao Hospital

• Director of the Blood Disease Center of the People's Liberation Army of the Chinese

• Vice Chairman of China Hematology Specialty Alliance

• Standing Committee Member of Hematology Branch of Chinese Medical Association and Deputy Leader of Hematopoietic Stem Cell Application Group

• Vice Chairman of the Hematology and Oncology Committee of the Chinese Anti-Cancer Association

• He is a member of the Standing Committee of the Hematology Branch of the Chinese Medical Doctor Association

• Standing Committee Member of Experimental Hematology Committee of Chinese Society of Pathophysiology

• Chairman of the 5th and 6th Chongqing Medical Association Hematology Committee

• Presided over 39 national, provincial and ministerial projects; 92 SCI papers, up to IF 50.
  15; 5 editors/associate editors; The first person to complete the project won 1 second prize of the National Science and Technology Progress Award, 1 first prize of the Chinese Medical Science and Technology Award, and 1 second prize of the Chongqing Municipal Science and Technology Progress Award; Wrote 6 industry guides and co-edited 29 items; Won 32 national invention patents

• He has won the China Cancer Young Scientist Award, the Army's Outstanding Scientific and Technological Personnel Pacesetter, the Chongqing Chief Expert Studio and the Chongqing Municipal Innovation Group Leading Expert, the Chongqing Chief Medical Expert, the Chongqing Municipal Science and Technology Innovation Leading Talent, the Tianfu Scholar Distinguished Expert, the Army's Top Talent, and the First Batch of Army Science and Technology Talents; Editorial board and reviewer for The Lancet, JHO, Leukemia, Lancet Hematology, Science Bulletin, CMJ and other magazines

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