2022 SHS Miao Aiming Director: Focus on prevention, traceability, and curative effect, and the treatment level of aplastic anemia will be raised to a higher level

Aplastic anemia (AA) is an acquired bone marrow hematopoietic failure disease whose main clinical manifestations are anemia, infection and bleeding
.
With the continuous progress of immunosuppressive therapy and hematopoietic stem cell transplantation (HSCT), the efficacy of AA has improved
.
However, due to the current sibling HSCT limited by the patient's age, physical status, donor source, and treatment-related risks, most patients eventually receive immunosuppressive therapy
.
However, the hematological complete response rate of immunosuppressive therapy is not high, and the treatment need for AA remains unmet
.
At the "2022 Suzhou Hematology Summit and National Continuing Medical Education Class" held in Suzhou on October 7-9, 2022, Yimaitong specially invited the director of the First Affiliated Hospital of Soochow University to be interviewed to share the clinical treatment status of AA and look forward
to the future treatment of AA.

AA is an acquired hematopoietic stem cell disease mediated by the immune system, manifested by myeloid cells and pancytopenia
.
What is the current status of AA treatment? What are the unmet treatment needs?

From the perspective of the global incidence of AA, the incidence of AA in Asia, especially in China, is high
.
There are two age peaks in the onset of AA, the adolescent stage and the old age stage
.
Treatment needs vary for AA patients of different ages
.
For young patients with AA, the goal of treatment is long-term disease-free survival
.
The overall efficacy of elderly AA patients is relatively poor, and for elderly AA patients, the goal of treatment is to improve the quality of life and prolong the life of
patients.

At present, there are two main treatment strategies for AA, one of which is HSCT, and sibling holographic HSCT is the most effective treatment for
AA.
However, the HLA full compatibility rate between siblings is not high, so there is a problem
of limited donor sources.
In recent years, researchers around the world have been exploring alternative donor HSCT technology
.
Alternative donor HSCT includes inter-related haploid HSCT, unrelated donor HSCT, etc
.
At present, the research data of haploid HSCT "Beijing protocol" and "Suzhou model" in AA treatment are constantly being updated
.
The second is immunosuppressive therapy, but immunosuppressive therapy may lead to late complications (mainly clonal disease), and some patients relapse after treatment, especially if the cyclosporine reduction regimen is inadequate, which can increase the risk of
AA recurrence.
In recent years, TPO receptor agonists have been gradually applied to AA, making up for the shortcomings
of cyclosporine monotherapy in AA treatment.

From the latest global data and Chinese data, for young AA patients, especially < 20-year-old patients, the efficacy of alternative donor HSCT is also close to that of sibling total HSCT; Patients without a sibling full donor who are assessed to be immunosuppressive are selected for immunosuppressive therapy
.
Elderly AA has clinical features
such as high risk of infection and bleeding, and poor treatment tolerance.
Therefore, for elderly AA patients, immunosuppressive therapy is still the mainstay
.
However, at present, some patients with AA can neither tolerate immunosuppressive therapy nor have suitable donors for HSCT, and further exploration
is needed for the treatment of such patients.

Overall, the future exploration directions of AA treatment include: how to further reduce the pretreatment toxicity of HSCT in AA patients, reduce treatment-related mortality, reduce the occurrence of graft-versus-host disease (GVHD), and reduce GVHD
.

Yimaitong: What are the treatment progress worth paying attention to in the field of AA in recent years?

Interesting therapeutic advances in the field of AA include two aspects, one of which is new drugs, such as TPO receptor agonists, which can be combined with immunosuppressive therapy to improve the hematological response rate
of AA patients.
The second is HSCT, and the current haploid HSCT "Beijing scheme" and "Suzhou model" have shown preliminary efficacy
in AA.
The transplant team of the First Affiliated Hospital of Soochow University also conducted a study to evaluate the long-term quality of life of patients receiving haploid HSCT, and published the results in international journals, which received extensive attention
at home and abroad.

At present, AA-related new drug research is less common than lymphoma and multiple myeloma, but new drugs are also being used in
AA.
The exploration of the pathogenesis of AA, especially the pathogenesis of Treg cells and NK cells, may be the direction
of exploration of AA treatment in the future.

Yimaitong: What do you think is the status of haploid hematopoietic stem cell transplantation in severe AA?

At present, haploid HSCT in AA is still developing, and there is still a lack of data from relevant prospective randomized controlled studies, so it has not been included in the first-line treatment of
AA.
However, many medical centers have begun to explore the use of haploid HSCT in the first-line treatment of AA, aiming to screen out the types
of AA patients suitable for first-line HSCT.
In addition, medical centers have begun to explore the use of non-HSCT treatment in AA, with the aim of screening out the types of
patients who can benefit from non-HSCT methods.

CareConnect: Can you tell us about your outlook for AA treatment in the future?

The prospect of future AA treatment mainly covers two aspects, one is the prevention of AA, the future should pay attention to the prevention of AA, especially the prevention of AA in adolescents, according to the possible causes of AA, such as chemical poisons, environmental pollution, etc.
, as far as possible from the root cause of the disease
.
Second, the treatment of AA, how to reduce the toxicity of AA treatment, improve the recovery ability of patients' hematopoietic function, and reduce the occurrence of complications in treatment, etc.
, are all urgent issues
that need to be explored in the future of AA treatment.
In addition, there are many problems
that need to be explored and solved in AA haploid HSCT.

Director Miao

• Chief Physician, The First Affiliated Hospital of Soochow University

• Member of the Red Cell Disease Group of the Hematology Branch of the Chinese Medical Association

• Member of Hematology Branch of Chinese Geriatrics Society

• Vice Chairman of the MDS Academic Working Committee of the Hematology Branch of the Chinese Geriatrics Association

• Vice Chairman of the Red Blood Cell Disease Working Group of the Hematology Branch of the Chinese Geriatrics Society

• Member of the Expert Committee of China MDS/MPN Working Group

• Deputy head of the red blood cell disease group of the Hematology Branch of Jiangsu Medical Association

• Subspecialty specialty: diagnosis and treatment of red blood cell diseases, myeloproliferative diseases and hematopoietic stem cell transplantation treatment technology