Professor Zhang Xi: Maintenance Therapy after AML/MDS Hematopoietic Stem Cell Transplantation The 16th National Leukemia and Lymphoma Conference

Sponsored by the Chinese Medical Association, Hematology Branch of Chinese Medical Association, Leukemia and Lymphoma Group of Hematology Branch of Chinese Medical Association, Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences), First Affiliated Hospital of University of Science and Technology of China The 16th National Leukemia and Lymphoma Academic Conference hosted by the Chinese Medical Association will be held in Hefei, Anhui Province on October 8-10, 2021
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At this conference, Professor Zhang Xi from the Second Affiliated Hospital of the Army Military Medical University conducted the topic of "Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Maintenance Treatment after Hematopoietic Stem Cell Transplantation (Epigenetic Regulation)" In the report, Yimaitong organizes the main contents as follows
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At present, the proportion of AML/MDS patients receiving hematopoietic stem cell transplantation (HSCT) is gradually increasing.
About 35% of the patients receiving HSCT in China are AML/MDS patients
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Professor Zhang Xi said that the emergence of the "Beijing Plan" has significantly improved the source of HSCT donors, and the management of graft-versus-host disease (GVHD) is no longer a thorny problem.
The main problem facing HSCT is the post-HSCT.
The recurrence of AML/MDS is also the main cause of death in AML/MDS patients after HSCT
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After HSCT, reasonable immune control is required to avoid patient recurrence and improve the efficiency of HSCT
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 Professor Zhang Xi then introduced the basic principles of epigenetic regulation applied to HSCT
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Epigenetic changes can lead to the transcriptional inhibition of tumor suppressor genes and induce apoptosis and differentiation genes; the modification of chromatin by epigenetic regulation is reversible; epigenetics such as azacitidine and decitabine Drug treatment has immunomodulatory function
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The regulation of epigenetics after HSCT is divided into three parts: maintenance treatment, preemptive treatment and salvage treatment
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Professor Zhang Xi said that the timing of epigenetic regulation after HSCT should be as early as possible in order to obtain a better curative effect and avoid the patient's disease recurrence
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Post-HSCT maintenance treatment strategy Professor Zhang Xi said that the ideal maintenance treatment option should have good anti-tumor activity and accessibility, have a positive impact on donor cells, increase the immunogenicity of malignant tumor cells, and be free of bone marrow toxicity.
, Early medication after HSCT
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Epigenetics drugs are the ideal maintenance therapy drugs after HSCT.
Related studies have shown that the use of demethylating drug (HMA) azacitidine for maintenance therapy after HSCT can effectively reduce the risk of GVHD in patients while retaining graft resistance.
Leukemia (GVL) effect, prolong the survival of patients
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Decitabine is also a better maintenance treatment option after HSCT.
A number of studies have shown that it can improve the prognosis of patients after HSCT
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However, in related studies, the dosage of decitabine in maintenance treatment after HSCT is different.
Therefore, a phase I study explored the dosage selection of decitabine in maintenance treatment after HSCT.
The average maintenance dose is 7mg/m2/day
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 The combination of HMA and other drugs can also be used as a maintenance treatment option after HSCT
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The results of a study published in 2020 showed that maintenance therapy with the histone deacetylase (HDAC) inhibitor Panobinostat combined with decitabine regimen after HSCT can reduce the recurrence rate of AML patients and improve the prognosis of AML patients
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Another study has explored Gemtuzumab Ozogamicin (GO), a combination of azacitidine and antibody-drug conjugate, as a maintenance treatment option for high-risk AML patients after HSCT
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The results of the study showed that the maintenance treatment regimen was well tolerated.
Compared with the control group, the experimental group had a 1-year overall survival (OS) rate (68.
8% vs 47.
9%; P=0.
13) and 1-year disease-free survival (DFS).
The rates (57.
0% vs 36.
5%; P=0.
24) were higher
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Preemptive treatment strategy after HSCT The phase II RELAZA study evaluated the efficacy of azacitidine preemptive treatment in patients with AML/MDS after HSCT.
The results of the study showed that azacitidine single-agent preemptive treatment can significantly increase the rate of donor cell mosaicism (DC ), while delaying the time of hematological recurrence
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50% of patients had DC>80%, and 30% of patients had DC<80% and did not relapse
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However, the incidence of grade 3-4 adverse events (AE) in the study was relatively high, with 80% of patients experiencing neutropenia, and 65% of patients experiencing thrombocytopenia
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The RELAZA2 study further explored the efficacy of azacitidine as a single-agent preemptive treatment after HSCT.
The results of the study showed that the 6-month DFS rate of azacitidine single-agent preemptive treatment was 58% (95%CI: 44%-72%) ), the most common grade 3-4 AE is neutropenia (85%)
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Salvage treatment strategy after HSCT The efficacy of azacitidine monotherapy in salvage treatment after HSCT is relatively inferior
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A phase II study included 39 patients with AML/MDS who relapsed early after HSCT and received azacitidine monotherapy as salvage therapy
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The results of the study showed that only 3 patients achieved complete remission (CR) after 6 months of azacitidine treatment, the overall remission rate (ORR) was only 31%, and the 2-year OS rate was 25%
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 In view of the poor effect of the single-drug rescue treatment program, some studies have explored the efficacy of the multi-drug combined rescue program
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The British Viola study explored the efficacy of azacitidine combined with the Bcl-2 inhibitor Venecla as a salvage treatment plan after HSCT
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The results of the study showed that 47% (7/15) of patients achieved major clinical remission (MCR), the median OS of patients who achieved disease remission was 27 months, and the median OS of patients who did not achieve disease remission was 10 months
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 Epigenetic drugs for the prevention and control of complications after HSCT can effectively prevent the occurrence of GVHD in AML/MDS patients after ASCT, and improve the prognosis of patients
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A study explored the use of the HDAC inhibitor vorinostat in combination with tacrolimus or methotrexate to prevent GVHD after HSCT
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The results of the study show that the program is safe.
The cumulative incidence of chronic GVHD after HSCT is 29%, and the cumulative incidence of acute GVHD is 22%
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Vorinostat has a significant preventive effect on GVHD in AML/MGS patients undergoing ASCT
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The Pediatrics team of Sun Yat-sen Memorial Hospital of Sun Yat-sen University explored the prevention and control of complications with the HDAC inhibitor Chidamide as a maintenance treatment
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The results of the study show that maintenance treatment with Chidamide can effectively reduce the incidence of acute GVHD in children
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 Professor Zhang Xi’s team also carried out a study, enrolling 204 high-risk AML patients from 12 centers in China, and explored the effect of granulocyte colony stimulating factor (G-SCF) pre-stimulated low-dose decitabine to prevent recurrence of AML patients after HSCT.
Effect
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The results of the study showed that G-SCF pre-excitation low-dose decitabine can significantly reduce the recurrence rate of AML patients after HSCT (15.
0% vs 38.
3%; HR: 0.
32; P<0.
01), and significantly increase the 2-year LFS rate (81.
9) % vs 60.
7%; HR: 0.
38; P<0.
01) and 2-year OS rate (85.
8% vs 69.
7%; HR: 0.
45; P=0.
01).
There was no significant difference in the 2-year incidence of chronic GVHD between the experimental group and the control group ( 23.
0% vs 21.
7%; HR: 1.
07; P=0.
82), the levels of NK cells, CD8+ T cells and Treg cells in the experimental group were higher than those in the control group
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The program is safe, the most common side effect is neutropenia, and no patient died due to side effects
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Subgroup analysis showed that the different subgroups of the experimental group were better than the control group in preventing recurrence
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Summary Professor Zhang Xi finally concluded: Epigenetics drugs have the effect of improving survival after HSCT, reducing disease recurrence after ASCT, and reducing GVHD.
It is an effective treatment for early recurrence after HSCT
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The combination of epigenetic drugs and drugs with different mechanisms of action is a new trend in maintenance therapy after HSCT
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Professor Zhang Xi Chief Physician, Professor, Doctoral (Post) Supervisor, Changjiang Scholar Distinguished Professor, Director of the Hematology Medical Center of Xinqiao Hospital, Army Military Medical University Director of the Hematology Center of the Chinese People's Liberation Army Standing Committee Member of the Hematology Branch of the Chinese Medical Association, Hematopoietic Stem Cell Application Group Deputy Team Leader Standing Committee Member of the Hematology Branch of the Chinese Medical Doctor Association Chairman of the 5th and 6th Chongqing Medical Association Hematology Special Committee Standing Committee Member of the Hematology Special Committee of the Chinese Anti-Cancer Association Standing Committee Member of the Experimental Hematology Special Committee of the Chinese Society of Pathophysiology The committee members presided over 39 national, provincial and ministerial-level projects; 72 SCI papers, with a maximum IF of 44.
5; 4 chief editors/associate editors; the first completer won 1 second prize of National Science and Technology Progress Award and 1 first prize of Chinese Medical Science and Technology Award.
2 first prizes for scientific and technological progress in Chongqing, 4 second prizes for scientific and technological achievements at the provincial and ministerial level; 16 national invention patents; 16 young Chinese oncology scientist awards; top-notch talents in the army; leading experts from Chongqing Chief Expert Studio; Chongqing Municipality Chief medical expert, Chongqing academic and technical leader, Chongqing science and technology innovation leader, Tianfu scholar special expert, first batch of army science and technology talents; JHO, Leukemia, Science Bulletin and other editors and reviewers stamp "read the original text", let's work together progress