2022CSH Transmission Transplantation Progress, Interpretation of Academic Frontiers, the 17th National Hematology Academic Conference of the Chinese Medical Association - Hematopoietic Stem Cell Transplantation Group Forum was successfully concluded

Listen to the sound of blood and feel the rhythm of life
.
The 17th National Hematology Academic Conference of the Chinese Medical Association, sponsored by the Chinese Medical Association and the Hematology Branch of the Chinese Medical Association, hosted by the Shanghai Medical Association, and 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, has been solemnly held
on September 23-25, 2022.

"Respect, inheritance, collaboration, innovation", adhering to this purpose, many well-known experts at home and abroad talked about the latest progress
in the field of blood diseases.
At the hematopoietic stem cell transplantation group forum on September 24, a number of academic experts shared topics and paper interpretations to discuss the frontiers of hematopoietic stem cell transplantation
.
Medical Pulse has now compiled the wonderful content below for the benefit of readers
.

Feature sharing chapter

01











Prevention and treatment of recurrence after transplantation

Under the co-chairmanship of Professor Yang Jianmin of the First Affiliated Hospital of Naval Military Medical University (Shanghai Changhai Hospital) and Professor Zhang Yicheng of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Professor Xia Linghui of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology shared the progress of
relapse prevention and control after allogeneic hematopoietic stem cell transplantation (allo-SCT) in patients with high-risk acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS).
。 Allo-SCT is an important treatment for AML patients, allo-SCT after the recurrence of disease is an important cause of patient death, its recurrence may have multiple source mechanisms, such as human leukocyte antigen (HLA) mutation, cell programmed death ligand 1 (PD-L1), CD155 and other molecules overexpression leading to immune escape
.
Relapse prevention and control involves the whole process of transplantation, mainly including pre-transplant bridging plan, pretreatment plan selection, post-transplant prevention, preemptive treatment and post-recurrence intervention, and a variety of measures to individualize the policy
.
Among them, prevention is better than preemptive treatment, preemptive treatment is better than hematological recurrence treatment, and care should be taken to avoid overtreatment
.

Post-transplant infection prevention

Under the co-chairmanship of Professor Chen Xiequn of the Affiliated Hospital of Northwest University and Professor Liu Lin of the First Affiliated Hospital of Chongqing Medical University, Professor Gao Sujun of the First Hospital of Jilin University shared the prevention and treatment
of non-cytomegalovirus (CMV)/EBV infection after allo-SCT.
The incidence of infection-related complications after allo-SCT is high, and the pathogen is predominantly
viral.
In addition to common viral infections such as CMV/EBV, other rare viral infections after transplantation are also worthy of attention, and some viral infections may be an important cause of
non-recurrent death.
With the application of new pathogen metagenome sequencing technology, it may deepen clinicians' understanding of post-transplant pathogen infection and provide a reference for
the diagnosis and treatment of infection-related complications.

Paper Interpretation 02












Clinical outcomes and efficacy of TPE in the treatment of TA-TMA in a large real-world study

Under the auspices of Professor Yang Ting of Union Hospital affiliated to Fujian Medical University, Professor Yang Liping of Peking University People's Hospital analyzed a real-world retrospective study
of transplant-associated thrombotic microangiopathy (TA-TMA) with plasmapheresis (TPE) treatment conducted by his team.
The aim of this study was to identify the beneficiaries of TPE therapy and to optimize TA-TMA treatment strategies
.
Studies have found that the number and duration of TPE use, the cumulative amount of TPE replacement, intestinal bleeding and hypertension may affect the efficacy of TPE in the treatment of TA-TMA, and the use of TPE in patients with TA-TMA with intestinal bleeding is not effective and the risk of death is increased
.
The results of the study showed that TPE application may reduce the risk of death of TA-TMA, and that the use of TPE in sufficient amounts and sufficient courses of treatment can benefit patients with TA-TMA
.

Allo-SCT anterior bridging CAR-T cell therapy reverses the adverse prognosis of R/R B-ALL

Under the auspices of Professor Ye Baodong of Zhejiang Provincial Hospital of Traditional Chinese Medicine, Dr.
Wu Haotian, a team of Professor Zhao Xiangyu of Peking University People's Hospital, shared new findings
on the treatment of refractory/recurrent acute B lymphoblastic leukemia (R/R B-ALL).
This study explored the effect of
allo-SCT pre-bridging chimeric antigen receptor T cell (CAR-T) therapy on R/R B-ALL adverse prognosis from various indicators before and after allo-SCT 。 The study found that lower levels of pre-transplant donor-specific antibodies (DSAs) in the CAR-T group would help reduce the risk of post-transplant immune rejection; The higher proportion of immunoreconstructed T cells in the CAR-T group within 6 months after transplantation may be associated with a lower incidence of grade II-IV acute graft-versus-host disease (aGVHD) in this group; The study confirmed that allo-SCT anterior bridging CAR-T therapy improved post-transplant prognosis in patients with R/R B-ALL, but the sample size was limited and further exploration was needed to provide strong evidence
.

Comparative study of the efficacy of SAA in children with UCBT and IST

Under the auspices of Professor Jiang Jieling of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Professor Zhao Xuxu of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) introduced the comparative study
of the efficacy of non-blood cord blood transplantation (UCBT) and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA).
。 The results showed that first-line UCBT therapy may be a better treatment than IST in children with SAA without sibling donor (MSD), with high implantation success rate, good long-term survival (3-year survival rate of 89.
5% vs 42.
1% progression without failure), and excellent quality of life (no moderate to severe chronic graft-versus-host disease [cGVHD], fast transition from transfusion dependence).

BuCy versus TBI-Cy in the treatment of B-ALL in adults: an open-label, multicenter phase III trial

Under the auspices of Professor Liu Chuanfang of Qilu Hospital of Shandong University, Professor Zhang Haiyan of Southern Hospital of Southern Medical University shared the application
of busulfan combined with cyclophosphamide (BuCy) versus systemic radiotherapy (TBI) combined with cyclophosphamide (TBI-Cy) in adult B-ALL.
TBI-based pretreatment protocols are widely used in allo-SCT and have strong antitumor effects, but the side effects of high-dose radiotherapy seriously affect patient survival and quality of
life.
The study compared post-transplant outcomes in patients who received two pretreatment regimens and found that the efficacy and safety of the BuCy pretreatment regimen was not inferior to that of the TBI-Cy protocol
in adults who received sibling fully compatible allo-SCT after the first complete response.

Single-cell sequencing elutes the role of T cells in aGVHD

Under the auspices of Professor Li Xin of the Third Xiangya Hospital of Central South University, Professor Pan Zengkai of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine analyzed the role of
single-cell sequencing in the resolution of T cells in aGVHD.
aGVHD is an important factor in determining the success of allo-SCT, and T cells play an important role
in the onset of aGVHD.
The expression and function of each subset of T cells at the onset of aGVHD are different, and CD8+ TEFF is the main cytotoxic effector cell; CD8+ TEM has the characteristics of proliferation, chemotaxis, cytotoxicity and depletion, and rapid proliferation provides reserves for effector cells, of which CD8+ TEM 1 (depletion, cytotoxicity) increases in the proportion at the onset of aGVHD, accompanied by upregulation
of the expression of T cell effector genes and functional gene sets 。 The proportion of CD8+ TEM and CD8+ TEFF cells at the onset of hormone-resistant aGVHD (SR-aGVHD) increased, and the expression of CD8+ TEM hormone receptor NR3C1 decreased, accompanied by JAK-STAT signaling pathway activation; The proportion of CD8+ TEM3 (cytotoxic, proliferative) cells is increased, with activation
of multiple signaling pathways.

Multicenter prospective clinical study of TCRαβ+/CD45RA+ cell affinity hemiferous hematopoietic stem cell transplantation in children with AL removal

Under the auspices of Professor Jin Hua of Nanfang Hospital of Southern Medical University, Professor Luo Chengjuan of Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine shared the application
of hemiconjunctive hematopoietic stem cell transplantation in the treatment of acute leukemia (AL) in children by removing TCRαβ+/CD45RA+ cell affinity 。 The study found that the removal of TCRαβ+/CD45RA+ cell affinity hemiconjunctive hematopoietic stem cell transplantation is safe and feasible; Complications such as infection, mucositis, implantation syndrome, and viral recurrence were significantly reduced compared with traditional semi-concomitant transplantation, and no transplant-related deaths occurred; The average follow-up was nearly 1 year, and the recurrence rate was comparable to that of traditional transplantation methods, and long-term follow-up was still required to see the long-term efficacy; Further improvements in the pretreatment protocol are needed to overcome the high implantation failure rate
.

The selective JAK1 inhibitor SHR0302 combined with prednisone first-line treatment of allo-SCT post-cGVHD

Under the auspices of Professor Li Limin of Southern University of Science and Technology Hospital, Professor Qiu Huiying of Shanghai First People's Hospital shared his team's Phase I study
on the selective JAK1 inhibitor SHR0302 combined with prednisone first-line treatment of allo-SCT for cGVHD.
Early findings showed that the overall response rate for 4 weeks was 94%, the complete response rate was 22%, the partial response rate was 72%, and no unexpected adverse events were observed, and SHR0302 plus prednisone first-line treatment with allo-SCT was safe and effective, and further sample size studies
need to be expanded in the future.

Safety and efficacy of preemptive treatment of aGvHD under MAP scores

Under the presidency of many Rong professors of the First Affiliated Hospital of Sun Yat-sen University, Professor Ji Jie of West China Hospital of Sichuan University introduced the first-mover treatment strategy
of aGVHD based on the aGVHD International Working Group Algorithm (MAP) of Mount Sinai.
MAP scores based on biomarkers ST2 and Reg3a in the early stages of transplantation predict severe aGVHD-related mortality and provide a basis
for preemptive treatment.
Preemptive treatment with methadron on post-transplant cyclophosphamide (PTCy)-based prophylaxis in patients in the high-risk MAP score group reduced the incidence of severe aGVHD and early non-recurrence mortality after transplantation, and did not increase the risk
of CMV reactivation and hemorrhagic cystitis.
However, the long-term efficacy and safety of preemptive treatment of aGVHD remains to be seen
.

The correlation between donor TCR diversity and immune remodeling of recipients after allo-SCT surgery

Under the auspices of many Rong professors from the First Affiliated Hospital of Sun Yat-sen University, Professor Huang Xiaobing of Sichuan Provincial People's Hospital explained the effect of
donor's T cell immune status on recipient immune remodeling after transplantation 。 The donor's low T cell receptor (TCR) richness was positively correlated with the incidence of aGVHD and cGVHD after transplantation, and the recurrence rate and CMV infection rate of the recipient with low TCR uniformity of the donor may be higher than that of the recipient with high TCR uniformity; High TCR richness and high TCR uniformity of donors may mean a low recurrence rate for recipients, and donor immune status has an impact on recipient immune reconstitution after transplantation, and future assessment of donor immune status can be used to optimize transplant donor selection
.

Risk factors and predictive models for early recurrence after allo-SCT in patients with AML

Under the auspices of Professor Chen Xinchuan of West China Hospital of Sichuan University, Professor Yuan Xiaolin of the First Affiliated Hospital of Zhejiang University School of Medicine introduced the risk factors and prediction models
for early recurrence after allo-SCT in AML patients.
Primary drug resistance, positive pre-transplant minimal residual disease, DNMT3A mutation, leukocyte > 20×¹⁰⁹/L are independent risk factors for recurrence within 1 year after transplantation, and predictive models based on these risk factors can help identify high-risk relapse patients, and early identification for early intervention is expected to reduce recurrence and improve prognosis
.

Prognostic prediction of new risk scores (AML-DRG and AML-HCT-CR) for AML allo-SCT patients

Under the auspices of Professor Lu Yue of Hebei Yanda Ludaopei Hospital, Professor Cao Weijie of the First Affiliated Hospital of Zhengzhou University introduced the clinical research
of his center on the prognosis model of AML allo-SCT.
Pre-transplant risk and survival assessment is key
to optimizing AML transplant effectiveness.
The study conducted a retrospective analysis of 123 AML patients receiving allo-SCT, and confirmed that the two AML-specific scores, AML-DRG and AML-HCT-CR, had predictive effects on the total survival and progression-free survival of AML patients after transplantation, and further analysis of the causes of death in each risk group found that it mainly affected the overall survival of patients by influencing post-transplantation recurrence, and further expansion of sample size or further verification by joint multi-center in
the future.

Effect of HLA-B pilot sequence on haploid hematopoietic stem cell transplant outcomes

Under the auspices of Professor Zhang Jianhua of the Second Hospital of Shanxi Medical University, Professor Wang Mingyang of the Blood Disease Hospital of the Chinese Academy of Medical Sciences explained in detail the effect of
the HLA-B pilot sequence on the transplantation outcome.
The HLA-B pilot sequence encodes 2 amino acids: methionine (M) or threonine (T), and the HLA-B pilot sequence for each individual may be MM, TT, or MT
.
The study divided patients into HLA-B mismatch and HLA-B match groups, and found that the HLA-B mismatch group had shorter overall survival and higher non-recurring mortality, while the HLA-B match group shared M recurrence rate was higher, and shared T had longer
overall survival and disease-free survival.

Dynamic prediction of severe aGVHD after transplantation

Under the auspices of Professor Zhang Jianhua of the Second Hospital of Shanxi Medical University, Professor Cao Yigeng of the Hematology Hospital (Institute of Hematology) of the Institute of Hematology of the Chinese Academy of Medical Sciences shared the dynamic prediction model of severe aGVHD after transplantation - the daGOAT adaptive algorithm, which updates the patient's laboratory test data every day to predict the risk of aGVHD and give preventive administration, and its predictive power is significantly better than the MAGIC score, Ann Arbor score, The static model and XGBoost dynamic model based on peritransplantation characteristics are more suitable for clinical application and are helpful for clinical decision-making
.

HucMSCs that overexpress miR-126-3p miCMSCs alleviate aGVHD endothelial damage by modulating VCAM-1 and PIK3R2

Under the auspices of Professor Yuan Hailong of the First Affiliated Hospital of Xinjiang Medical University, Professor Li Ziying of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology shared an exploratory study
on whether human umbilical cord mesenchymal stem cells (hucMSCs) combined with miR-126-3p may enhance the repair effect of aGVHD endothelial injury 。 In vitro experiments showed that miR-126-3p overexpression could enhance the protective effect of hucMSCs on endothelial cells, and miR-126-3p combined with hucMSCs could promote angiogenesis, improve vascular endothelial functional defects, reduce the severity of aGVHD, and improve the survival rate of transplanted mice.
Vascular cell adhesion molecule-1 (VCAM-1) and phosphoinositol 3-kinase regulatory subunit 2 (PIK3R2) are two direct target genes for miR-126-3p-hucMSCs-mediated aGVHD injury endothelial repair and have organ heterogeneity
.

AL with unresolved treatment of haploid blood transplantation with haploid blood transplantation: a multicenter study

Under the auspices of Professor Li Yuan of Peking University First Hospital, Professor Zhu Jinjin of the First Affiliated Hospital of Soochow University introduced the optional transplantation method that has not alleviated AL
.
The poor prognosis of patients with unresolved AL, and the overall efficacy of haploid-umbilical cord blood transplantation and haploid transplantation are similar, which can improve the prognosis of these patients, but there is a lagging effect on the prognostic effect of haploid-umbilical cord blood transplantation on patients who have not alleviated AL, which is expected to improve the long-term prognosis
of surviving patients.

Efficacy and safety of CD19-specific CAR-T cell immunotherapy in the treatment of central nervous system lymphoma

Under the auspices of Professor Ma Liangliang of the First Affiliated Hospital of Dalian Medical University, Professor Zhang Huanxin of the Affiliated Hospital of Xuzhou Medical University interpreted the retrospective study
of relapsed/refractory secondary central nervous system lymphoma (R/R SCNSL) for treatment with CD19-based CAR-T.
Compared with traditional treatment regimens, CAR-T cell therapy has a better and safe treatment of R/R SCNSL, and the central efficacy of SCNSL patients with systemic tumor infiltration is more durable
than that of systemic tumors.

A phase II, multicenter, randomized controlled study of MSC transfusion of haploid hematopoietic stem cells for the prevention of GVHD 45 days after transplantation

Under the auspices of Professor Ma Liangliang of the First Affiliated Hospital of Dalian Medical University, Professor Chen Ting of Xinqiao Hospital of Army Military Medical University shared the significance of infusion of
hucMSCs 45 days after haploid hematopoietic stem cell transplantation.
Repeated infusions of hucMSCs 45 days after haploid transplantation improved the absence of GVHD-no recurrence (GRFS) and reduced the incidence
of grade III-IV aGVHD, cGVHD, and grade III-IV hemorrhagic cystitis.

Summary
03

After the wonderful academic exchanges and sharing, the forum came to a successful conclusion
.
Hematopoietic stem cell transplantation is an important treatment method for hematological tumors, with the application of more new drugs, the optimization of prognosis prediction scores, the management of the whole process of transplantation and the improvement of transplantation technology, I believe that China's hematopoietic stem cell transplantation cause will become more and more mature, bringing long-term survival benefits to more patients!

Editor: Arya Review: Moon Typesetting: Moly Execution: Moly

Poke "Read the original article" and go to the micro-official website to get more meeting information