Boyihui · International Conference Zone
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Foreword
As one of the largest and most comprehensive international academic events in the field of hematology in the world, the American Hematology Annual Meeting (ASH) will gather research experts in the field of hematology from around the world to jointly develop the latest basic frontiers, new methods and programs, and disease management strategies for blood diseases.
In recent years, China's research in the field of blood has made rapid progress, and more and more "Chinese voices" have resounded internationally. At this ASH Annual Meeting, a total of 62 studies by Chinese experts were selected for oral presentations. Professor Li Zhizhi of the Wu Tong Director Team of Beijing Gaobo Medical (Hematology) Beijing Research Center and Beijing Gaobo Boren HospitalA report titled "CD7 CAR-T Bridging Allogeneic Hematopoietic Stem Cell Transplantation Significantly Improves Long-Term Disease-Free Survival in Refractory ** T-cell Acute Lymphoblastic Leukemia Lymphoma" was performed (Abstract 239). The study is compiled for the benefit of readers.
What to study
Introduction:
The prognosis for refractory T-cell acute lymphoblastic leukemia lymphoma (R r T-ALL LBL) is poor, and the long-term disease-free survival (DFS) rate for salvage allogeneic hematopoietic stem cell transplantation (ALLO-HSCT) is only 20% to 30%. Our previous clinical trial showed a complete response (CR) rate of 90% in patients with R-ALL receiving CD7 chimeric antigen receptor T cells (CAR-T)** (Pan J.). et al.JCO 2021), and the 1-year DFS rate of 12 patients with rapid bridging ALLO-HSCT reached 57% (Li Zh et al. transplantation and cellular therapy 2022）。
Purpose:
In the present study, the investigators explored the long-term outcomes of bridging Allo-HSCT** after CD7 CAR-T in patients with R-T-ALL LBL in a larger study cohort and compared the prognosis of patients who received Allo-HSCT after chemotherapy. Prognostic-related risk factors were also analysed after receiving Allo-HSCT**.
Method:
The study included 90 patients with R R T-ALL LBL who underwent Allo-HSCT at our hospital between February 2018 and January 2023. The median age was 14 (2 65) years. Somatic and germline mutations are detected by genetic sequencing prior to transplantation. 32 cases (35.)6%) patients were sensitive to chemotherapy and reached CR before transplantation (Group A), 58 (64.)4%) resistant to chemotherapy and not in remission (NR) prior to transplantation. Of the 58 patients with NR, 41 received CD7 CAR-T** (Group B) prior to ALLO-HSCT, and the remaining 17 patients with NR received salvage transplantation (Group C). Donor types included haploidentical (60 cases, 66.)7%)), unrelated (16 patients, 178%) and siblings (14 cases, 15.)6%）。Total body irradiation (TBI)-based fludarabine (51,56.)7%) or busulfan fludarabine (39, 43.)3%). Antithymocyte globulin is used in haploidentical and unrelated transplantation. Cyclosporine, mycophenolate mofetil, and a short course of methotrexate are used to prevent graft-versus-host disease (**HD).
Results:
All patients were granted durable implants. There was no significant difference in the incidence of acute **HD (a**HD), chronic **HD (c**HD) and infection between the three groups (P=0.).612、p=0.091、p=0.649）。Median follow-up was 255（19.6 32) months, the 2-year overall survival (OS) rate in group B was similar to that in group A (54.).4% vs. 69.9%，p=0.33), much higher than group C (353%，p=0.0065）；The 2-year DFS rate in group B was similar to that in group A (51.).0% vs. 61.1%，p=0.24), much higher than in group C (17.)6%，p=0.0029）。There was no statistically significant difference in transplant-related mortality (TRM) between groups B, A, and C (17.)3% vs. 9.8% vs. 11.8%，p=0.65）。The 2-year cumulative rate of ** in group B (317%) with group A (290%), much lower than group C (70.).5%）。Compared to group C, group B (p=0.).0047) and group A (p=0.).0003) and the risk of death was significantly reduced. Pre-transplant NR (p=0.).0062）、a**hd（p=0.013) and viral infections (p=0.).047) was a risk factor for **-related mortality, but TBI-based conditioning regimens (P=001) is a protective factor of OS.
The most common somatic gene mutation is notch1 (55.)7%)、jak3(18.0%)、tp53(16.4%)、jak1(14.8%) and NRAS (14.)8%)。The most common germline gene mutation is EP300 (10.)3%）、atm（8.6%）、f7（8.6%）、kit（8.6%) and NCF2 (8%). Somatic TP53 mutations (P=0.).0018) or MED12 mutations (P=0.).0068). Germline gene mutations have no significant effect on prognosis after transfer.
Multivariate analysis showed that CD7 CAR-T (P=0.).037), TBI-based pretreatment scheme (p=0.).002) and c**hd (p=0.).004) is a protective factor of OS, while a**hd (p=0.).034) and TP53 mutations (p=0.).002) is a risk factor for OS. At the same time, CD7 CAR-T (P=0.005) and TBI-based pretreatment protocols (p=0.).024) protective effect on DFS, while TP53 mutation (P=0.).02) It also has a dangerous effect on DFS.
Conclusion:
This study showed that CD7 CAR-T bridging ALLO-HSCT significantly improved long-term DFS in chemotherapy-resistant T-ALL LBL patients, and that the safety and efficacy were comparable to those of chemotherapy-sensitive patients undergoing ALLO-HSCT. This study also revealed the somatic and germline gene mutations in R-T-all LBL, and identified some protective and risk factors that affect the prognosis of transplantation in this setting.
Expert presentation
Li Zhizhi
Chief Physician of the Third Ward of the Second Department of Hematology (Transplantation Technology) of Beijing Gaobo Medical (Hematology) Beijing Research Center, Beijing Gaobo Boren Hospital.
Doctor of Medicine, Capital Medical University;
Vice Chairman of the Digital Diagnosis and Treatment Committee of Hematology;
Member of the Pharmaceutical Biotechnology Clinical Application Professional Committee of the China Pharmaceutical Biotechnology Association;
Member of the Hematology and Oncology Committee of the Chinese Anti-Cancer Association;
Member of the National Society of Oncology Nutrition, Pediatric Oncology Nutrition Society;
Member of the Infection and Inflammation Radiology Committee of the Chinese Association of Research Hospitals
Member of the Hematopoietic Stem Cell Transplantation Professional Committee of the Beijing Cancer Prevention and Control Society.
He has been deeply engaged in clinical work and laboratory research in hematology for a long time, and has rich experience in the prevention and treatment of hematopoietic stem cell transplantation (HSCT)** leukemia, MDS, lymphoma, aplastic anemia, hemophagocytic syndrome and other diseases and transplant complications.
He has published several SCI articles in BMT, Frontiers in Immunology, Transplantation and Cellular Therapy, Leukemia & Lymphoma, Medicine, etc. He has spoken at several international hematology congresses such as the American Blood Annual Meeting, the European Blood Annual Conference EHA, the European Bone Marrow Transplant Annual Conference EBMT, and the Asia-Pacific Bone Marrow Transplant Annual Meeting APBMT.
International Conference Zone
The international academic event is not only a stage for experts and scholars in the field to show their academic style, but also an important platform for young clinicians to broaden their horizons and broaden their thinking.
Related Reading:
2.2023 ash |Prof. Tong Wu: CD7 CAR-T bridging transplantation**T-ALL New Strategy Targets the New Era Original Link|
Contents** Ioncology
Audit |Fang Yueli, Jia Dongxue.