October 6-9, 2022, the 27th Asia-Pacific Blood and Bone Marrow Transplantation Annual Meeting (APBMT 2022) will be held online. The APBMT conference is an important platform for technical cooperation and academic exchanges in hematopoietic stem cell transplantation in the Asia-Pacific region, aiming to comprehensively introduce the latest research progress in the fields related to bone marrow transplantation. At this APBMT conference, Gaobo Medical (Hematopathy) Beijing Research Center Beijing Gaobo Boren Hospital Wu Tong team Director Song Yanzhi Oral report "IMPROVED SURVIVAL WITH ALLO-HSCT FOR RELAPSED/REFRACTORY B-ALL IN NON-REMISSION OR MRD+ AFTER CART" (allo-HSCT can improve the survival prognosis of R/R B-ALL patients who have not been remission or have MRD-positive MRD) after CAR-T treatment, [Abstract No. 197]. The prognosis of patients with relapsed/refractory (r/r) acute B lymphocytic leukemia (B-ALL) who cannot completely relieve (CR) after treatment with CAR-T. The team of Wu Tong, director of Beijing Gaobo Boren Hospital, director of Song Yanzhi, team of Song of Beijing evaluated the efficacy and safety of allo-HSCT in patients with r/r B-ALL who cannot obtain CR [non-remission (NR) or micro-residual disease (MRD) positive (+)] after CAR-T treatment.
Gaobo Boren hematopoietic stem cell transplantation team included 38 r/r B-ALL patients who received NR (12 cases) or MRD+ (26 cases) after CAR-T and received allo-HSCT. Among them, 22 patients (57.9%) received at least two CAR-T treatments before allo-HSCT. Myeloablative pretreatment protocol was used in all patients. Some patients received targeted drug maintenance therapy for up to 2 years after transplantation. The results of the
study showed that all 37 patients achieved stable implantation. There was no difference in the two-year OS (overall survival, Figure 1) and LFS (-free leukemia- survival, Figure 2) in patients in NR and MRD+ groups.
Figure 1 OS
Figure 2 LFS
▶ For patients with NR and MRD+, the median follow-up time was 150 (39-1127) days. Among them, 4 patients had no leukemia, had MRD negative, and 8 died of recurrence. In two years, OS and LFS were 32.7% and 25.4% respectively. No patient died of transplant-related incidents. Three patients developed grade III-IV acute graft-versus-host disease (aGVHD), and two patients developed extensive chronic GVHD (cGVHD). One patient died of grade IV aGVHD and relapse, while other patients were treated with immunosuppressant . CMV and EBV reactivation was detected in 7 and 1 patient. One patient suffered from severe lung fungal infections in and bacteremia in respectively. Two patients developed severe hemorrhagic cystitis.
▶ For MRD+ patients, the median follow-up time was 258 (39-1389) days, with OS and LFS of 41.4% and 30.5% in two years, respectively. 15 patients relapsed. Six patients developed grade III-IV aGVHD, and three patients developed cGVHD. Two patients died of grade IV aGVHD, and all other problems were resolved. CMV and EBV reactivation occurred in 11 and 4 patients. Four patients developed bacteremia. Mild and severe hemorrhagic cystitis occurred in 12 cases and 1 case, respectively.
▶ One-way regression analysis showed that age, gender, CAR-T times, first or second HSCT did not affect the results.
The preliminary study results show that rescue allo-HSCT significantly improves the survival rate of r/r B-ALL patients who fail both chemotherapy and CAR-T treatment, and have a lower transplant-related mortality rate (3/38). For patients with r/r B-ALL who are treated with such severe treatment (still in NR or MRD+ after CAR-T treatment), allo-HSCT is both safe and effective.
Director Song Yanzhi talked about the poor prognosis of B-ALL with relapsed/refractory B-ALL, and the CR and LFS rates of salvage chemotherapy and salvage allo-HSCT were both low. At present, many studies have confirmed that antibody treatment (such as CD3/CD19 dual antibody, CD22 antibody), CAR-T treatment, and targeted drugs combined with chemotherapy have better efficacy in r/r B-ALL. Among them, CAR-T is currently recognized as the best treatment method for r/r B-ALL. CAR-T treatment can give about 95% of r/r B-ALL patients a chance to transplant. However, about 5% of patients still fail to achieve CR using CAR-T treatment.
For these patients, there has never been a good clinical treatment method. If left untreated or routine chemotherapy is used, the patient's survival may be only a few months and the prognosis is very poor. Therefore, for these patients, our team used rescue allogeneic hematopoietic stem cell transplantation to achieve certain therapeutic effects. Many patients achieved long-term survival and saved the lives of some patients.
After our research, we found that the patient's organ function before was good, and there were no serious infections or serious comorbidities, which was the key to achieving good efficacy and safety in the transplant. We included 38 patients, and there were only 3 deaths caused by transplant-related comorbidities, and the total transplant-related mortality rate did not increase. Even for patients with high treatment, salvage transplantation remains an effective and safe treatment.
In addition, after transplantation, we selected corresponding targeted drugs for maintenance treatment according to the patient's tumor mutation gene. Some patients can also use conventional maintenance treatment methods, such as decitabine, lenalidomide and maintenance treatment. Maintenance of targeted drug has obvious therapeutic effects on consolidating the efficacy of transplantation, prolonging the survival of patients, and improving the cure rate.
Overall, our preliminary research results show that rescue transplantation is still an effective treatment for patients with r/r B-ALL who have not been effective after repeated treatment, which may enable some patients to regain complete remission and achieve long-term survival and cure.
Summary
With the continuous development of medical technology and drug development, treatment methods including targeted drugs, monoclonal antibody drugs, and CAR-T technology have made a great breakthrough in the treatment of acute leukemia . At the same time, hematopoietic stem cell transplantation technology has also been continuously improving and has made great progress. for high-risk patients, rescue transplantation can still achieve good results and is very safe. At present, the efficacy of transplantation is getting better and better, and patients do not need to give up the opportunity to transplant because they are worried that the incidence of serious comorbidities after transplantation is too high.
■ Expert introduction
Director Wu Tong
Hot cell transplantation discipline in Gaobo Medical (Hematology Diseases) Research Center.
Gaobo Medical (Hematopoietic Diseases) Beijing Research Center Director of Hematopoietic Stem Cell Transplantation Department and Director of Medical Sciences.
Member of the Academic Committee of the Asia-Pacific Bone Marrow Transplantation Society, member of the Standing Committee of the Hematopoietic Stem Cell Transplantation and Cell Therapy Group, and Deputy Chairman of the Targeted Therapy Professional Committee of the Female Physicians Association.
graduated from the Department of Medical Sciences of Beijing Medical University (now Peking University School of Medicine ). From 1986 to 2006, he served as a resident, attending physician, and deputy chief physician at the Institute of Hematology at Peking University People's Hospital, engaged in the diagnosis and treatment of blood diseases. Since 1987, his main work area has been hematopoietic stem cell transplantation. From 2006 to 2012, he served as director of the Department of Hematopoietic Stem Cell Transplantation at Beijing Daopei Hospital. From 2012 to 2015, he served as deputy director of Lu Daopei Hematologic Cancer Center and director of the Hematopoietic Stem Cell Transplantation Department of Hebei Yanda Hospital. From 2015 to April 2017, he served as deputy director of Hematopoietic Stem Cell Transplantation Department and director of the Department of Hematopoietic Stem Cell Transplantation.
Since May 2017, he served as the director of the Hematopoietic Stem Cell Transplantation Department and the director of the Medical Department of Beijing Boren Hospital. In 1994, he studied viral diagnosis at the Institute of Virology, Chinese Academy of Medical Sciences. From 1996 to 2000, he was a postdoctoral fellow at the Institute of Cardiology, Lung and Blood of NIH (National Institutes of Health), and his main research direction was hematopoietic stem cell gene therapy.
has been engaged in hematopoietic stem cell transplantation for more than 30 years and is an internationally renowned hematopoietic stem cell transplantation expert.There are thousands of transplant experiences (1-72 years old), and have unique successful experiences in the selection of transplant methods (donor, pretreatment scheme), treatment of graft-versus-host disease (GVHD) and infection, transplantation of refractory/recurrent leukemia and prevention and treatment of relapse after transplantation, immunotherapy (for leukemia, virus, fungi), CAR-T bridged transplantation, transplantation of geriatric leukemia, secondary allogeneic transplantation, etc. A relatively mature transplant system has been established, and the hematologic tumors (leukemia, MDS, lymphoma, , etc.) and benign hematologic diseases (alia, PNH, hematophagocytosis, etc.) have reached a level with few comorbidities and a high disease-free survival rate.
is a member of the Hematology Branch of the Chinese Medical Association, a member of the American Hematology Society, a member of the International Hematology Society, a member of the Asia-Pacific Bone Marrow Transplantation Society (APBMT) and a member of the Academic Committee, a member of the Standing Committee of the Hematology Tumor Professional Committee of the China Anti-Cancer Association and a Deputy Head of the Hematopoietic Stem Cell Transplantation and Cell Therapy Group, a Deputy Chairman of the Targeted Therapy Professional Committee of the China Female Physicians Association, a member of the Hematology Professional Committee of the China Female Physicians Association, and a member of the Integrated Hematology Professional Committee of the China Physicians Association. He serves as the editor of the Chinese Journal of Hematology, Hematology/Oncology and Stem Cell Therapy and Blood Chinese Version.
published more than 90 papers and spoke dozens of times at international conferences. He has won the Outstanding Teacher Award, the Second Prize in English Teaching, the Second Prize in Chinese Medical Science and Technology Progress, the First Prize in Beijing Science and Technology Progress, the Second Prize in Science and Technology Progress of the General Logistics Department of the People's Liberation Army, the Top Ten Paper Award and the Outstanding Speech Award.
Director Song Yanzhi
Gaobo Medical (Hematopathy) Beijing Research Center Beijing Gaobo Boren Hospital Department 2 (transplantation technology) Ward 1, Deputy Chief Physician.
has more than 10 years of clinical work experience and has been engaged in allogeneic hematopoietic stem cell transplantation for a long time. Expert in: Allogeneic hematopoietic stem cell transplantation and the treatment of various common transplant complications.
Member of the Transplantation and Plasma Swap and Plasma Swap Group of Stem Cell Engineering Technology Branch of the Chinese Society of Biomedical Engineering.
McMaster University Health Information Research Center Evidence-Based Resources Rater.
As the corresponding author of published several SCI papers , with the highest impact factor 12.
"Cochrane Database of Systematic Review", "Plos One", "Journal of Integratieve Medicine" and other SCI included magazine reviewers.
