Editor’s Note: The 50th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) was held with great fanfare in Glasgow, UK, from April 14 to 17, 2024. The conference focused on the latest advancements in stem cell transplantation and cellular therapy, pushing forward better clinical outcomes for patients with blood diseases and hematological malignancies. At this year’s conference, a study by the team of Professor Ruijuan Sun from Hebei Yanda Lu Daopei Hospital in China was included for poster presentation. The study revealed that using CD7-CAR-T cell therapy as a bridge to stem cell transplantation showed similar efficacy and safety in treating pediatric acute T-cell lymphoblastic leukemia compared to those who received chemotherapy and then underwent transplantation. This publication has the privilege of inviting Professor Ruijuan Sun to share the research findings and their clinical implications with peers immediately.
Research Background:
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a method for curing children with high-risk lymphoblastic leukemia. After the first relapse of T-cell acute lymphoblastic leukemia (T-ALL), the probability of achieving long-term survival with chemotherapy alone is about 15%. This study aims to compare the long-term survival rate (OS), incidence of acute graft-versus-host disease (aGVHD), and rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections between CD7-CAR-T cell therapy as a new bridging treatment to transplantation and traditional chemotherapy followed by transplantation.
Research Methods:
A retrospective analysis was conducted on 90 pediatric T-ALL patients, aged 14 or younger, who underwent Allo-HSCT at Hebei Yanda Lu Daopei Hospital from October 2010 to June 2023. Before transplantation, 28 patients achieved hematological remission (CR) with CD7-CAR-T cell therapy, and 62 achieved CR with chemotherapy. The median age was 9 years (range 1-14), with a male to female ratio of 68:22. Of these, 59 patients achieved their first hematological remission (CR1) before transplantation (14 in the CAR-T group and 45 in the chemotherapy group). Additionally, 31 patients had at least one hematological relapse before achieving remission again (≥CR2) after treatment, including 14 in the CAR-T group and 17 in the chemotherapy group.
In terms of donor sources, there were 7 matched sibling donors, 10 unrelated non-blood-related donors, and 73 haploidentical donors. 76 patients received a conditioning regimen primarily consisting of TBI/CY/ATG, while 14 received a regimen based on BU/CY/ATG. Prevention of GVHD was uniformly managed using cyclosporine or tacrolimus combined with mycophenolate mofetil and short-course methotrexate.
Research Results:
After a median follow-up of 16 months (range 1-37 months), all 90 patients successfully engrafted and achieved complete donor chimerism. The results showed that the one-year post-transplant relapse rates were similar between the two groups, 3.8% in the CAR-T group versus 5.2% in the chemotherapy group (P=0.846); long-term survival rates were 81.5% for the CAR-T group and 86.7% for the chemotherapy group (P=0.572). There were no significant differences in the incidence of Grade II-IV aGVHD (17.9% vs. 16.1%, P=0.896) and Grade III-IV aGVHD (7.6% vs. 13.3%, P=0.421) between the groups.
Research Conclusion:
In this single-center data analysis, pre-transplant CD7-CAR-T cell therapy in children with T-ALL is safe and effective. Bridging to Allo-HSCT with CD7-CAR-T cell therapy does not increase the incidence of GVHD or CMV and EBV viremia.
Researcher’s Statement:
Cellular and targeted therapies can improve survival outcomes for children with T-ALL. Bridging to Allo-HSCT with CD7-CAR-T cell therapy improves overall survival (OS) in children with refractory/relapsed T-ALL. The incidence of aGVHD in the Allo-HSCT group treated with CAR-T cells shows no significant difference compared to the concurrent non-CAR-T treatment group. There are also no significant differences in the incidence of CMV/EBV viremia post-transplant. Therefore, we recommend that children with high-risk T-ALL undergo Allo-HSCT in a state of complete remission (CR) whenever possible.
Professor Ruijuan Sun at EBMT 2024 Event
Expert Profile
Ruijuan Sun
– Member of the Organ Cellular Disease Professional Committee of the Hematology Physicians Branch of the Chinese Medical Doctor Association.
– Member of the Umbilical Cord Blood Application Committee of the China Maternal and Child Health Association.
– Member of the Langfang City Cancer Association in Hebei Province.
Professor Sun has been engaged in clinical work related to hematopoietic stem cell transplantation for over 20 years and has successfully completed over a thousand cases of allogeneic hematopoietic stem cell transplants, with patient ages ranging from 7 months to 69 years. She has extensive experience in treating various types of benign and malignant blood tumors, acute and chronic GVHD, severe infections, and various post-transplant complications, especially in using immunotherapy to prevent post-transplant relapse. She has been involved in the completion of the first case of autologous umbilical cord blood treatment for severe aplastic anemia in children in China and the first transplant for XIAP-related hemophagocytic syndrome. She has also successfully completed multiple cases of stem cell transplantation for congenital ichthyosis and has shared her experiences at international bone marrow transplantation conferences such as APBMT, EBMT, and TCT.
