Editor’s note: Graft failure is a rare but fatal complication following haploidentical allogeneic hematopoietic stem cell transplantation. A second transplant is almost the only salvage measure for transplant failure. However, outcomes from second transplants have generally been poor, as reported in previous literature. The 50th European Society for Blood and Marrow Transplantation (EBMT) annual meeting was held in Glasgow, UK, from April 14th to 17th, 2024. The conference focused on the latest advancements in stem cell transplantation and cellular therapy, driving better clinical outcomes for patients with blood disorders. At this conference, a team led by Professor Yuqian Sun from Peking University People’s Hospital presented their findings in an oral report titled “Salvage Haploidentical Transplantation with Flu/Cy Regimen and Donor Switching After Primary Graft Failure: Follow-Up Results,” which garnered significant attention. Professor Sun was invited to share the main results of this study and the progress in salvage treatments for graft failure after haploidentical allogeneic hematopoietic stem cell transplantation.
Graft Failure: A Rare but Fatal Complication
Graft failure (GF) is an exceedingly rare but challenging issue post-transplant, with an incidence rate of only 5%-10%. It leads to adverse events such as infections, bleeding, and organ damage. Without rescue treatments, the mortality rate of GF approaches 100%, and effective treatment options are scarce. The primary method is undergoing a second hematopoietic stem cell transplant.
Challenges of Second Transplant
Second transplants face significant challenges; currently, there are no unified standards for preconditioning regimens, donor selection, or GVHD (graft-versus-host disease) management plans, and overall therapeutic effectiveness is limited. Previous studies reported 1-year overall survival (OS) rates from second transplants between 11-37%.
Factors Contributing to Graft Failure
Graft failure can be categorized into graft rejection and poor implantation. Various factors contribute to GF, such as donor-recipient matching, the intensity of preconditioning, type of graft, cell count infused, underlying diseases, and GVHD prevention plans.
Improved Outcomes with Salvage Transplantation
Professor Sun’s team used the Flu/Cy regimen and changed donors for salvage transplantation, significantly improving survival in GF patients. Their small-scale study published in 2021 included 13 patients, showing promising results with a median follow-up time of 515 days (92-869 days) for survivors. At the last follow-up, seven patients were still alive, while six had died, four from transplant-related mortality and two from disease relapse. One-year OS and disease-free survival (DFS) after the second transplant were 56.6% and 48.4%, respectively.
Expanded Study and Results
The recent oral report expanded on past work, including 30 patients (previously reported 13). The median time to the second transplant after the first was 96.5 days (33-215 days). Of these, 28 used different haploidentical donors, with only two reusing the same donor due to a lack of alternatives. One patient died 19 days post-second transplant. Of the 29 evaluable patients, all achieved successful neutrophil engraftment by a median of 11 days (8-24 days), and 22 achieved successful platelet engraftment by a median of 17.5 days (9-140 days). The 1-year OS was 60%, and DFS was 53.3%. The 1-year cumulative incidence of relapse (CIR) and transplant-related mortality (TRM) were 6.7% and 33.3%, respectively. Compared to a historical control group (n=34), the new regimen significantly improved neutrophil engraftment rates (100% vs. 58.5%, P<0.001) and platelet engraftment rates (75.8% vs. 32.3%, P<0.001), as well as 1-year OS (60.0% vs. 26.4%, P=0.011).
Future Directions
Looking forward, Professor Sun noted there is still much room for improvement. Multi-center studies are needed to further validate these results, and transplant and GVHD management plans can be further optimized. The goal is to refine and personalize GVHD prevention to further improve patient survival. By delving deeper into basic medical mechanisms and expanding clinical practice, the team hopes to explore whether changing donors and what types of donors can optimize patient survival. Professor Sun emphasized that the future efforts will continue to focus on improving patient survival relentlessly.
Dr. Yuqian Sun
Dr. Yuqian Sun is a Medical Doctor, Chief Physician, Associate Professor, and Doctoral Supervisor. He serves as the Director of Hematology at Peking University People’s Hospital Shunyi Campus and is affiliated with the National Clinical Research Center for Hematologic Diseases and the Hematology Institute of Peking University.
Professional Positions and Roles:
– Committee Member and Secretary of the Hematopoietic Stem Cell Application Group, 11th Committee of the Chinese Medical Association Hematology Branch
– Committee Member of the Thrombosis and Hemostasis Group, 10th Committee of the Chinese Medical Association Hematology Branch
– Secretary-General of the Fungal Diseases Committee, Chinese Medical Education Association
– Member of the Youth Committee, Beijing Medical Association Hematology Branch
– Member of the Transplant Infection Group, Geriatrics Hematology Branch, Chinese Society of Geriatrics
– Young Committee Member of the Infectious Diseases Committee, Chinese Medical Education Association
– Senior Visiting Scholar, European Society for Blood and Marrow Transplantation (EBMT)
– Global Youth Ambassador, European Society for Blood and Marrow Transplantation (EBMT)
Research Grants and Publications:
Dr. Sun has led two projects funded by the National Natural Science Foundation of China and four provincial-level projects, including key R&D programs, Beijing Natural Science Foundation, Beijing Science and Technology Plan, and a special research fund for doctoral programs at higher education institutions under the Ministry of Education. He has authored over 50 papers in Chinese and English as the first author or corresponding author and has received provincial-level awards as a participant on two occasions.
Awards and Honors:
Dr. Sun has been recognized with numerous awards such as the Beijing Excellent Physician Award, the 2021 People’s Good Doctor Youth Model Award, and the Outstanding Young Award at Peking University People’s Hospital.
Research Focus:
Dr. Sun’s research primarily involves clinical and investigative efforts in hematopoietic stem cell transplantation (especially in elderly patients, intractable or relapsed leukemia, myelofibrosis, chronic myelomonocytic leukemia) and hematological diseases with concurrent infectious complications.
