Editor’s Note: Hematopoietic stem cell transplantation is a common and effective treatment in the field of hematology. As techniques have matured, stem cell transplantation not only serves as a treatment for malignant blood diseases such as leukemia but also offers a new solution for curing thalassemia. The 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting took place in Glasgow, UK, from April 14th to 17th, 2024. The conference highlighted the latest advancements in stem cell transplantation and cellular therapies, pushing hematologic patients towards better clinical outcomes. At this meeting, Professor Li Chunfu from the Gaobo Medical (Hematology) Guangdong Research Center and Southern Chunfu (Children’s) Hematology Institute delivered an excellent oral presentation on the modified TCRαβ-T cell depleted hematopoietic stem cell transplantation (TDH) for treating severe thalassemia. “Oncology Frontier – Hematology Frontier” invited Professor Li to share his insights and experiences regarding transplantation treatments for thalassemia with our readers.
Oncology Frontier – Hematology Frontier: Could you introduce us to the research background and main results you presented at the conference?
Professor Li Chunfu: Our team has been dedicated to overcoming the challenges of thalassemia transplantation for many years, gaining experience and identifying several issues along the way. In 2012, we published a study in Blood on unrelated donor hematopoietic stem cell transplantation for thalassemia, which achieved good therapeutic effects but could only address the needs of a portion of patients; nearly half could not find suitable donors. Haploidentical transplantation became essential to ensure everyone has a potential donor.
Currently, there are various protocols for haploidentical transplantation, including China’s “Beijing Protocol,” the American PTCy protocol, and Europe’s ex vivo T-cell depletion protocol. Initially, we used the PTCy protocol, but encountered several issues, necessitating improvements. We added umbilical cord blood infusion on Day 6, creating a complementary transplantation approach, which we presented at the American Society of Hematology (ASH) meeting. However, we were still not achieving satisfactory outcomes; nearly 50% of the transplants were with cord blood, which often matches at only 7/10 to 8/10 HLA types, sometimes even 6/10. This mismatch led to graft-versus-host disease (GVHD), especially chronic GVHD, which is quite common. Given that thalassemia is a benign condition where patients can live long and maintain quality of life with transfusions and iron chelation, severe chronic GVHD from transplantation is a significant loss. Therefore, finding a safer and more effective transplantation method was imperative.
We then tried the European ex vivo T-cell depletion protocol, known as TCRαβ-T cell depleted hematopoietic stem cell transplantation (TDH). Removing T cells ex vivo prevents GVHD, but T cells also promote engraftment and induce GVHD. Initially, our failure rate was nearly 30%, a significant setback that made us question the viability of this approach. However, after continuous trials, we found that adding cyclophosphamide (CTX) on Day 1 significantly improved outcomes, achieving cure rates over 94%, but still not ideal—we aim for at least 98-99%. We are continuing to make adjustments, having already eliminated total body irradiation (TBI) from the protocol, and we might consider adding donor lymphocyte infusion (DLI) or anti-thymocyte globulin (ATG) in the future.
Ultimately, our goal with hematopoietic stem cell transplantation for benign thalassemia is to ensure a good disease-free survival, curing the primary disease without transplant-related complications.
Oncology Frontier – Hematology Frontier: During the Q&A session, what were some highlights or insights?
Professor Li Chunfu: In the Q&A session, international experts were particularly interested in how ATG was used and why it was removed during the second transplantation. In reality, we used the PTCy protocol for the second transplant. This post-PTCy approach provides good engraftment but poses a risk of secondary tumors. Additionally, the session chair raised questions about COVID-19, which caused viral infections that led to a patient’s death in our study. Had the patient not contracted COVID-19, the clinical outcome might have been better. We found that COVID-19 can cause a decrease in CD4+ cells. It’s merely a contributing factor, not the direct cause of death. Thus, we are confident in our ability to increase the cure rate to 98% in the future.
Oncology Frontier – Hematology Frontier: Could you share the future directions for your research and team?
Professor Li Chunfu: Our future research will focus on further reducing toxicity, particularly concerning fertility issues in patients. As the cure rate for thalassemia continues to improve, a large number of pediatric patients survive and soon enter puberty, posing significant social challenges. We have already completed over 1000 cases. These children will need to integrate into society, so our goals are to reduce mortality and transplant-related complications and to preserve their fertility, enabling them to lead genuinely healthy lives.
Expert Profile
Professor Li Chunfu
Director of Gaobo Medical (Hematology) Guangdong Research Center and Southern Chunfu (Children’s) Hematology Institute
Leader in pediatric hematology and oncology, and hematopoietic stem cell transplantation at Gaobo Medical (Hematology) Research Center
Former Head of Pediatrics, Professor, and Graduate Advisor at Southern Medical University, Nanfang Hospital
Member of the American Society of Hematology
Member of the Chinese Hematopoietic Stem Cell Transplantation Group
Member of the National Children’s Medical Center Alliance for Hematology/Oncology
