-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4998 Gene Therapy of Transfusion-Dependent β-Thalassemia Patients with Quick Engraftment of Reinfused Hematopoietic Stem Cells: An Investigator-Initiated Trial of KL003Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 801. Gene Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research, Genetic Disorders, drug development, pediatric, Diseases, Therapies, young adult , Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Jinqi Huang1*, Yuming Zhang, M.D.1*, Liang Liang, M.D.1*, Jiayuan Wu, Ph.D.1*, Xiaoqian Li, M.D.1*, Zhonglu Ye1*, Bin Lin1*, Jingzhi Ma1*, Lingling Su2*, Qing Ye2*, Jianan Sun2*, Zhengliang Wang2*, Baozhen Sun2*, Xiaodong Hu2*, Peng Lv2*, Jianjun Tao2*, Ying Dang2*, Depei Wu, M.D.1, Youren Tong2* and Haoquan Wu2*

1Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
2Kanglin Biotech (Hangzhou) Co., Ltd., Hangzhou, China


In recent years, autologous hematopoietic stem cell (HSC)-based gene therapy has emerged as one of the most promising curative therapies for the treatment of severe hereditary anemia, including β-thalassemia major. Although several clinical trials of gene therapy for β-thalassemia major patients have been completed in developed countries, clinical data of gene therapy remain scarce for patients in developing countries. These patients are often in poor clinical condition because of severe iron overload and insufficient blood transfusion due to limited blood supply. They account for the majority of the β-thalassemia major patients in developing countries. Unlike in developed countries, most β-thalassemia major patients in developing countries cannot survive to adulthood as a consequence of irregular treatments due to the limitation of medical facilities and/or personal financial conditions.


We conducted a non-randomized, single-dose, open-label investigator-initiated clinical trial (ChiCTR2200055565) in representative patients in southern China, including those with ferritin above 5000 µg/L. Among the 11 β-thalassemia major patients (aged 6-22) we enrolled, 6 of the patients were in poor clinical conditions (e.g., medium (3000-5000 µg/L ferritin) to severe (>5000 µg/L ferritin) iron overload) due to inconsistent blood transfusions and iron chelation therapy before enrollment (Table). We treated patients using their own HSCs after transduced ex vivo with KL003, a lentiviral vector expressing a functional β-globin gene. We then monitored patients closely for safety and evaluated efficacy of KL003, including stem cell engraftment, hematopoietic reconstitution/recovery, and blood transfusion requirement.


Blood transfusion was no longer needed for all 11 patients from median day 14 (range: 10-30 days) after treatment. The longest duration of no blood transfusion has been 18 months. The median engraftment time was 14 days for neutrophils (range: 8-15 days) and 14 days (range: 11-33 days) for platelets. This is a significant improvement compared with much longer engraftment time from previous autologous HSC-based gene therapies in the literature, which were around 4 weeks for neutrophils and 6 weeks for platelets. It is worth noting that the platelet engraftment time (33 days) for patient No. 07, who had a severe iron overload, was much longer than others (Table). This may represent a common challenge for treating patients with severe iron overload.

The safety profile was consistent with that typical of busulfan-based myeloablation conditioning. There were no severe adverse events associated with KL003.


Our clinical trial results demonstrate potentially curative results in β-thalassemia major patients, including those in poor clinical condition. In addition, the optimized transduction process of HSCs may have contributed to maintaining stemness of HSCs, which is essential for quick engraftment and often gets lost during ex vivo manipulation. This has led to significantly faster engraftment and better efficacy. Thus, KL003 could be a potential functional cure for β-thalassemia major patients.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH