From April 11 to 12, 2025, the Hematology Branch of the China International Exchange and Promotive Association for Medical and Health Care(CPAM) held its annual academic meeting in Qingdao, Shandong Province, alongside the “Hua Tuo Project” MDT Forum. During the event, Academician Xiaojun Huang—Conference Chair, Director of the Hematology Branch of the CPAM , and professor at Peking University People’s Hospital—delivered a landmark keynote titled "50 Years of Hematopoietic Stem Cell Transplantation." His talk provided a comprehensive review across four dimensions: historical development, China’s contributions, advances in immunotherapy, and future perspectives. He highlighted milestone achievements and global impacts—especially the original “Beijing Protocol”—and underscored how Chinese innovations are reshaping the international transplant landscape, offering valuable insights for hematologists worldwide.Tracing the Origins
Breaking Through Barriers: Milestones in Global Transplantation Technology
In 1939, the first bone marrow transplant in human history was performed on a patient suffering from aplastic anemia caused by heavy metal poisoning. With limited knowledge but remarkable courage, clinicians infused bone marrow from the patient’s ABO-compatible brother. Though the attempt ultimately failed, it marked the beginning of the exploration into transplant medicine.
In 1957, Dr. Edward Donnall Thomas in the United States pioneered the modern model of hematopoietic stem cell transplantation (HSCT). Among his first six transplant patients, only one survived beyond 100 days, while the others passed away shortly after treatment[¹]. It wasn’t until 1977 that a major breakthrough occurred: 13 out of 100 patients with relapsed acute leukemia who received HLA-identical sibling allogeneic HSCT (allo-HSCT) achieved long-term survival. Two years later, Dr. Thomas applied this approach during remission, and the two-year survival rate soared from under 15% to 50%. These findings were published in Blood and The New England Journal of Medicine. In 1980, with improved understanding of HLA typing, advancements in antigen identification techniques, and a growing need for transplants, Dr. Thomas successfully performed bone marrow transplants from unrelated HLA-matched donors. This milestone demonstrated the feasibility of unrelated donor transplants, helping to resolve the problem of limited donor availability[²]. These three pivotal achievements cemented Dr. Thomas’s reputation as the “father of hematopoietic stem cell transplantation.”
Around the same time, autologous stem cell transplantation (ASCT) also made significant progress. In 1977, it was successfully applied for the first time in the treatment of relapsed acute myeloid leukemia (AML)[³], and it later expanded to include non-Hodgkin lymphoma and multiple myeloma.
Following these developments, three haploidentical HSCT (haplo-HSCT) approaches for treating acute leukemia emerged:
- The Italian Approach: This technique used ex vivo T cell depletion (TCD) and high-dose CD34+ stem cells. In 1998, Professor Aversa (Italy) and Professor Reisner (Israel) published results in NEJM showing that among 43 patients, the 1.5-year disease-free survival (DFS) for AML was 36% ±11%, while the 2.5-year DFS for acute lymphoblastic leukemia (ALL) was 17% ±7%. Importantly, donor natural killer (NK) cell alloreactivity in the graft-versus-host (GvH) direction helped reduce AML relapse rates and improve survival.
- The “Beijing Protocol”: Developed by Academician Xiaojun Huang’s team at Peking University People’s Hospital, this approach involves bone marrow and peripheral blood transplantation from haploidentical donors without ex vivo T cell depletion, using G-CSF (granulocyte colony-stimulating factor) and ATG (anti-thymocyte globulin) to induce immune tolerance. In 2000, Huang’s team was the first in the world to successfully perform a double cord blood transplant for a high-body-mass patient. That same year, they began developing the mixed bone marrow and peripheral blood transplant protocol without T cell depletion. In a multicenter retrospective study based on data from the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG), the team compared clinical outcomes among the G-CSF/ATG protocol, post-transplant cyclophosphamide (PTCy) protocol, and a combined low-dose ATG + PTCy protocol in patients with hematologic malignancies. Results showed that the G-CSF/ATG regimen led to faster hematopoietic recovery, longer survival, and superior clinical efficacy. By 2013, the number of haploidentical transplants in China surpassed that of HLA-matched sibling donor transplants (MSD-HSCT), with the Beijing Protocol accounting for over 90% of all haplo-HSCTs. Today, the Beijing Protocol is widely adopted in transplant centers across Asia and Europe.
- The “Baltimore Protocol”: Pioneered in 2008 by Johns Hopkins University in the United States, this method employs post-transplant cyclophosphamide (PTCy) for GVHD prevention. The Baltimore Protocol revolutionized haplo-HSCT by achieving acceptable rates of engraftment, GVHD, relapse, and survival. At present, both the Beijing and Baltimore protocols—neither of which require ex vivo T cell depletion—have become mainstream haploidentical transplant strategies worldwide.
The “Beijing Protocol” has demonstrated significant advantages across multiple critical indicators, including neutrophil and platelet engraftment, non-relapse mortality (NRM), overall survival (OS), and leukemia-free survival (LFS). It effectively addresses long-standing challenges such as graft-versus-host disease (GVHD), infection, and relapse. As a result, it has become the preferred haploidentical HSCT (haplo-HSCT) approach for patients with acute leukemia in China.
Pioneering Innovation: Chinese Wisdom Reshaping the Global Landscape of Hematopoietic Therapy
In 1964, Academician Daopei Lu—known as the “Founding Father of Bone Marrow Transplantation in China”—performed Asia’s first and the world’s fourth allogeneic, HLA-identical bone marrow transplantation at Peking University People’s Hospital. This historic breakthrough saved the life of a patient with aplastic anemia and marked the birth of China’s hematopoietic stem cell transplantation (HSCT) program.
In 1981, Academician Lu successfully carried out the country’s first matched sibling donor allogeneic HSCT, which was formally published in 1984[⁴], laying the technical foundation for future developments in the field.
In 1986, Professor Wenwei Yan and his team achieved China’s first successful autologous bone marrow transplantation, an achievement later published in 1998[⁵]. This milestone opened a new chapter in the treatment of hematologic malignancies using autologous HSCT, filling a critical gap in domestic clinical practice.
Since the turn of the 21st century, China’s HSCT field has entered a rapid development phase. In 2000, the country completed its first sibling haploidentical HSCT by inducing immune tolerance through cytokine mobilization. Just two years later, in 2002, the first successful haploidentical transplant from a parent donor was performed.
The creation of the “Beijing Protocol” represented a major breakthrough in China’s HSCT journey. Supported by a national research initiative in 2011, it was the first to demonstrate that haploidentical transplantation offers superior efficacy over chemotherapy in adults with standard-risk acute lymphoblastic leukemia. The establishment of this haploidentical transplant system marked the beginning of a new era—an era in which every patient could have a donor.
Today, the “Beijing Protocol” stands as the most widely implemented haploidentical transplant platform in the world, exemplifying how Chinese innovations are redefining global standards in hematopoietic therapy.
In 2016, the President of the World Marrow Donor Association officially referred to the non–ex vivo T cell-depleted haploidentical hematopoietic stem cell transplantation system developed by Academician Xiaojun Huang’s team as the “Beijing Protocol.” This groundbreaking innovation addressed the global challenge of donor scarcity, transforming haploidentical transplantation into a first-line treatment for leukemia. It established a new global standard for haploidentical transplantation and ushered in a historic new era in which everyone could have a suitable stem cell donor.
Developed by the Peking University team, the “Beijing Protocol” not only overcame the immunologic barriers posed by HLA mismatch and resolved transplant rejection, but also established haploidentical HSCT as a routine procedure at their center. Its indications have expanded beyond malignant diseases to include benign hematologic conditions such as severe aplastic anemia (SAA), hereditary spherocytosis, and inherited metabolic disorders.
Since its introduction, the Beijing Protocol has rapidly spread throughout China. Today, 94% of haploidentical transplants nationwide adopt this protocol. As a result, the number of transplant centers in China rose sharply—from 27 in 2008 to 194 by 2022. As the birthplace of this innovation, Peking University People’s Hospital has seen a steady annual increase in haploidentical transplants, performing over 1,300 hematopoietic stem cell transplants in 2022, including more than 900 haploidentical procedures. This remarkable achievement has made the hospital the largest haploidentical transplant center in the world, consistently maintaining global leadership in both clinical outcomes and technological innovation.
Internationally recognized as a prime example of Chinese medical innovation reshaping global practice, the Beijing Protocol has been included in several authoritative textbooks. Blood magazine noted that the protocol accounts for “half of all haploidentical transplants worldwide.” The fifth edition of Thomas’ Hematopoietic Cell Transplantation—named after Nobel Laureate Dr. Thomas—acknowledges that haploidentical protocols in countries like South Korea and Italy were derived and adapted from the Beijing Protocol with significant clinical success. Szer Jeff and Kodera Yoshihisa, current and former presidents of the World Marrow Donor Association, respectively, have also described the Beijing Protocol as a reliable alternative for patients lacking matched donors.
From domestic success to global adoption, the Beijing Protocol has driven innovation in hematopoietic transplantation while offering new hope to patients worldwide. It stands as a testament to China’s growing influence in medical science. Spearheading this transformative journey, Academician Xiaojun Huang’s team continues to uphold a culture of collaborative innovation, patient-centered care, and research-driven clinical practice—opening new doors of life for patients with hematologic malignancies across the globe.
Integration: A Synergistic Revolution in Immunotherapy and Transplantation
The integration of emerging cellular immunotherapies—especially CD7 chimeric antigen receptor T-cell (CAR-T) therapies—with allogeneic HSCT (allo-HSCT) has unlocked new therapeutic potential. If the Beijing Protocol is seen as a model of clinical-to-translational innovation, CAR-T therapy represents the reverse: from bench to bedside.
In 2012, pioneers of CAR-T cell therapy—Professors Carl H. June, Steven A. Rosenberg, and Michel Sadelain—achieved the first clinical success by treating a child with severe B-cell acute lymphoblastic leukemia (B-ALL), marking the beginning of CAR-T therapy’s clinical era.
In 2014, Professor Weidong Han’s team in China reported the preliminary results of EGFR-targeted CAR-T therapy in cholangiocarcinoma in Clinical Cancer Research[6], marking the nation’s first exploration of CAR-T for solid tumors.
Since then, China has made remarkable progress in CAR-T therapy across target selection, cell engineering, and clinical translation. Several CAR-T products have already been approved, offering new hope for patients with hematologic malignancies.
Notable milestones in recent years include:
- Synthetic TCR-antigen receptor (STAR) therapy for relapsed/refractory B-ALL: A 2012 trial demonstrated that STAR-OX40 T cells are a promising and safe option for B-ALL[⁷].
- CD38 CAR-T for relapsed/refractory AML: In 2021, Dr. Depei Wu and Dr. Xiaowen Tang’s team at The First Affiliated Hospital of Soochow University treated six post-transplant AML patients with CD38-targeted CAR-T, achieving a remission rate above 66.7% with no severe CRS or ICANS observed[⁸].
- Naturally Selected CD7 CAR-T for R/R T-ALL: In 2022, Beijing Lu Daopei Hospital launched the first human trial using naturally selected CD7 CAR-T cells (NS7CAR) from donors or patients—without requiring CD7 gene editing or protein blocking. The therapy proved both safe and effective[⁹].
- Universal CD7 CAR-T Resistant to Rejection: That same year, Professor He Huang’s team at The First Affiliated Hospital of Zhejiang University developed RD13-01—gene-edited, donor-derived CD7 universal CAR-T cells. This became the first global CD7-targeted universal CAR-T to complete a Phase I clinical study, setting a new benchmark in treating refractory CD7+ T-cell malignancies[¹⁰].
- CAR-T + Allo-HSCT Sequential Protocol: In 2024, Professor He Huang’s team further proposed an integrated CAR-T followed by allo-HSCT treatment strategy. This synergy maximizes both the sustained antitumor activity of CAR-T cells and the graft-versus-leukemia (GVL) effect of transplantation—offering a viable option for CD7+ malignancies ineligible for conventional HSCT[¹¹].
According to Academician Xiaojun Huang, while conceptual innovation still lags slightly behind the United States, China has entered a phase of independent, parallel development in application. However, regulatory optimization remains crucial to achieving the goal of universal access to cell therapies.
China’s unwavering pursuit of CAR-T research has led it from a position of following to one of competing, contributing significantly to global advances and expanding therapeutic options for patients. Looking ahead, continued breakthroughs in this field will bring renewed hope to more patients around the world.
Outlook: Intelligence-Driven Precision — A New Era in Hematopoietic Stem Cell Transplantation
In the wave of iterative upgrades in medical technology, precision cell therapy has become an important development direction for the treatment of hematological malignancies in the future. The combination of precision hematopoietic stem cell transplantation and novel cellular immunotherapy is expected to bring more significant therapeutic effects and longer survival periods to patients with hematological malignancies.
In the field of precision hematopoietic stem cell transplantation, optimizing the conditioning regimen is one of the key strategies to improve the transplantation success rate and patient survival rate. Aiming at the special needs of elderly patients and those with complications, researchers have laid a solid foundation for the safety and effectiveness of transplantation by exploring novel drug combinations and dosage regulation strategies. Taking a prospective clinical study [12] conducted by Academician Xiaojun Huang’s team in 2021 as an example, for 50 elderly patients (≥55 years old) with acute leukemia or myelodysplastic syndrome who underwent haploidentical transplantation, a novel reduced- toxicity conditioning regimen of reduced-dose Cy combined with BUFlu+ATG was adopted. The research results showed that the treatment-related mortality (TRM) 1 year after transplantation was 23.3%, the cumulative incidence of relapse (CIR) was 16.5%, the overall survival rate (OS) at 1 year was 63.5%, and the leukemia-free survival (LFS) rate at 1 year was 60.2%. These results were similar to those of patients who received the Bu/Cy/ATG regimen for haploidentical transplantation using the propensity score matching method, demonstrating the feasibility and effectiveness of the novelconditioning regimen in elderly patients undergoing haploidentical transplantation. As for the relapse management post-HSCT , a study in 2023 further confirmed the efficacy of preemptive IFN-α treatment in AML patients with positive minimal residual disease (MRD) after allo-HSCT [¹³] and the use of interventional immunotherapy such as modified donor lymphocyte infusion can effectively prevent the relapse of AML after transplantation.
At the same time, CAR-T cell therapy, as a novel cellular immunotherapy method, has shown great potential. Professor Xi Zhang from The Second Affiliated Hospital (Xinqiao Hospital) of Army Medical University summarized the potential advantages of the combined treatment of CAR-T cell therapy and HSCT in a study in 2022 [¹⁴], providing new ideas for the combined application between traditional curative methods and cutting-edge immunocytotherapy. Subsequent studies have further confirmed that preemptive CAR-T treatment can effectively eliminate minimal residual disease (MRD) of leukemia after transplantation, further highlighting the clinical value of the combined treatment of “transplantation + immunotherapy”.
Today, the deep integration of novel cellular immunotherapy and precision HSCT is propelling patients with hematological malignancies towards a new journey of disease-free long-term survival. In the future, with the continuous innovation of technology and the expansion of clinical applications, this combined treatment model is expected to bring benefits to more patients.
Conclusion
The 50-year evolution of hematopoietic stem cell transplantation (HSCT)—from its inception to maturation—resembles a medical epic, marked by bold challenges and historic breakthroughs. From early experimental attempts to today’s cutting-edge innovations, Chinese-originated advancements such as the “Beijing Protocol” have taken center stage on the global stage, reshaping the trajectory of modern transplantation.
In this wave of technological advancement, the deep integration of targeted therapies and immunotherapies has emerged as a powerful engine, enabling HSCT to deliver sustained, disease-free survival for patients with hematologic malignancies. Building on this foundation, precision cell therapy is rapidly becoming the future frontier—leveraging genomic profiling and immune microenvironment analysis to tailor treatment strategies, thereby further improving long-term outcomes.
Meanwhile, artificial intelligence (AI) and big data are injecting transformative momentum into this medical revolution. By applying machine learning algorithms to analyze data from millions of transplant cases, clinicians can now accurately predict the risk of complications and relapse after transplantation. These insights allow for the dynamic optimization of immunosuppressive regimens, creating a data-driven and intelligently guided decision-making model. What was once theoretical—personalized medicine—is now entering real-world clinical application.
This fusion of technology and medicine is opening expansive new paths for precision HSCT and cell therapy. Looking ahead, as global research and clinical communities unite in pursuit of innovation, breakthroughs across the entire chain—from biotechnological advancement to intelligent clinical support—will continue to push the boundaries of life sciences. Together, they will illuminate new hope for cures and write the next chapter in humanity’s fight against hematologic diseases.
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Academician Xiaojun Huang
Peking University People’s Hospital
Professor Xiaojun Huang is a doctoral advisor, Chief Physician, and Boya Distinguished Professor at Peking University. He serves as Director of the Institute of Hematology at Peking University and Director of the National Clinical Research Center for Hematologic Diseases. He is an Academician of the Chinese Academy of Engineering and a Foreign Academician of the French National Academy of Medicine.
Professor Huang holds several prestigious leadership positions, including Member of the Academic Advisory Board of the Chinese Academy of Medical Sciences, Vice President of the 4th Council of the World Association of Chinese Physicians, and former President of the 4th and 5th Hematology Branch of the Chinese Medical Doctor Association. He is also Chair of the Experimental Hematology Committee of the Chinese Society of Pathophysiology and former Chair of the 9th Hematology Branch of the Chinese Medical Association.
He is the Executive Editor-in-Chief of the Journal of Translational Internal Medicine and serves as Associate Editor for several core journals, including British Journal of Haematology, Journal of Hematology & Oncology, Annals of Hematology, and Chinese Medical Journal. He is also the Editor-in-Chief of the 9th edition of the Chinese Journal of Hematology.
Professor Huang has led numerous national research programs, including the National Key R&D Program, the “863” Program, and major projects under the National Natural Science Foundation of China (NSFC), including Distinguished Young Scholars and Key Projects. He has published 118 SCI papers as corresponding or first author, including in top-tier journals such as The Lancet Oncology (impact factor up to 54.4), with a total of 10,867 citations. He holds 22 authorized patents.
His scientific achievements have earned him two Second-Class National Science and Technology Progress Awards (as first contributor), four First-Class Awards at the provincial or ministerial level, the Ho Leung Ho Lee Science and Technology Progress Award, the Guanghua Engineering Science and Technology Award, and the Distinguished Service Award from the Center for International Blood and Marrow Transplant Research (CIBMTR).
