Editor's Note: The “Gaobo Medical Forum—6th Clinical Application Seminar and Training Course on Autologous Hematopoietic Stem Cell Transplantation,” hosted by the National Clinical Research Center for Hematologic Diseases of the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and organized by Shanghai Zhaxin Hospital/Gaobo Medical Group and Shanghai Liquan Hospital, was held in Shanghai on August 29–30, 2026. During the meeting, Oncology Frontier – Hematology Frontier invited Dr. Shan Shao, Medical Team Leader at Gaobo Shanghai Zhaxin Hospital, to systematically discuss alternative treatment strategies for patients intolerant to calcineurin inhibitors (CNIs), drawing on the center's extensive clinical experience, and to share emerging explorations of anti-CD25 monoclonal antibodies as alternatives to CNI and short-course methotrexate (MTX) for GVHD prophylaxis.Oncology Frontier – Hematology Frontier: You have long been engaged in the diagnosis and treatment of hematologic malignancies as well as autologous and allogeneic hematopoietic stem cell transplantation, and have accumulated extensive experience in managing transplant-related complications. Based on your clinical experience, what are the key challenges currently facing GVHD prevention and management after allogeneic transplantation? Which aspects should receive particular attention in clinical practice?
Dr. Shan Shao: In recent years, numerous novel agents have emerged for the prevention and treatment of GVHD following allogeneic hematopoietic stem cell transplantation, including ruxolitinib and anti-CD25 monoclonal antibodies. These novel agents have significantly improved the clinical management of GVHD to some extent. Nevertheless, conventional agents represented by calcineurin inhibitors remain irreplaceable and continue to play a central role; they are still the cornerstone of GVHD prevention and treatment in clinical practice.
In clinical practice, second-line agents are generally introduced when treatment regimens need to be adjusted because of changes in a patient’s condition. The major challenge we face is that calcineurin inhibitors are associated with certain toxicities and adverse effects. In particular, some high-risk or refractory patients are unable to tolerate CNIs because of organ dysfunction or unstable vascular endothelial function, and may even require discontinuation because of severe toxicities. In such circumstances, there is an urgent clinical need for second-line alternative agents with better efficacy and safety.
In addition, infection control remains a major challenge in the comprehensive management of GVHD. Although an increasing number of immunosuppressive agents are now available, immune reconstitution after transplantation remains incomplete. When worsening GVHD necessitates intensification of immunosuppressive therapy, the risk of severe infection increases substantially. Therefore, how to better balance immunosuppression with infection control remains a major challenge, and we hope that more optimized treatment strategies will emerge in the future.
Oncology Frontier – Hematology Frontier: You previously conducted a study investigating anti-CD25 monoclonal antibody as an alternative to CNI for the prevention of acute GVHD (aGVHD) after transplantation. How do you assess the value of alternative therapy for patients who are intolerant to CNI or require discontinuation because of CNI-related toxicity? What issues should receive particular attention in clinical practice?
Dr. Shan Shao: The patients treated at our center have certain distinctive characteristics, with many having received multiple lines of prior therapy. Some have previously undergone autologous or allogeneic hematopoietic stem cell transplantation and experienced repeated cycles of radiotherapy and chemotherapy, resulting in poor organ reserve and unstable vascular endothelial function. Consequently, these patients are not only highly susceptible to various complications during transplantation but also generally have poor tolerance to calcineurin inhibitors (CNIs).
Particularly during the early post-transplant period, once CNI intolerance develops, patients face not only a very high risk of severe acute GVHD (aGVHD) but may also develop severe organ dysfunction or even early death if CNI therapy is continued. Therefore, we hope to use safe and effective alternative agents during the early post-transplant period. Although previous attempts have been made to use agents such as ruxolitinib and sirolimus as alternatives, there remains an unmet clinical need.
Against this background, our center has explored the use of anti-CD25 monoclonal antibody as an alternative to CNI. When patients develop severe renal dysfunction, central nervous system abnormalities, or vascular endothelial injury syndrome (VES) during the early post-transplant period, we temporarily discontinue CNI and administer anti-CD25 monoclonal antibody once weekly as an alternative therapy. Our findings showed that this strategy could help patients safely navigate the most challenging phase of the early post-transplant period. Once the patient’s condition stabilizes, CNI therapy can be reintroduced, thereby facilitating the successful continuation of transplantation.
Subsequent follow-up further showed that this alternative treatment strategy did not result in a significant increase in the incidence of aGVHD, and no fatal GVHD occurred. Therefore, we believe that anti-CD25 monoclonal antibody replacement therapy has a favorable safety and efficacy profile and represents an important direction worthy of further investigation.
Oncology Frontier – Hematology Frontier: With the continued development of transplantation techniques and immunotherapy, GVHD prophylaxis strategies are also being continuously optimized. Based on your research and clinical experience, could GVHD prophylaxis become more individualized in the future? What other potential applications of novel immunomodulatory agents such as anti-CD25 monoclonal antibodies are worth exploring?
Dr. Shan Shao: As a cornerstone of GVHD prophylaxis, CNI therapy currently maintains an unshakable position in clinical research and practice. Based on the available clinical data, patients who can tolerate CNI should still receive adequate and effective CNI therapy. At present, there is no evidence from clinical studies supporting the direct replacement of CNI with novel agents at the initial stage. However, being a cornerstone therapy does not mean that CNI cannot be adjusted. For patients who are unable to tolerate CNI for specific reasons but urgently require transplantation, anti-CD25 monoclonal antibody replacement therapy may provide a new pathway that could enable transplantation to proceed.
In addition, the “CNI plus short-course methotrexate (MTX)” regimen widely used at transplant centers remains a classic GVHD prophylaxis strategy. However, in clinical practice, we have found that MTX itself has a certain degree of mucosal toxicity. This is particularly relevant when patients have already received conditioning regimens containing high-dose total body irradiation (TBI) or thiotepa, both of which can cause mucosal toxicity. Adding short-course MTX may further aggravate mucosal injury and, consequently, significantly increase the risk of infection during treatment because of mucosal ulceration.
Based on this consideration, our center is currently exploring a strategy in which anti-CD25 monoclonal antibody (Jenycap) is administered on day 4 after transplantation as a substitute for MTX. Preliminary observations suggest that this replacement strategy can indeed improve mucosal injury in patients. Of course, the final clinical data still need to be validated through continued patient enrollment and follow-up. We look forward to obtaining more favorable long-term outcomes.
Expert Profile
Dr. Shan Shao
Gaobo Shanghai Zhaxin Hospital
- Deputy Chief Physician, MD; Medical Team Leader at Gaobo Shanghai Zhaxin Hospital
- Former Attending Physician at Shanghai General Hospital; graduated from Shanghai Jiao Tong University School of Medicine and obtained a doctoral degree
- Visiting Scholar at the Stowers Institute for Medical Research, USA, in 2018
- Has published multiple articles in well-known professional journals in China and abroad
- Participated in several projects funded by the National Natural Science Foundation of China and served as Principal Investigator of one National Natural Science Foundation of China Young Scientists Fund project
- Areas of expertise: Diagnosis and treatment of hematologic malignancies; responsible for the treatment and management of patients following allogeneic hematopoietic stem cell transplantation
