From December 7–10, 2024, the 66th Annual Meeting of the American Society of Hematology (ASH) was held in San Diego, bringing together global experts and scholars in hematology for an in-depth exploration and exchange of the latest research progress in the field. At this conference, two studies by Dr. Sizhou Feng's team from the Institute of Hematology & Blood Diseases Hospital (Chinese Academy of Medical Sciences) were included for poster presentation (P2127, P2828). "Hematology Frontier" specially invited Dr. Feng to share the research findings and their clinical significance with colleagues at the ASH venue as soon as possible.

1. Improved Preconditioning Regimen with Lipo-MIT for Refractory/Relapsed AML

Hematology Frontier: In your recent study, you evaluated a preconditioning regimen based on liposomal mitoxantrone (Lipo-MIT) combined with busulfan and cyclophosphamide for refractory/relapsed AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Could you elaborate on the improvements of this regimen compared to traditional approaches? What potential applications does this regimen hold for enhancing outcomes and quality of life for AML patients?

Professor Feng: Refractory/relapsed acute myeloid leukemia (AML) patients generally face poor prognoses with limited treatment options. For those with suitable donors, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often considered a viable option. However, even with this intervention, survival rates remain low. Therefore, developing safer and more effective preconditioning regimens to reduce relapse risk and improve clinical outcomes is an urgent need.

In our earlier research, the Lipo-MIT-based combination chemotherapy demonstrated significant remission rates in refractory/relapsed AML patients, including those who relapsed post-allo-HSCT. Building on this foundation, we optimized the preconditioning regimen by incorporating Lipo-MIT into allo-HSCT protocols.

Key Advantages of Lipo-MIT Regimen:

1. Enhanced Safety: The liposomal formulation reduces mitoxantrone’s toxicity.
2. Improved Antitumor Efficacy: Liposomes enhance drug penetration and retention at tumor sites.
3. Reduced Side Effects: The regimen is better tolerated compared to conventional formulations.

We integrated Lipo-MIT into the standard busulfan (Bu) and cyclophosphamide (Cy) preconditioning regimen for:

• Refractory/relapsed AML patients.
• Minimal residual disease (MRD)-positive cases.
• Advanced myelodysplastic syndrome (MDS) patients.

Outcomes:

• Overall Survival (OS): 95.2%.
• Relapse-Free Survival (RFS): 83.9%.

These findings underscore the significant improvements in transplant efficacy, enhanced survival rates, and improved quality of life. This innovative regimen holds great promise for broader clinical applications, benefiting high-risk AML patients.

2. Blinatumomab as Maintenance Therapy Post-Allo-HSCT for High-Risk B-ALL

Hematology Frontier: Another of your studies explored blinatumomab as a post-allo-HSCT maintenance therapy for high-risk B-ALL patients. What clinical guidance does this research offer for treatment planning? What opportunities and challenges does this therapy face in future applications?

Professor Feng: Relapse remains a significant challenge for acute lymphoblastic leukemia (ALL) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Blinatumomab has emerged as a promising solution, addressing this challenge through its dual roles:

1. Pre-transplant Bridging Therapy: Facilitates successful allo-HSCT by reducing disease burden.
2. Post-remission Maintenance Therapy: Prevents relapse by targeting residual leukemia cells.

In MRD-positive B-ALL patients, the risk of post-allo-HSCT relapse is particularly high, making blinatumomab’s role critical. By eradicating residual leukemia cells, it promotes deeper remission both before and after transplantation.

Study Findings: We followed 11 high-risk B-ALL patients undergoing one year of maintenance therapy with blinatumomab post-allo-HSCT:

• Only one patient experienced molecular relapse.
• The remaining patients maintained sustained remission.

These results suggest that blinatumomab is effective in reducing relapse rates post-allo-HSCT, thereby improving patient survival.

Opportunities and Challenges:

• Opportunities: Expanding the use of blinatumomab in maintenance therapy could provide significant clinical benefits, particularly for high-risk cases.
• Challenges: Future research must address patient selection criteria, optimal dosing and duration, and accessibility to ensure broader adoption.

Blinatumomab’s integration into post-transplant care represents a promising advance in leukemia treatment, offering improved outcomes for high-risk patients.

03: Future Directions in Leukemia Treatment and Key Challenges

Hematology Frontier: What are your expectations for the future of leukemia research, and what critical issues and challenges must be addressed in upcoming studies?

Dr. Sizhou Feng: The rapid advancements in targeted therapy and cellular immunotherapy have paved new paths for leukemia treatment. These innovative approaches are revolutionizing the field in multiple ways:

1. Targeted Therapies: Third-generation tyrosine kinase inhibitors (TKIs), in combination with bispecific antibodies or CAR-T cell therapies, offer unprecedented treatment potential for leukemia patients. These therapies may enable some patients to achieve curative outcomes without undergoing the complex process of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
2. New Opportunities in Autologous Stem Cell Transplantation (Auto-HSCT): For many leukemia patients, these advancements have introduced the possibility of leveraging auto-HSCT as a viable treatment option. By significantly reducing or completely eliminating residual leukemia cells, patients can achieve remarkable therapeutic outcomes through autologous transplantation. Auto-HSCT offers distinct advantages in preserving patient quality of life. Optimizing this strategy not only increases survival opportunities but also enhances overall well-being.
3. Preconditioning Optimization: The inclusion of novel targeted therapies in preconditioning regimens aims to further optimize therapeutic outcomes. These drugs expand the range of available preconditioning options while paving the way for more effective post-transplant maintenance strategies, solidifying the overall treatment efficacy.

Summary

Dr. Sizhou Feng’s team has achieved significant progress in leukemia treatment through improved preconditioning regimens and the exploration of novel maintenance therapies. These innovative approaches provide leukemia patients with more effective treatment options, reducing relapse rates and markedly improving survival outcomes and quality of life.

Future Outlook: With the continuous development of targeted and cellular immunotherapies, the leukemia treatment landscape is poised for further breakthroughs. These advancements promise not only more effective solutions but also greater hope for patients worldwide.

Dr. Sizhou Feng

Chief Clinical Specialist, Chinese Academy of Medical Sciences Hematology Hospital (Institute of Hematology, CAMS)

• Academic and Professional Credentials: Doctor of Medicine, Senior Chief Physician Supervisor for PhD and postdoctoral researchers Renowned as one of Tianjin’s “First Distinguished Doctors” Member of the 17th and 18th Tianjin Municipal People’s Congress
• Professional Training and Experience: Postdoctoral research at The University of Tokyo, Japan (July 1999 – July 2001)
• Current Roles: Chief Specialist in Hematopoietic Stem Cell Transplantation and Infection at the Hematology Hospital, Chinese Academy of Medical Sciences Vice Chairman, Pharmacogenomics Branch of the Chinese Pharmacological Society Vice Chairman, Precision Diagnosis and Treatment of Hematologic Diseases Branch, Chinese Research Hospital Association Deputy Leader, Anti-Infection Group of the Hematology Branch, Chinese Medical Association Member, Committee for Prevention and Control of Bacterial Infections and Antimicrobial Resistance, Chinese Medical Association Standing Member, Invasive Fungal Disease Committee, Chinese Medical Education Association Member, Transplant Immunology Branch, Chinese Society for Immunology Standing Member, Hematology Branch, Chinese Society of Gerontology and Geriatrics Standing Member, Anti-Leukemia Alliance, Chinese Society of Clinical Oncology (CSCO) Chairman, Geriatric Oncology Professional Committee, Tianjin Anti-Cancer Association
• Editorial Roles: Editorial Board Member: Chinese Journal of Organ Transplantation Chinese Journal of Infection and Chemotherapy Clinical Hematology Journal Journal of Clinical Internal Medicine Journal of Acute and Critical Care Medicine
• Publications and Achievements: Published over 50 SCI papers as corresponding author or first author in top journals, including: Journal of Infectious Diseases (Impact Factor 38.6) Clinical Infectious Diseases (Impact Factor 20.999) Nature Communications (Impact Factor 16.6) Clinical Microbiology and Infection (Impact Factor 14.2) British Journal of Haematology (Impact Factor 8.6) Recipient of 7 provincial and ministerial-level scientific and technological progress awards Awarded the Tianjin May 1st Labor Medal Honored as Tianjin’s Most Trusted Physician by Patients

Professor Feng has made groundbreaking contributions to the fields of hematopoietic stem cell transplantation and infection management, positioning himself as a leading expert in hematology and oncology in both clinical practice and academic research.