Editor’s Note: From December 7 to 10, 2024, the 66th Annual Meeting of the American Society of Hematology (ASH) was held in San Diego, USA. Experts and scholars from around the globe gathered to discuss and exchange insights on the latest research in hematology. During the conference, Dr. Bing Han from Peking Union Medical College provided an on-site review of two significant studies from the Severe Aplastic Anemia Working Party (EBMT-SAAWP) of the European Society for Blood and Marrow Transplantation. Professor Han also shared in-depth analyses of key research topics presented at the meeting. These highlights are summarized below for our readers.

01: Advances in Aplastic Anemia

Dr. Bing Han: This year’s ASH meeting showcased remarkable progress in the field of aplastic anemia, particularly in the clinical applications of thrombopoietin receptor agonists (TPO-RAs). Despite their widespread use in clinical practice, prospective or large-scale studies on TPO-RAs remain limited.

During the conference, we observed significant developments in the treatment of severe aplastic anemia (SAA), including updates on eltrombopag, a classic TPO-RA, with long-term follow-up data. Additionally, impressive results were reported for hetrombopag and avatrombopag across multiple studies. For chronic aplastic anemia (CSA), retrospective data and small-sample studies offered new perspectives and considerations.

In the transplantation domain, the comparative efficacy of TPO-RA combination therapies with different types of transplants emerged as a research hotspot. The conference highlighted the outcomes of various transplant types, including matched sibling, haploidentical, and unrelated donor transplants. Synthesizing these studies, matched sibling transplantation remains the preferred approach for severe aplastic anemia, while other donor sources serve as alternatives. This aligns with previous understandings, but the robust evidence provided at ASH reinforces these conclusions. Furthermore, the conference delved deeply into transplantation strategies for diseases like paroxysmal nocturnal hemoglobinuria (PNH), providing valuable insights.

On the basic research front, current investigations focus on the hematopoietic microenvironment and potential key targets. However, these cutting-edge studies have yet to translate into groundbreaking clinical advancements. We hope to see more promising results in the future, paving new paths for the treatment of aplastic anemia and related hematologic disorders.

O302: Final 2-Year Analysis of the EBMT-SAAWP RACE Study: Improved Long-Term Outcomes with Eltrombopag Combined with Standard Immunosuppressive Therapy for Severe Aplastic Anemia

Dr. Bing Han: The RACE study (NCT02009747) is a two-year, prospective, randomized, phase III trial comparing the long-term outcomes of standard immunosuppressive therapy (IST: antithymocyte globulin [ATG] + cyclosporine A [CSA]) with or without eltrombopag (EPAG) as first-line treatment for severe aplastic anemia (SAA). Initial analyses showed that the triple therapy significantly improved hematologic response rates and quality of life, with higher complete response rates (CRR) and objective response rates (ORR) at 3 and 6 months.

The study enrolled 197 treatment-naïve SAA patients who were randomized to receive standard IST (Group A; n=101) or standard IST with EPAG (Group B; n=96) at a dose of 150 mg/day from day 14 to 6 months (or 3 months if complete remission was achieved earlier). Endpoints included overall survival (OS), disease-free survival (DFS, defined as absence of death, lack of response at 6 months, myeloid malignancies, relapse, or transplantation), and event-free survival (EFS, defined as DFS plus initiation of new SAA treatment).

During the follow-up, five patients withdrew early, and 22 deaths were recorded (14 in Group A, 8 in Group B) due to complications related to SAA, such as infections and bleeding. Ultimately, 170 patients completed the two-year follow-up, with a median follow-up duration of 24 months (21.4–28.1 months). In Group A, the 2-year OS was 86.0% (95% CI: 79.2%–92.8%), while in Group B, it was 91.4% (95% CI: 85.8%–97.1%). Multivariable analysis (MVA) revealed that disease severity significantly influenced OS, with a hazard ratio (HR) for Group B of 0.54 (95% CI: 0.28–1.04, P=0.064).

The 2-year DFS in Group B was 54.7% (95% CI: 44.7%–64.7%) compared to 36.6% (95% CI: 27.2%–46.0%) in Group A. The treatment effect was most pronounced during the first year, with an average HR of 0.50 (95% CI: 0.38–0.66, P<0.001). Significant differences were observed between 0–6 months (HR=0.41) and 6–12 months (HR=0.61). Both age and disease severity affected DFS outcomes.

The 2-year EFS in Group B was 48.4% (95% CI: 38.4%–58.5%), whereas in Group A, it was 32.7% (95% CI: 23.5%–41.8%, P<0.001). MVA showed that the treatment effect diminished after 12 months, with age being the only significant factor influencing EFS.

Cumulative relapse rates were similar between the two groups, with a 2-year relapse rate of 22.7% (95% CI: 12.9%–32.6%) in Group B and 18.0% (95% CI: 6.7%–29.3%) in Group A (adjusted HR=1.05, 95% CI: 0.87–1.27, P=0.60). The risk of clonal evolution was negligible, with one case of cytogenetic abnormality in Group A and two cases in Group B. The 2-year cumulative incidence of paroxysmal nocturnal hemoglobinuria (PNH) was significantly lower in Group B at 1.1% (95% CI: 0%–3.2%) compared to 8.1% (95% CI: 2.7%–13.5%) in Group A (adjusted HR=0.12, 95% CI: 0.04–0.33, P<0.001).

This study demonstrated that adding EPAG to standard IST improved hematologic response rates and significantly enhanced 2-year OS, DFS, and EFS without increasing the risk of secondary myeloid malignancies. Although longer follow-up is needed to confirm the curative potential of this triple therapy, the current findings strongly support its use as the first-line treatment for adult SAA patients who are ineligible for hematopoietic stem cell transplantation.

O305: Improved Prognosis of PNH Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation from 2011 to 2020: A Retrospective EBMT-SAAWP Study

Dr. Bing Han: In the era of complement inhibitors, there is limited research on the outcomes of paroxysmal nocturnal hemoglobinuria (PNH) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Earlier studies reported survival rates of less than 70%. This retrospective study, conducted by the Severe Aplastic Anemia Working Party (SAAWP), analyzed the clinical outcomes of PNH patients who underwent HSCT between 2011 and 2020. The analysis included information on associated underlying diseases, HSCT details, transplant outcomes, engraftment rates, graft-versus-host disease (GVHD), overall survival (OS), and event-free survival (EFS).

Between 2011 and 2020, a total of 240 PNH patients received HSCT at 125 EBMT transplant centers. The median age of the patients was 26.4 years (IQR: 18.6–37.2 years), with a median time from diagnosis to transplantation of 10.3 months (IQR: 4.8–34.7 months) and a median follow-up duration of 2.9 years.

The donor sources included HLA-matched sibling donors (MSD; 46.7%), matched unrelated donors (MUD; 37.1%), mismatched unrelated donors (MMUD; 12.9%), and haploidentical donors (Haplo; 3.3%). Stem cell sources were bone marrow (45.8%) and peripheral blood (52.9%). Reduced-intensity conditioning (RIC) regimens were used in 76.6% of patients, while 23.4% received myeloablative conditioning (MAC). GVHD prophylaxis involved calcineurin inhibitors (CNI; 23.7%) or serotherapy (antithymocyte globulin 67.8%, alemtuzumab 3.4%) or post-transplant cyclophosphamide (PTCy, 5.1%).

The cumulative neutrophil engraftment rate by day 28 was 87%, with a median engraftment time of 18 days (16–19 days). The cumulative platelet engraftment rate by day 60 was 85%, with a median engraftment time of 22 days (18–24 days). The 3-year OS was 79%, with infection and GVHD as the leading causes of mortality. Donor type and patient age significantly influenced survival rates. The 3-year OS was 86% for MSD, 78% for MUD, and 62% for MMUD (P=0.003). Among age groups, patients under 20 years had a 3-year OS of 83%, those aged 20–40 years had 82%, and those over 40 years had 67% (P=0.047). The interval from diagnosis to transplantation also affected OS (84% for <1 year vs. 73% for >1 year; P=0.036), while conditioning regimen, comorbidity index (HCT-CI), stem cell source, and GVHD prophylaxis did not show significant impact.

Acute GVHD (grade II–IV) occurred in 14% of patients, with rates of 12% for MSD, 10% for MUD, and 28% for MMUD (P=0.046). Chronic GVHD occurred in 13% of patients, with rates of 15% for MSD, 5% for MUD, and 25% for MMUD (P=0.06). The 3-year GVHD-free relapse-free survival (GRFS) was 66%, with rates of 74% for MSD, 65% for MUD, and 46% for MMUD. Primary (30-day) and secondary (3-year) graft failure rates were 8% and 6%, respectively. Donor type significantly affected primary graft failure (MSD 2%, MUD 14%, MMUD 3%; P<0.001), but not secondary graft failure. Stem cell source influenced secondary graft failure (bone marrow 10%, peripheral blood 3%; P=0.008).

The 3-year EFS was 69%, with donor type (MSD 80%, MUD 65%, MMUD 54%; P=0.006) and the interval from diagnosis to transplantation (<1 year 76% vs. >1 year 61%; P=0.015) being the primary influencing factors. Conditioning regimen, patient age, HCT-CI, stem cell source, and GVHD prophylaxis did not significantly impact EFS.

Among the eight patients who underwent haploidentical HSCT (Haplo-HSCT), four experienced graft failure, one died, and two required salvage HSCT. Two patients developed acute GVHD, and one developed chronic GVHD, which led to death. Three patients survived without GVHD or relapse.

In summary, over the past decade, the prognosis of PNH patients undergoing HSCT has significantly improved, particularly among younger patients using HLA-matched donors (both related and unrelated). The outcomes of RIC regimens were comparable to those of MAC regimens. While complement inhibitors remain the standard treatment for hemolytic PNH, allogeneic HSCT may be considered a viable alternative in cases where complement inhibitors are inaccessible or in specific clinical scenarios.

Dr. Bing Han

Peking Union Medical College

• Chief Physician, Department of Hematology
• Doctoral Supervisor
• Head of the Red Blood Cell Disorders Group, Peking Union Medical College
• Core Member of the International PNH Interest Group (IPIG)
• Vice Chair, Red Blood Cell Disorders Group, Chinese Society of Hematology
• Chair, PNH Subgroup, Rare Diseases Section, Chinese Society of Hematology
• Vice Chair, Academic Committee on Red Blood Cell Disorders, Chinese Geriatrics Society
• Vice Chair, MDS/MPN Working Group, Chinese Anti-Cancer Association
• Vice Chair, MDS Disease Group, Chinese Medical Women’s Association
• Vice Chair, Red Blood Cell Disorders Committee, Beijing Cancer Prevention Society
• Vice Chair, Cytomorphology Committee, Bethune Spirit Research Association
• Vice Chair, Diagnostic Committee on Red Blood Cell Disorders, Chinese Medical Doctor Association
• Standing Committee Member, Geriatric Hematology Branch, Chinese Medical Association
• Executive Council Member, World Federation of Chinese Medicine Societies
• Member, Beijing Rare Disease Society