With the spring breeze of April sweeping through Florence, the 51st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2025) was successfully held from March 30 to April 2, bringing together over 5,000 global experts to explore the latest advances in hematopoietic stem cell transplantation and cellular therapy.
Among the distinguished contributors was Prof. Yue Lu and his team from Hebei Yanda Lu Daopei Hospital, who were selected for both an oral presentation (Abstract No. OS6-04) and a poster presentation (Abstract No. B272)—a testament to the international recognition of their work.
The oral presentation (OS6-04) focused on allogeneic hematopoietic stem cell transplantation in patients with KMT2A-rearranged acute leukemia, highlighting how pre-transplant complete remission (CR) status and early post-transplant molecular minimal residual disease (MRD) monitoring can significantly impact prognosis. These findings provide critical evidence to support precision clinical decision-making.
The poster presentation (B272) further demonstrated that pre-transplant molecular testing and multiparameter flow cytometry serve as independent adverse prognostic factors, offering valuable insights for optimizing clinical monitoring strategies.
Hematology Frontier invited Prof. Yue Lu to share and interpret the clinical significance of these research findings—shining a spotlight on the vital contributions of Chinese scholars in advancing treatment for KMT2A-rearranged acute leukemia and tracing the path forward in transplant-driven cures.
Hematology Frontier: At this year’s EBMT Congress, your team’s research attracted considerable attention, with both an oral and a poster presentation selected. Could you start by walking us through the details of the oral presentation OS6-04?
Prof. Yue Lu: This study, conducted as a single-center report from our hospital, included 455 patients with KMT2A-rearranged acute leukemia (KMT2A-r-AL) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). It represents one of the largest clinical studies to date in this specific patient population.
In terms of remission status before transplantation, 273 patients (60.0%) were in first complete remission (CR1), 98 (21.5%) were in second complete remission (CR2), and 84 (18.4%) had not achieved remission (NR). The five-year overall survival (OS) and leukemia-free survival (LFS) for the entire cohort were both 65%. Further analysis revealed significant prognostic differences among the groups: CR1 patients had five-year OS and LFS rates of 78%, CR2 patients reached 60%, while NR patients had much poorer outcomes at only 34%. Notably, CR1 patients who were MRD-negative prior to transplantation showed even better outcomes, with five-year OS and LFS reaching 83%. These results clearly indicate that patients who achieve remission quickly especially those reaching molecular remission and undergoing allo-HSCT during CR1, derive the greatest benefit.
Under a transplant regimen involving haploidentical donors and busulfan-based myeloablative conditioning, the study also assessed the prognostic impact of different remission statuses. Compared to patients who achieved remission, NR patients had worse outcomes, with higher relapse rates and increased transplant-related mortality. Among patients in remission, those in CR2 with dual MRD positivity—detected by both molecular testing and multiparameter flow cytometry (MFC)had worse outcomes than CR1 patients. Even within the CR1 subgroup, those with MRD positivity prior to transplantation had inferior survival. Additionally, MRD positivity within the first 100 days post-transplant was associated with a higher relapse rate and poorer overall survival.
The study also presented a comprehensive overview of the partner genes and co-occurring genetic mutations associated with this distinct subtype of acute leukemia and their impact on prognosis. In AML, no significant survival differences were observed between patients with RAS pathway mutations or those with different fusion partners such as MLLT3 and AFDN. However, in ALL, patients with AF6 fusion or concurrent TP53 mutations experienced higher relapse rates and poorer survival. Moreover, the presence of hyperleukocytosis at initial diagnosis—defined as peripheral white blood cell count ≥100×10⁹/L—was also an indicator of adverse prognosis. It is worth noting that while age had limited impact on prognosis across the full cohort, in the CR1 subgroup, patients aged one year or younger showed distinctive prognostic patterns. Some findings differed from previous studies, underscoring the marked heterogeneity in outcomes among KMT2A-rearranged leukemia patients.
Hematology Frontier: The OS6-04 study identified several prognostic factors influencing long-term survival before and after transplantation. Based on these findings, what specific advice would you offer clinicians regarding transplant decision-making and post-transplant management?
Prof. Yue Lu: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the most important and effective treatments for KMT2A-rearranged acute leukemia (KMT2A-r AL). Although a number of studies both in China and internationally have explored factors affecting prognosis, the conclusions vary between research centers. These factors include patient age at diagnosis, the type of fusion partner gene, co-occurring genetic mutations, the presence of leukocytosis at diagnosis, complex cytogenetic abnormalities, extramedullary involvement, pre-transplant disease status, and MRD status. Among these, the most widely accepted consensus is that achieving remission before transplant—especially deep remission—is an independent prognostic factor.
To achieve optimal treatment outcomes, it is essential to precisely manage every step of the treatment process. Therefore, initiating individualized therapy at diagnosis and rapidly achieving deep remission becomes critical. Traditional chemotherapy is approaching its efficacy limits, while targeted therapies offer new promise. Among them, menin inhibitors appear to be the most promising, though not yet widely accessible. Other potentially effective targets include FLT3 inhibitors, proteasome inhibitors, hypomethylating agents, histone deacetylase inhibitors, BCL-2 inhibitors, RAS pathway inhibitors, BET inhibitors, and immunotherapies.
Beyond remission induction, precise decision-making throughout the transplant process is equally vital. First, timing is crucial. Numerous studies have demonstrated that undergoing allo-HSCT during first complete remission (CR1) offers patients the greatest benefit. Second, conditioning regimens matter. A recent multicenter study led by Nanfang Hospital of Southern Medical University showed that an intensified conditioning regimen including decitabine (Dec) significantly reduced the three-year cumulative relapse rate in KMT2A-r AL patients (17.6% vs. 34.5%) and improved leukemia-free survival (LFS) (70.1% vs. 56.0%) compared to standard myeloablative conditioning.
Third, donor selection is a key determinant. A 2024 study by the EBMT Acute Leukemia Working Party (ALWP) demonstrated that haploidentical donors (HID) offer stronger graft-versus-leukemia (GVL) effects compared to matched sibling donors (MSD) and matched unrelated donors (MUD), without increasing non-relapse mortality (NRM). The relapse rate was lower in the HID group (39%) compared to MSD (70.6%) and MUD (56.1%), resulting in higher two-year LFS (HID 58.7% vs. MSD 52.8% vs. MUD 43.4%).
Finally, preemptive interventions based on MRD status, such as venetoclax or hypomethylating agent maintenance, can also improve prognosis. Every phase of the treatment journey is interconnected, and only when these components are seamlessly coordinated can we meaningfully improve patients’ disease-free survival.
Looking ahead, future research should focus on: deepening our understanding of the biological features of KMT2A-r AL; exploring individualized combination strategies that integrate traditional and novel targeted therapies; refining MRD-guided precision interventions; and optimizing every stage of the transplantation pathway. Only through such comprehensive efforts can we fundamentally improve outcomes for this challenging and high-risk patient population.
Hematology Frontier: In the B272 study, how does pre-transplant MRD monitoring contribute to improving prognosis in patients with KMT2A-rearranged AML and KMT2A-PTD AML?
Prof. Yue Lu: KMT2A rearrangement is a common molecular abnormality in AML and includes a range of structural changes such as translocations, partial tandem duplications (PTD), deletions, insertions, and inversions. Among these, KMT2A gene translocations are the most frequent, while KMT2A-PTD (also known as MLL-PTD) is relatively rare, accounting for only 3–5% of newly diagnosed AML cases. Patients with KMT2A-rearranged AML typically have a poor prognosis, potentially due to the distinct pathogenic mechanisms associated with different fusion partner genes.
This study analyzed various KMT2A fusion partners and KMT2A-PTD within the AML cohort to identify the optimal MRD monitoring strategy—comparing the clinical utility of multiparameter flow cytometry (MFC) and molecular detection in patients undergoing allo-HSCT during first complete remission (CR1). Currently, KMT2A translocations and KMT2A-PTD are not included as standard molecular MRD markers in clinical guidelines, though accumulating evidence suggests they hold promising prognostic value. In clinical practice, however, it is not uncommon for MFC and molecular MRD assessments to yield discordant results.
Multivariate analysis in this study showed that dual positivity on both MFC and molecular testing was an independent adverse prognostic factor. Patients who were positive on both methods had a significantly higher 5-year cumulative incidence of relapse (CIR) compared to others (23.7% vs. 7.4%), while non-relapse mortality (NRM) remained comparable. As a result, these patients had significantly lower 5-year overall survival (OS) and leukemia-free survival (LFS) (both 54.4% vs. 77.9%), independent of whether MFC or molecular positivity occurred in isolation.
This study suggests that in clinical practice—particularly for patients with definable molecular markers—a multidimensional approach to MRD assessment is necessary. Combining MFC and molecular testing allows for more accurate risk stratification, which is critical for guiding therapeutic decision-making and prognosis evaluation in this high-risk subgroup.
Professor Yue Lu
Hebei Yanda Lu Daopei Hospital
- Chief Physician (Vice President level), Department of Hematopoietic Stem Cell Transplantation, Hebei Yanda Lu Daopei Hospital
- Council Member, Beijing Hematology Society
- Member, Hematopoietic Stem Cell Transplantation Application Group, Hematology Branch of the Chinese Medical Association
- Member, Hematology Committee, Cross-Strait Medical and Health Exchange Association
In October 2016, Professor Lu completed advanced clinical training at the Fred Hutchinson Bone Marrow Transplantation Center in Seattle, USA.
By the end of 2023, she had personally performed over 1,500 allogeneic hematopoietic stem cell transplants.
She has published over 10 SCI-indexed papers in leading journals including Frontiers in Immunology, British Journal of Haematology, Bone Marrow Transplantation, and Biology of Blood and Marrow Transplantation.
