Editor’s Note: The 13th Lu Daopei Hematology Forum, jointly organized by the Beijing Health Promotion Association and the Guangzhou Hongmian Cancer and Rare Disease Foundation and hosted by the Beijing Lu Daopei Institute of Hematology, was held in Beijing on August 22–23, 2025. The event gathered leading global experts in hematology to discuss hematopoietic stem cell transplantation (HSCT), cellular therapy, and precision management of hematologic malignancies, offering an exceptional academic experience to over a thousand attendees. During the meeting, EBMT President-Elect Professor Ibrahim Yakoub-Agha from Lille University Hospital in France delivered an insightful lecture titled 'Allo-HCT for Myeloproliferative Neoplasms.' Hematology Frontier invited Professor Yakoub-Agha for an in-depth discussion of key clinical questions, providing valuable guidance for optimizing transplantation strategies in MPNs.Part 1
Oncology Frontier – Hematology Frontier: In current clinical practice, where JAK inhibitors are often used as a bridge to transplantation, how do you determine the optimal timing for transitioning from medical control to allogeneic hematopoietic stem cell transplantation (allo-HCT)? What prognostic indicators guide this decision at your center?
Professor Ibrahim Yakoub-Agha: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm, and treatment decisions must be based on individualized risk assessment. Allogeneic hematopoietic stem cell transplantation remains the only potentially curative approach for some patients, but the indication must be carefully considered. Not every patient is suitable for transplantation, and it is not always necessary to proceed immediately after diagnosis. Instead, patients should be dynamically monitored and their risk of disease progression reassessed over time.The Dynamic International Prognostic Scoring System (DIPSS) remains a classic and clinically valuable tool for this purpose. DIPSS calls for repeated risk evaluation at different time points using parameters such as hemoglobin level, white blood cell count, percentage of bone marrow blasts, presence of constitutional symptoms, and cytogenetic abnormalities. Based on these criteria, patients are stratified into high-risk and low-risk groups.For high-risk patients, allo-HCT is generally recommended, whereas low-risk patients should be monitored regularly and treated with JAK inhibitors or other targeted agents for symptom control.
Clinical decision-making must integrate the patient’s overall status: first, comorbidities that may impact transplant tolerance must be assessed, with age 70 often considered the upper limit for transplant eligibility; second, disease-specific risk stratification must be refined through DIPSS and related tools; and finally, transplant planning must be optimized by selecting the most appropriate donor (HLA compatibility, donor age and health) and conditioning regimen to ensure both safety and efficacy.
Part 2
Oncology Frontier – Hematology Frontier: Recent studies emphasize comprehensive pre-transplant molecular (JAK2, CALR, MPL, and high-risk mutations) and histopathological assessments to predict transplant outcomes. How do you integrate this molecular information into risk stratification, conditioning intensity selection, and post-transplant monitoring?
Professor Ibrahim Yakoub-Agha:Treatment decisions for MF patients should be guided by a multidimensional risk assessment strategy. DIPSS remains the central tool for defining risk, clearly identifying high-risk patients as transplant candidates, while low-risk patients are best managed with active surveillance and symptom control rather than immediate transplantation. The intermediate-risk group presents the greatest challenge, and molecular profiling plays an essential role here.Detection of mutations such as type 1 CALR or high-risk mutations including ASXL1 provides key prognostic insight, signaling a higher likelihood of disease progression. Dynamic monitoring of these molecular markers allows clinicians to identify patients who may benefit from timely transplantation before overt progression occurs, while avoiding overtreatment in those with indolent disease. This decision-making process should follow evidence-based principles, incorporating individual patient factors such as performance status and comorbidities as well as donor availability, to develop a personalized transplant strategy.
Part 3
Oncology Frontier – Hematology Frontier: With advances in molecular monitoring, early immune intervention, and personalized retreatment approaches, which research areas or clinical trials do you expect to have the greatest impact on long-term disease-free survival for MPN patients after allo-HCT over the next three to five years?
Professor Ibrahim Yakoub-Agha: Post-transplant management in MF is complex, with major challenges including graft failure, graft-versus-host disease (GVHD), and relapse. A robust system of dynamic monitoring is essential, with particular focus on molecular markers such as disease-associated mutations and minimal residual disease (MRD) detection. These indicators enable early recognition of relapse or graft rejection.When risk is detected, timely immunomodulatory interventions can be implemented. Adjustments to immunosuppression should aim to balance GVHD prevention with preservation of the graft-versus-leukemia (GVL) effect. Donor lymphocyte infusion (DLI) may be considered to strengthen immune surveillance, and can be combined with other immunomodulatory approaches to maintain durable graft function. The ultimate goal of these strategies is to reduce transplant-related complications, control relapse risk, and maximize the curative potential of allo-HCT.
