Editor’s Note: On October 31, 2025, the International Conference on Cellular Therapy and Biomedical Frontiers, hosted by the Xiong’an Institute for Engineering–Medicine Translational Research of Peking University People’s Hospital and organized by the National Clinical Research Center for Hematologic Diseases / Peking University Institute of Hematology, was grandly held in Xiong’an, Hebei.At the conference, Professor Jae-Ho Yoon from Seoul St. Mary’s Hospital delivered an outstanding presentation titled “Diagnostic and Therapeutic Advances in Korea with Acute Lymphoblastic Leukemia in the Era of Gene Analysis and Targeted Immuno-therapy.”
Following his talk, Oncology Frontier – Hematology Frontier invited Professor Yoon for an in-depth interview to discuss Korea’s latest progress in ALL diagnosis and treatment, clinical experience with targeted immunotherapies, and future research directions, with the aim of providing valuable insights for hematology research and clinical strategy development in China.
Oncology Frontier-Hematology Frontier: Gene analysis and targeted immunotherapy are changing the diagnostic and treatment landscape of acute lymphoblastic leukemia (ALL). Could you share the latest advancements in this field in South Korea, particularly how gene analysis plays a critical role in diagnosis and the development of personalized treatment plans?
Professor Jae-Ho Yoon: Genetic analysis encompasses not only conventional genetic testing but also cytogenetics and molecular genetics, all of which are closely related to acute lymphoblastic leukemia (ALL). The concept of risk stratification originated from acute myeloid leukemia (AML), where the delineation of low-risk, intermediate-risk, and high-risk subgroups is relatively well-established. However, in the field of ALL, risk stratification was first applied to pediatric patients, and it has not yet been fully developed in adult patients.
As experience in pediatric ALL continues to accumulate, we have gradually recognized the necessity for more systematic cytogenetic risk validation in adult ALL. Further studies have revealed that certain genetic abnormalities well-defined in pediatric patients—particularly deletions in genes such as IKZF1, CDKN2, PAX5, and EBF1—are equally significant in adult patients. This additional genetic analysis provides more precise information for prognostic assessment in ALL.
Based on these research findings, we can more clearly identify patient subgroups with poor prognostic risks even after receiving hematopoietic stem cell transplantation or immunotherapy. These molecular-level discoveries offer an important foundation for precise stratification management and individualized treatment decisions in adult ALL patients, making clinical treatment strategies more scientific and accurate.
Oncology Frontier-Hematology Frontier: With the continuous development of targeted immunotherapy, the treatment strategies for ALL are also evolving. What is your perspective on the potential of targeted immunotherapy in improving treatment efficacy and reducing side effects? Which targeted immunotherapy regimens have shown significant results in clinical practice in South Korea?
Professor Jae-Ho Yoon: In the treatment of acute lymphoblastic leukemia (ALL), initial stratification is essential based on Philadelphia chromosome (Ph) status. For Ph-positive ALL, multiple clinical studies conducted at MD Anderson Cancer Center since 2010 have demonstrated that frontline ponatinib combined with conventional or attenuated Hyper-CVAD regimens significantly improves response rates and measurable residual disease (MRD) negativity rates, elevating long-term survival from the previous 40%–50% to approximately 70%. Thus, ponatinib-based regimens have become pivotal in improving survival outcomes for Ph-positive ALL.
Currently, we have entered the era of bispecific T-cell engagers (BiTEs), with blinatumomab—the first approved BiTE agent—playing a central role. In Ph-positive ALL, preliminary data on ponatinib combined with blinatumomab have been published; although follow-up remains short, the results reveal outstanding survival outcomes. However, it is noteworthy that this combination, when used alone, is associated with a higher risk of central nervous system (CNS) relapse.
In Ph-negative ALL, the application of blinatumomab has profoundly transformed the treatment landscape. Beyond its approval for relapsed/refractory disease and MRD-positive cases, it is now progressively incorporated into frontline settings for patients in complete remission with MRD negativity. Studies indicate that blinatumomab-containing regimens achieve high response rates and superior survival outcomes, while offering substantial advantages in reducing chemotherapy intensity and toxicity.
Of particular note, early administration of blinatumomab can render approximately 80% of patients MRD-negative after just one cycle, enabling entry into hematopoietic stem cell transplantation in an optimal state. This facilitates the use of reduced-intensity conditioning regimens, under which patients can still attain favorable long-term survival prognosis even with lower toxicity.
Oncology Frontier-Hematology Frontier: Under the dual driving forces of gene analysis and targeted therapies, South Korea has achieved some breakthroughs in the treatment of acute lymphoblastic leukemia. What do you think the future research focus should be in the treatment of ALL? Specifically, what new technologies or strategies should be emphasized, especially in overcoming drug resistance and improving efficacy?
Professor Jae-Ho Yoon: Currently, the treatment of acute lymphoblastic leukemia (ALL) is actively exploring transplant-free curative strategies. The primary reason this goal was previously unattainable lies in the limited sensitivity and reliability of measurable residual disease (MRD) detection, which hindered accurate interpretation of the clinical significance of MRD-negative results. With the validation of MRD detection methods and the refinement of genomic profiling, transplant-free approaches have now gained a solid feasibility foundation.
For patients without adverse-risk genomic profiles who achieve deep MRD negativity early in treatment, transplant-free regimens can be attempted, supplemented with maintenance therapy such as blinatumomab or conventional/reintensified chemotherapy. In my view, research in this direction represents the most urgent priority at present, necessitating prospective clinical trials to precisely define the patient subgroups most likely to benefit.
On the other hand, for relapsed/refractory ALL patients, it is essential to reevaluate whether allogeneic hematopoietic stem cell transplantation remains the standard of care. With the rapid development of multiple CAR-T cell therapy platforms, clinical practice urgently requires clarification of the optimal application scenarios for CAR-T therapy, immunotherapy maintenance regimens, and allogeneic transplantation in relapsed/refractory cases to maximize therapeutic efficacy.
In summary, precisely identifying the populations suitable for transplant-free treatment and optimizing the best therapeutic pathways for relapsed/refractory cases will constitute the two key directions in future ALL clinical research, enabling more precise, safe, and individualized treatment strategies for patients.
