On August 22–23, 2025, the 13th Lu Daopei Hematology Conference was held in Beijing, jointly organized by the Beijing Health Promotion Association and the Guangzhou Kapok Oncology and Rare Disease Foundation, and hosted by the Beijing Lu Daopei Hematology Institute. The meeting brought together global leaders in hematology and focused on hematopoietic stem cell transplantation, cellular therapy, and precision management of hematologic malignancies. With more than a thousand participants, the event delivered a high-level academic exchange. During the conference, Professor Xian Zhang from Hebei Yanda Lu Daopei Hospital presented a lecture on “Follow-Up in Acute Lymphoblastic Leukemia Patients Who Did Not Undergo Transplantation After CAR-T Therapy.” Oncology Frontier – Hematology Frontier invited Professor Zhang to further interpret key issues, providing important reference for optimizing clinical management strategies.

PART 1

In ALL patients achieving deep remission after CAR-T therapy, are there clear clinical or biological features that help identify those most suitable for a non-transplant approach? How do you balance relapse risk against transplant-related complications in decision-making?

Professor Xian Zhang: With the growing use of CAR-T therapy in clinical practice, post-treatment strategies for relapsed or refractory acute lymphoblastic leukemia (ALL)—particularly whether to proceed with transplantation after CAR-T remission—have attracted increasing attention.

Since 2012, global clinical experience with CAR-T therapy in ALL has continued to evolve. For CD19 CAR-T, the most widely applied approach worldwide, early reports such as those from Memorial Sloan Kettering Cancer Center showed long-term survival of around 50% regardless of subsequent transplantation. However, our own analysis of 254 patients clearly demonstrated that transplantation after CAR-T–induced remission significantly improves prognosis, while patients who forgo transplantation generally fare poorly, with most succumbing within one to two years.

More recently, as indications expand, even MRD-positive patients have been treated with CAR-T, and some evidence suggests that acceptable survival can be achieved without transplantation. For example, data from Shanghai Children’s Medical Center showed that non-transplanted patients had overall survival rates 10%–20% lower than those who underwent transplantation. At our center, only about 7% of patients did not proceed to transplantation after CAR-T, but their long-term survival exceeded 50%. Analysis revealed that these survivors were typically low-risk patients, such as those with no high-risk features or only low-level MRD, including BCR::ABL1-positive relapses or late relapses with low tumor burden. Maintenance therapy further improved survival in some cases.

By contrast, data for CD7 CAR-T in relapsed/refractory T-ALL and T-LBL remain limited and largely come from Chinese centers within the past four to five years. Our clinical experience indicates that even with deep remission after CD7 CAR-T, transplantation confers significantly better survival. For patients unable to undergo transplantation due to physical condition or financial constraints—particularly those relapsing after a prior transplant—outcomes are poor, with long-term survival of only about 20%. Thus, for patients with relapsed/refractory T-ALL/T-LBL achieving remission with CD7 CAR-T, we recommend proceeding to transplantation as early as possible when feasible, whether first or second transplant.


PART 2

For patients who do not undergo transplantation after CAR-T but achieve long-term survival, systematic follow-up is essential. Could you describe your center’s follow-up protocol, including key milestones, required tests such as MRD monitoring, and duration?

Professor Xian Zhang: Regardless of transplant status, we recommend standardized follow-up at fixed intervals, typically every one to three months, including both bone marrow aspiration and lumbar puncture. In CAR-T recipients, each major follow-up also includes monitoring CAR-T cell persistence and the status of the corresponding target cells.

For CD19 CAR-T patients, in addition to monitoring CAR-T cell levels, we assess CD19-positive B-cell recovery. During CD19 CAR-T therapy, malignant blasts and normal B cells are eliminated simultaneously, resulting in B-cell aplasia (BCA). In long-term non-transplanted survivors, we have observed persistent CD19 CAR-T cells alongside prolonged absence of CD19-positive B cells, which carries favorable clinical implications.

A similar follow-up protocol is applied for CD7 CAR-T patients, although those not proceeding to transplant usually have poorer outcomes. Consequently, such patients may require closer monitoring with more frequent assessments to promptly identify relapse or progression.


PART 3

Based on your data and experience, what are the outcomes for non-transplanted ALL patients after CAR-T therapy? If progression is detected during follow-up, how should subsequent treatments be prioritized? What new insights do follow-up data provide for optimizing future strategies?

Professor Xian Zhang: Among relapsed/refractory B-ALL patients who achieved deep remission with CD19 CAR-T but did not undergo transplantation, long-term survival is around 50%–60%. Importantly, this cohort is highly selected, comprising lower-risk patients such as those with late relapse and low tumor burden, especially BCR::ABL1-positive patients with MRD-level relapse. These individuals tend to show more favorable outcomes.

For such patients, we recommend ongoing MRD monitoring. If MRD begins to rise, we evaluate antigen expression for CD19 and CD22. Depending on the profile, a second CAR-T infusion can be considered, and if remission is achieved again, allogeneic transplantation remains strongly advised.

For T-ALL/T-LBL patients treated with CD7 CAR-T, similar monitoring of CAR-T persistence and CD7 antigen expression is performed. If relapse occurs with re-expression of CD7, retreatment with CD7 CAR-T is an option. If CD7 expression is absent, however, therapeutic choices are limited; chemotherapy or novel targeted agents may be considered, though no highly effective option currently exists.


Expert Profile

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Professor Xian Zhang Hebei Yanda Lu Daopei Hospital

  • Chief Physician, Director, Department of General Hematology and Immunotherapy I
  • PhD in Hematology
  • Member, Hematology Subcommittee, Chinese Medical Doctor Association
  • Member, Hematopoietic Stem Cell Transplantation and Cellular Therapy Group, 5th Hematologic Oncology Committee, Chinese Anti-Cancer Association
  • Member, Cellular Research and Therapy Committee, Chinese Research Hospital Association
  • Member, Human Leukocyte Antigen Expert Panel, Chinese Society of Blood Transfusion
  • Member, Leukemia Immunotherapy Collaborative Group, Chinese Hematology Specialist Alliance
  • Registered Physician, CCPAP Program, China Charity Federation
  • Member, Hematologic Malignancy Subcommittee, Beijing Anti-Cancer Association
  • Member, Red Blood Cell Disorders Committee, Beijing Cancer Prevention and Treatment Society
  • Member, Multidisciplinary Lymphoma Care Committee, Beijing Society of Integrative Medicine
  • Member, Lymphoma Committee, Hebei Hematology Society

Professor Zhang has extensive experience in hematopoietic stem cell transplantation and cellular immunotherapy, with particular expertise in CAR-T therapy and post-transplantation management. He has played a key role in shaping clinical protocols for both B-ALL and T-ALL patients at Lu Daopei Hospital.