Editor's Note: Autologous hematopoietic stem cell transplantation (ASCT) is a treatment option for adult acute leukemia in remission. Compared to allogeneic hematopoietic stem cell transplantation (allo-HSCT), ASCT has advantages such as no donor restrictions, absence of graft-versus-host disease (GVHD), and a lower transplant-related mortality rate. At the recent "4th Shanghai Symposium on the Clinical Application of Autologous Hematopoietic Stem Cell Transplantation," Dr. Aiming Pang from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, delivered an insightful presentation on the "Tianjin Model" for ASCT in treating acute leukemia. The highlights of the presentation are summarized here for our readers.

Rapid Growth in Hematopoietic Stem Cell Transplantation in China

In recent years, the number of hematopoietic stem cell transplants in China has grown rapidly. According to the China Hematopoietic Stem Cell Transplantation Registry data, there were 21,533 transplant cases in 2023, with 6,572 (30%) being ASCT and 14,961 (70%) being allo-HSCT. Although the proportion of autologous transplants for acute lymphoblastic leukemia (ALL) remains relatively low, ASCT is still considered an effective treatment for ALL. A study published in Hematology in 2020 reported a 3-year overall survival (OS) rate of 83% for patients with Ph+ ALL treated with ASCT. A 2023 study in British Journal of Haematology suggested that for patients achieving minimal residual disease (MRD)-negative status after chemotherapy, ASCT might be more effective than allo-HSCT. The 2024 Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia recommend considering ASCT for poor prognosis patients without suitable donors (especially those who achieve sustained MRD-negative status) and for good prognosis patients who are MRD-negative following intensive consolidation therapy.

The “Tianjin Model” for Treating Acute Leukemia with ASCT

Since Professor Wenwei Yan performed China’s first autologous transplant at the Institute of Hematology in 1986, nearly 40 years of optimization have led to the development of the “Tianjin Model” for ASCT in acute leukemia.

A multicenter, prospective cohort study led by the Institute of Hematology (ChiCTR2200063863) explored the efficacy and safety of ASCT using either the MCAC (melphalan, cyclophosphamide, cladribine, cytarabine) or TCAC (total body irradiation, cyclophosphamide, cladribine, cytarabine) conditioning regimens. Patients included those with Ph+ ALL achieving s3CMR and Ph- B-ALL patients who achieved MRD-negative status after three cycles of chemotherapy and maintained this status. Patients with a history of central nervous system leukemia, extramedullary infiltration, ETP-ALL, Ph-like ALL, or T-ALL were excluded. As of January 21, 2024, 43 patients were enrolled in the study, with 30 in the MCAC group and 13 in the TCAC group.

The results showed that in the MCAC group, one patient did not achieve neutrophil engraftment (ANC), and two did not achieve platelet engraftment (PLT), while all patients in the TCAC group achieved engraftment. With a median follow-up of 258 days (range: 5–833), there were three deaths, all in the MCAC group: one due to COVID-19 after morphological relapse, one from a cerebral hemorrhage, and one from Legionella pneumonia and encephalitis. Three patients experienced morphological relapse—one in the MCAC group at 90 days post-transplant, and two in the TCAC group at 75 and 390 days post-transplant. Seven patients experienced both molecular and morphological relapse, including three in the MCAC group at 90, 107, and 120 days post-transplant, and four in the TCAC group at 50, 75, 90, and 180 days post-transplant.

Recent Advances in the Field of Acute Leukemia Transplantation

The 2024 Consensus on Autologous Hematopoietic Stem Cell Transplantation for Adult Acute Leukemia, co-authored by Dr. Aimang Pang, was released in July this year. The consensus comprehensively addresses seven aspects of ASCT for adult acute leukemia, including indications, transplant timing, conditioning regimens, stem cell infusion, and post-transplant maintenance therapy. It provides important guidance for improving ASCT outcomes for adult acute leukemia in China.

Achieving MRD-negative remission before transplantation can significantly reduce relapse and improve survival. A meta-analysis involving 21 studies examined the impact of MRD status before allo-HSCT on post-transplant survival, finding that patients with MRD-positive status had a higher relapse rate and poorer prognosis. Achieving MRD-negative status before allo-HSCT was associated with significant survival benefits.

The GRAALL-2014/B study, conducted between December 2015 and December 2020, enrolled 198 Ph-negative adult B-cell precursor (BCP)-ALL patients to evaluate the efficacy of blinatumomab as consolidation therapy. Patients who achieved continuous complete remission (CR) after induction and consolidation 1 received blinatumomab before week 12. Results showed that the blinatumomab group had a significantly higher disease-free survival (DFS) rate (72% vs. 54%) and a lower cumulative relapse rate (20% vs. 41%) over a median of 2.5 years compared to the chemotherapy group.

The INO-VATE study was the first phase III, double-arm trial to compare the efficacy and safety of antibody-drug conjugates (ADC) with standard chemotherapy in Ph+ and Ph- relapsed/refractory B-ALL. The study found that inotuzumab ozogamicin more than doubled the CR/CRi rate compared to standard chemotherapy and had a higher MRD-negative rate. A real-world, single-center study in China, presented at the 2023 EHA meeting, demonstrated that inotuzumab ozogamicin is effective and well-tolerated for induction, maintenance/consolidation, MRD conversion, and relapse/refractory B-ALL treatment in adults.

Ongoing Research and Future Prospects

Several studies led by Professor Erlie Jiang from the Institute of Hematology are underway, including prospective, single-arm clinical trials investigating blinatumomab for MRD relapse in B-ALL patients post-ASCT/allo-HSCT, early use of inotuzumab ozogamicin as maintenance therapy after high-risk B-ALL transplantation, and the use of Nakiolunser injection combined with ASCT for treating MRD-positive adolescent or adult B-ALL in the first CR (CR1). The aim is to continuously improve the efficacy of hematopoietic stem cell transplantation for ALL, ultimately enhancing patient outcomes.

Dr. Aiming Pang

• MD, Chief Physician, Ph.D. Supervisor
• Director of the Stem Cell Transplantation Ward, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
• Member of the Standing Committee, Hematopoietic Stem Cell Transplantation Committee, Chinese Primary Care Foundation
• Standing Committee Member, Hematological Tumor Rehabilitation Committee, Chinese Anti-Cancer Association
• Secretary, Acute Leukemia Autologous Transplantation Collaboration Group, Chinese Hematology Specialty Alliance
• Deputy Director, Hematology Committee, Tianjin Medical and Health Society
• Member, Hemostasis and Thrombosis Committee, Beijing Anti-Cancer Society
• Visiting Scholar at the University of Illinois, Chicago Professor Pang has led numerous scientific projects, including those funded by the National Natural Science Foundation of China and the Tianjin Natural Science Foundation, and has published over 10 papers as the first or corresponding author in international journals such as Science Translational Medicine, Science Immunology, and Blood.