The 2026 European Hematology Association (EHA) Congress, held from June 11–14 in Stockholm, Sweden, brought together leading experts from around the world to showcase the latest advances in basic, translational, and clinical hematology.At this year’s meeting, the team led by Professor Jiarui Zhou and Dr. Jingyu Wang from Lu Daopei Hospital presented a study focusing on adult TCF3::PBX1-positive acute lymphoblastic leukemia (ALL), a challenging high-risk subtype associated with poor long-term outcomes. The investigators explored the clinical value of CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, importantly, evaluated how the number of prior CAR-T infusions may influence transplant outcomes. Their findings provide valuable evidence for optimizing treatment strategies in patients with relapsed or refractory disease.
Study Overview
Title: Efficacy of CAR-T Bridging to Allo-HSCT in Adult TCF3::PBX1+ ALL: Impact of Infusion Frequency
First Author: Dr. Jingyu Wang Corresponding Author: Professor Jiarui Zhou
Background
The TCF3::PBX1 (E2A-PBX1) fusion gene is a recurrent cytogenetic abnormality in precursor B-cell acute lymphoblastic leukemia (B-ALL), occurring in approximately 5–6% of pediatric cases and about 3% of adult cases.
This subtype is generally regarded as a high-risk form of ALL. Although patients often achieve high rates of complete remission (CR) with initial chemotherapy, relapse remains common and long-term outcomes are poor. Allogeneic hematopoietic stem cell transplantation has historically been one of the few approaches capable of improving long-term survival.
CAR-T cell therapy has revolutionized the treatment of relapsed or refractory B-ALL, producing high remission rates. However, relapse after CAR-T remains a major challenge, with reported cumulative relapse rates ranging from 20% to 70%. As a result, many patients undergo allo-HSCT as consolidation therapy following CAR-T-induced remission. Nevertheless, transplant-related complications can offset some of the benefits associated with reduced relapse risk, and the necessity of routine transplantation after CAR-T remains an area of ongoing debate.
Methods
This retrospective study analyzed 49 adult patients with TCF3::PBX1-positive ALL who underwent allogeneic HSCT at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital between November 2013 and January 2025.
Patients were divided according to whether they had received CAR-T therapy before transplantation:
- CAR-T group: 29 patients
- Non–CAR-T group: 20 patients
The CAR-T cohort was further subdivided into:
- Single CAR-T infusion subgroup: 23 patients
- Multiple CAR-T infusion subgroup: 6 patients (≥2 infusions)
Baseline characteristics, engraftment outcomes, graft-versus-host disease (GVHD), relapse rates, and overall survival (OS) were compared between groups.
Results
Patients in the CAR-T cohort were predominantly those with relapsed or refractory disease. Compared with the non–CAR-T group, a significantly larger proportion of patients had undergone transplantation in second or third complete remission (CR2/CR3) (86.2% vs. 10.0%, P<0.001).
The incidence of acute GVHD was similar between the two groups:
- CAR-T group: 44.8%
- Non–CAR-T group: 50.0%
- P=0.728
A striking difference emerged when outcomes were analyzed according to CAR-T infusion frequency.
Patients who received a single CAR-T infusion before transplantation achieved a 1-year overall survival rate of 68.5%, indicating favorable post-transplant outcomes.
In contrast, outcomes were extremely poor among patients who had undergone multiple CAR-T infusions. All patients in this subgroup died within one year after transplantation, resulting in:
- 1-year OS: 0%
- Median OS: 4.2 months
Among deaths occurring in the CAR-T cohort, the leading causes were:
- Infection (42.9%)
- Disease relapse (21.4%)
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Conclusions
The study suggests that CAR-T therapy followed by allo-HSCT represents an effective salvage strategy for patients with relapsed or refractory TCF3::PBX1-positive ALL.
Key findings include:
- Single CAR-T infusion followed by transplantation was associated with encouraging survival outcomes and may reduce the risk of chronic GVHD.
- A second transplantation was not identified as an independent adverse prognostic factor.
- Multiple CAR-T infusions prior to transplantation were strongly associated with exceptionally high transplant-related mortality.
These findings raise concerns that repeated CAR-T exposure may lead to profound immune dysfunction or disruption of the hematopoietic microenvironment. Therefore, for patients being considered for allo-HSCT after CAR-T therapy, clinicians should carefully evaluate prior CAR-T treatment history and immune status before proceeding with transplantation.
About the Investigators
Professor Jiarui Zhou
Director, Department of Hematopoietic Stem Cell Transplantation, Lu Daopei Hospital
Professor Zhou graduated from Capital Medical University and joined the Lu Daopei Group in 2002. She currently serves as Director of the Hematopoietic Stem Cell Transplantation Departments at both Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital.
Since entering the field of hematology in 2000, she has accumulated extensive expertise in the diagnosis and treatment of hematologic diseases. As one of the earliest physicians trained within the institution to perform stem cell transplantation, she has directly participated in more than a thousand transplant procedures and was among the pioneers of haploidentical transplantation in China.
Professor Zhou has played a leading role in developing post-transplant follow-up programs and is recognized for designing individualized conditioning and treatment strategies that improve outcomes while reducing transplant-related complications and economic burden. She is also regarded as a pioneer of CAR-T–bridged transplantation, with one of the earliest recipients of this approach now surviving more than 11 years post-transplant with excellent quality of life.
Her experience spans patients ranging from infants to elderly adults, including complex salvage transplantation cases and repeat transplant recipients with exceptionally long-term survival.
Dr. Jingyu Wang
Attending Physician, Department of Hematopoietic Stem Cell Transplantation, Lu Daopei Hospital
Dr. Wang graduated from the University of South China School of Medicine and has worked in the Department of Hematopoietic Stem Cell Transplantation at Lu Daopei Hospital since 2015.
Over more than a decade in the field, she has gained extensive experience in stem cell transplantation for a wide range of hematologic disorders, including leukemia, aplastic anemia, myelodysplastic syndromes, and hemophagocytic lymphohistiocytosis.
Working under the mentorship of Professor Zhou, Dr. Wang has participated in more than 300 transplant procedures for relapsed or refractory diseases. She has developed particular expertise in the diagnosis and management of post-transplant complications, including acute and chronic GVHD, infections, hemorrhagic cystitis, viral reactivation, and disease relapse.
