-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1445 Significant Long-Term Benefits of CAR T-Cell Therapy Followed By a Second Allo-HSCT for Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (B-ALL) Patients Who Relapsed after an Initial Transplant

Program: Oral and Poster Abstracts
Session: 704. Immunotherapies: Poster I
Hematology Disease Topics & Pathways:
CRS, Adult, Leukemia, ALL, Biological, neurotoxicity, Diseases, CAR-Ts, Therapies, Adverse Events, Pediatric, immunotherapy, Study Population, Lymphoid Malignancies, Clinically relevant, transplantation
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Jianping Zhang1*, Junfang Yang2,3*, Xian Zhang, MD2,3, Jingjing Li2,3*, Xingyu Cao1*, Yanli Zhao1*, Zhijie Wei1*, Deyan Liu1*, Min Xiong3*, Yue Lu1*, Jiarui Zhou3*, Ruijuan Sun1* and Peihua Lu, MD2,3

1Bone Marrow Transplant Department, Hebei Yanda Lu Daopei Hospital, Langfang, China
2Beijing Lu Daopei Institute of Hematology, Beijing, China
3Hebei Yanda Lu Daopei Hospital, Langfang, China


Current available treatments are limited once patients with B-ALL relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT). While chimeric antigen receptor (CAR) T-cell therapy offers a chance of remission, long-term outcomes for these patients remain poor. The benefit of bridging into a second transplant after CAR T-cell therapy remains inconclusive and available data are limited. Here, we report the long-term outcomes of 23 B-ALL patients who chose to undergo a second allo-HSCT after achieving complete remission (CR) from CAR T-cell therapy.


From April 2017 to April 2020, 23 R/R B-ALL patients (median age of 20 years, ranging from 3 to 58 years) who relapsed after first allo-HSCT received CAR T-cell therapy. The data were aggregated from seven different clinical trials (www.clinicaltrials.gov NCT03173417, NCT02546739 NCT03825718, NCT03825731, NCT03952923, NCT04100187 and www.chictr.org.cn ChiCTR1800016541). Patients’ first transplant sources were HLA-identical sibling (n=5), matched-unrelated donor (MUD) (n=1), and haploidentical donors (haplo) (n=17). Eight of the 23 patients had disease relapse within 6 months following the first transplant. The median time from first transplant to CAR T-cell infusion was 261days (range: 117~2181 days). Before CAR T-cell infusion, patients’ median bone marrow (BM) blasts by morphology were about 72.5% (1.5%-94.5%) including 12 patients with BM blasts >70% (5 with BM blasts >90%). Three of the 23 patients (13%) had received at least one prior donor lymphocyte infusion. No patients had active graft-versus-host disease (GVHD) prior to CAR T-cell therapy. Second generation CAR T-cells were generated by using purified T-cells from transplant donors (n=15) or patients (n=8). Twenty-two patients received T-cells modified with CD19-targeting CAR T-cells containing either a 4-1BB (n=18) or a CD28 co-stimulatory domain (n=4), and one patient received CD19-CD22 dual specificity CAR T-cells. All patients received a conditioning regimen of IV fludarabine (30mg/m2/d) and cyclophosphamide (250mg/m2/d) for 3 days followed by a single CAR T-cell infusion with a median dose of 3×105 cells/kg (1×105-6×105 cells/kg) in 21 patients. Two patients received a second CAR T-cell infusion in 2-3 months (1/3×105 cells/kg dose). Post CAR-T therapy, all patients bridged into a consolidation second transplantation with conventional myeloablative pre-transplantation conditioning regimens including 15 patients who received total body irradiation-based and 7 patients that received a busulfan-based conditioning regimen. Cyclosporin A, short-term methotrexate, and mycophenolate mofetil were used for GVHD prophylaxis.


Patients’ characteristics are shown in Table 1. On Day 30 post CAR-T-cell infusion, 23/23 (100%) patients achieved minimal residual disease (MRD)-negative CR. A total of 16/23 (69.6%) patients developed cytokine release syndrome (CRS) of which 14/23 (60.9%) had Grade I-II and 2/23 (8.7%) had Grade III CRS. Two patients had Grade III neurotoxicity. All patients with MRD-negative status subsequently bridged into a second transplant (2 from MUD and 21 from haplo donors) with a median interval time of 67 days (39- 329 days) from CAR T-cell therapy to a second transplant. At a median follow-up time of 258 days (84-978 days), no patients relapsed, which was encouraging. Five of 23 patients (21.7%) died from transplant-related mortality (TRM) at a median time of 295 days (103-372 days) (1 from GVHD and 4 from infection). The 1-year overall survival (OS) was 68.0% and 2-year OS was 54.4% (Fig.1). While there was a trend towards a more efficacious OS for patients whose CAR T-cells were derived from donors rather than from patients themselves but the number are too small to reach statistical significance (1-year OS 83.9% vs. 64.3%, 2-year OS 83.9% vs. 42.9%, P=0.739. Fig.2). After the 2nd transplant, four patients developed GVHD.


Our study demonstrates that even for R/R B-ALL patients who have relapsed following a first allo-HSCT , an MRD-negative CR status can still be achieved through CAR T-cell cell therapy without increasing CRS or neurotoxicity, making consolidation second allo-HSCT feasible for these patients. CAR T-cell therapy combined with a consolidation second HSCT are effective for these heavily pre-treated patients with an encouraging prospect for long-term survival.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH