Blinatumomab Sequential Donor Lymphocyte Infusion in Acute B Lymphocytic Leukemia Observation of Therapeutic Effect in Patients With Recurrence After Allogeneic Hematopoietic Stem Cell Transplantation
Phase: PHASE4
Conditions: Acute B-cell Lymphoblastic Leukemia
Sponsor: Suping ZHANG

Study v 1.1 Date: 15 November 2023 
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Name of project：Efficacy of Blinatumomab  sequential donor 
lymphocyte infusion in patients with relapsed B-cell acute lymphoblastic 
leukemia after allogeneic hematopoietic stem cell transplantation 
Institution Name: The First Affiliated Hospital of Zhengzhou University 
Study start date: September 2023 
Study deadline: December 2026 
 
 
 
 
 
 
 
 
 

Study v 1.1 Date: 15 November 2023 
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Efficacy of Blinatumomab  sequential donor lymphocyte infusion in 
patients with relapsed B-cell acute lymphoblastic leukemia after 
allogeneic hematopoietic stem cell transplantation 
 
Subject name: Efficacy of Blinatumomab  sequential donor lymphocyte infusion in 
patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic 
hematopoietic stem cell transplantation 
 
Purpose of the study 
Objective To observe and analyze the efficacy and side effects of Blinatumomab 
followed by donor lymphocyte infusion in patients with relapsed acute B lymphoblastic 
leukemia after allogeneic hematopoietic stem cell transplantation in our hospital. This 
study explores the treatment of patients with relapsed B-cell acute lymphoblastic 
leukemia after allogeneic hematopoietic stem cell transplantation. 
 
Background of Research 
Acute lymphoblastic leukemia (ALL) is a malignant blood disease. The traditional 
treatment mainly includes chemotherapy and hematopoietic stem cell transplantation. 
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and 
even the only means to cure ALL and other malignant blood diseases. However, acute 
lymphoblastic leukemia still has a high recurrence rate after allo-HSCT, and the 
prognosis of patients with relapse after transplantation is extremely poor, with an 
average survival time of about 5.5 months. There is no uniform treatment for patients 
with relapse after allogeneic hematopoietic stem cell transplantation. Donor 
lymphocyte infusion (DLI) is the main salvage treatment for relapse after 
transplantation, but in the treatment of relapse after allo⁃HSCT for ALL patients, the 
efficacy is often poor, and less than 20% of patients can achieve remission. Relapse 
after allogeneic hematopoietic stem cell transplantation in ALL is still an urgent clinical 
problem to be solved. 
In recent years, chimeric antigen receptor T cell (CAR⁃T) therapy targeting CD19 can 
achieve hematological complete response (CR) in 60% to 90% of patients with 
refractory and relapsed acute B⁃ lymphoblastic leukemia (B⁃ALL), creating an 
opportunity for the long-term survival of such patients. However, the cost of CD19+ 
CAR⁃T therapy currently on the market in China is extremely expensive, and the vast 
majority of patients cannot receive this treatment. Blinatumomab is the first CD19-
positive and CD3-positive targeted immunotherapy drug approved by the FDA in the 
United States and has also been approved for relapsed or refractory B-ALL in adults 
and children in China. By linking CD3 on T cell receptor complexes with CD19 
expressed on B cell line-derived cells, Blinatumomab aggregates T cells with target 
cells by forming cytolytic synapses, thus activating endogenous T cells and enabling 
them to solubilize CD19+ cells for tumor cell killing. In an open-label single-arm phase 

Study v 1.1 Date: 15 November 2023 
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II study in adults with B-ALL, Blinatumomab achieved a 43% complete response rate 
(CR) or peripheral blood count (CRh) partial blood recovery rate (CR) over 2 treatment 
cycles, among 64 patients who relapsed after allo-HSCT, 45% of patients achieved 
CR/CRh in the first two treatment cycles, and 22 patients had minimal residual disease 
(MRD) response (including 19 complete MRD response). After 1 year and 3 years of 
follow-up, the median relapse-free survival of patients who achieved CR/CRh in the 
first 2 cycles was 7.4 months, and the median overall survival was 8.5 months. Overall 
survival (Kaplan-Meier estimates) was 36% at 1 year and 18% at 3 years. Grade 3 and 
4 adverse events were reported in 20 patients (31%) and 28 patients (44%), respectively, 
including grade 3 and 4 neurological events in 8 and 2 patients, respectively, and grade 
3 cytokine release syndrome in 2 patients. Fatal adverse events occurred in eight 
patients, including five due to infection. Seven patients developed grade 3 GVHD 
during the study, none of which resulted in drug withdrawal or hospitalization. The 
results confirm that Blinatumomab is an effective salvage therapy in refractory B-cell 
acute lymphoblastic leukemia in this patient population. 
In this study, patients with relapsed acute B lymphoblastic leukemia after allogeneic 
hematopoietic stem cell transplantation (allo-HSCT) were treated with blinatumomab 
followed by DLI. The overall survival, disease-free survival, complications, adverse 
reactions, and other indicators of these patients were observed. To investigate the 
treatment of relapsed B-cell acute lymphoblastic leukemia after allogeneic 
hematopoietic stem cell transplantation. 
 
Criteria for inclusion of subjects 
Patients with acute B lymphoblastic leukemia who relapsed after allogeneic 
hematopoietic stem cell transplantation in our hospital and received Blinatumomab 
sequential DLI after relapse. Patients with acute B lymphoblastic leukemia who 
relapsed after allogeneic hematopoietic stem cell transplantation in our hospital from 
September 2023, to December 2026, were enrolled. After relapse, patients were treated 
with Blinatumomab sequential donor lymphocyte infusion (DLI). 
1. Age ≤65 years old 
2. Stable vital signs 
3. No severe infection 
4. There was no degree II-IV graft-versus-host disease 
5. No organ failure 
 
Criteria of exclusion 
1. Age > 65 years old 
2. Unstable vital signs 
3. Complicated with severe infection 
4. Combined with degree Ⅱ-Ⅳ graft-versus-host disease 
5. Heart, liver, kidney and other organ failure 
6. Complicated with central nervous system leukemia 
7. Allergies to medications in the treatment regimen 
 

Study v 1.1 Date: 15 November 2023 
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Treatment plan 
B-ALL patients received regular follow-up after allogeneic hematopoietic stem cell 
transplantation. In case of recurrence, they were treated with Blinatumomab followed 
by DLI, and the second course of treatment was carried out 1-2 months after DLI. 
In MRD-positive patients, Blinatumomab  28μg×5-15 days were given, followed by 
DLI therapy (infusion of MNC was about 5×10^7/kg~1×10^8/kg). 
Patients with hematologic recurrence were given Blinatumomab  9μg D1-4,11.66μg d5-
7, 28μg d8 (for a total of 8 to 21 days), followed by DLI therapy (infusion of MNC was 
about 5×10^7/kg~1×10^8/kg). 
The use time of the barstool is determined according to the patient's tolerance, economic 
situation, and other comprehensive factors. 
Main observations and statistical indicators 
Overall survival, disease-free survival, cytokine release syndrome (CRS) incidence, 
acute/chronic graft-versus-host disease (GVHD) incidence, infection incidence, 
hematological adverse reactions, etc. 
 
Case data collection 
The electronic medical record system of our hospital was used to review the data of B-
ALL patients who relapsed after allogeneic hematopoietic stem cell therapy and 
received Blinatumomab followed by DLI after relapse. Pay attention to protect the 
privacy of patients and ensure that the personal information of patients' case data is not 
disclosed. 
 
Statistical analysis 
SPSS26.0 software was used for statistical analysis. The χ2 test and Mann-Whitney U 
test were used to compare qualitative and quantitative data between groups, respectively. 
The survival rate and survival analysis were estimated by the Kaplan-Meier method, 
and the Log-rank test was used for comparison between the two groups. P<0.05 was 
considered statistically significant. 
 
 
Project leader: Zhilei Bian Principal investigator: Zhilei Bian 
Address: Department of Hematology, Hematopoietic Stem Cell Transplantation Center, 
The First Affiliated Hospital of Zhengzhou University (1) 
Efficacy of Blinatumomab  sequential donor lymphocyte infusion in patients with 
relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell 
transplantation