Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization
研究概览
简要总结
Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2 and DNMT3a. Donor lymphocyte infusion (DLI) is an option to reduce relapse after allo-PBSCT for very high-risk disease without effective targeted therapy. In this study, the investigators aimed to compare the safety and efficacy of prophylactic DLI with G-CSF-primed peripheral blood progenitors for prevention of relapse after allo-PBSCT in patients with very high-risk leukemia/lymphoma.
详细描述
Conventional DLI has invariably been associated with high rates of severe graft-versus-host disease (GVHD) and GVHD-related non-relapse mortality (NRM). Thus, in our previous studies, the DLI procedure has been modified to use G-CSF-mobilized peripheral blood stem cells (PBSCs) instead of steady-state lymphocytes. G-CSF mobilization results in the modulation of the polarization potential of T cells from Th1 to Th2. In addition, T-cell hyporesponsiveness is induced via the proliferation of dendritic cell 2 and monocytes and the down-regulation of CD28/B7. Furthermore, G-CSF augments NK-T-cell-dependent CD8+ cytotoxicity. These data constructed the rationale for the use of G-CSF-primed peripheral blood DLI to reduce DLI-associated GVHD and enhance the GVT effect of DLI. To date, there is no effective target therapy for acute leukemia with gene mutations such as DNMT3A, TET2 and TP53 and their response to chemotherapy and survival even after allogenic stem cell transplantation remains poor. Hypomethylating agents were reported to reverse the repression of HLA molecules and cancer testis antigens on leukemia cells, rendering them more sensitive to anti-leukemic activity mediated by DLI. The use of low-dose decitabine after allogenic stem cell transplantation was safe for early hematopoietic reconstitution. Therefore, decitabine was planned to be given prior to prophylactic DLI in the current study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •disease in the non-remission (NR) state prior to transplantation, including primary induction failure, relapse untreated or refractory to reinduction chemotherapy.
- •achieving CR1 with ≥3 cycles of induction of chemotherapy.
- •carrying TP53, DNMT3a, TET2 or FLT3-ITD gene mutation.
排除标准
- •early relapse, either molecular relapse or hematological relapse.
- •primary or secondary graft failure.
- •concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart, renal, respiratory or hepatic failure…).
结局指标
主要结局
Cumulative incidence of non-relapse mortality (NRM) at 1 year after randomization
时间窗: 1 year
NRM was defined as death from any cause without relapse. Cumulative incidence of NRM was analyzed in a competing risk framework using Gray's method.
Cumulative incidence of relapse at 1 year after randomization
时间窗: 1 year
Relapse was defined as hematologic recurrence of malignancies after transplantation. Cumulative incidence of relapse was analyzed in a competing risk framework using Gray's method.
次要结局
- Relapse-free survival (RFS) at 1 year after randomization(1 year)
- Cumulative incidence of acute GVHD at 100 days after randomization(100 days)
- Cumulative incidence of chronic GVHD at 1 year after randomization(1 year)
研究者
Daihong Liu
Head of Hematology
Chinese PLA General Hospital