异基因造血干细胞移植是恶性血液病有效乃至唯一的根治手段，申请人团队建立的原创单倍型移植体系解决了供者来源问题，但造血干细胞植入功能不良仍是影响移植预后的严重并发症。我们前期通过临床队列研究发现：①植入功能不良患者骨髓微环境受损、造血干细胞数量减少；②供者特异性HLA抗体（DSA）阳性与植入功能不良发生密切相关，但植入功能不良的机制尚待阐确。因此，本课题拟充分利用临床研究平台、体外实验及动物模型，从造血干细胞、骨髓微环境和免疫角度，阐明骨髓微环境改变与造血干细胞减少在植入功能不良发生中的因果关系、DSA导致植入功能不良以及现有干预策略的细胞/分子学基础，从而阐明植入功能不良及其干预机制，改善植入功能不良患者预后，进一步完善我国原创的单倍型移植体系。本课题的顺利实施，对于优化植入功能不良临床防治策略和制定临床新路径，以及巩固我国原创的单倍型移植体系的国际领先性具有重大意义。

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is an effective and sometimes the only curative therapy for patients with hematologic malignancies. The progress in unmanipulated haploidentical/mismatch HSCT, partially due to our established system, makes almost everyone has donor. However, the poor graft function (PGF) of CD34+ hematopoietic stem cells (HSC) remains a critical complication of allo-HSCT, which negatively affects the clinical outcomes. Our previous clinical cohort studies demonstrated that the HSC decreased in PGF patients while the bone marrow microenvironment was impaired, and the preliminary data also showed the positive correlation of donor specific antibody (DSA) with PGF. Nonetheless, the mechanism of PGF remains unclear. Based on clinical platform, in vitro experiments and animal model, this study attempts to clarify the causal relationship between the bone marrow microenvironment change and the decrease in HSC, the cellular and molecular mechanism of DSA and intervention methods for PGF, from the perspective of HSC, bone marrow microenvironment and immune-factors. The successful implementation of this project will provide the basis to optimize the strategies for the prophylaxis and treatment of PGF, and it may improve the transplantation outcomes of PGF patients, thus making our haploidentical transplantation modality more mature.