Graft Characterization and Monitoring of Immune Hematopoietic Reconstitution

免疫造血重建的移植物表征和监测

• 批准号: 8435574
• 负责人: MIGUEL-ANGEL PERALES
• 金额: $ 32.15万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8435574
• 关键词: Adoptive Immunotherapy; Adult; Age; Alleles; Alloantigen; Allogenic; Allografting; Ambulatory Care Facilities; Androgens; Antibody Formation; Antigens; B-Lymphocytes; Biological; Biological Assay; Blood Cells; Bone Marrow; CD4 Positive T Lymphocytes; Cause of Death; Cell Therapy; Cells; Chimerism; Clinical; Clinical Research; Clinical Trials; Core Facility; Data; Dendritic Cells; Detection of Minimal Residual Disease; Development; Elements; Engraftment; Failure; Flow Cytometry; Funding; Genetic; Gonadal Steroid Hormones; Graft Rejection; Grant; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Human; Immune; Immune system; Immunologic Monitoring; Infection; Infusion procedures; Inpatients; Instruction; Intervention; Kinetics; Laboratories; Malignant - descriptor; Marrow; Memorial Sloan-Kettering Cancer Center; Methods; Mitogens; Molecular; Monitor; Morbidity - disease rate; Mycoses; Natural Killer Cells; Non-Neoplastic Hematologic and Lymphocytic Disorder; Opportunistic Infections; Outcome; Parasitic infection; Patients; Phenotype; Population; Prevention; Recovery; Recovery of Function; Recurrent disease; Regimen; Relapse; Research; Research Project Grants; Residual Neoplasm; Residual state; Resistance; Resolution; Risk; Second Primary Cancers; Series; Source; Specimen; Stem cells; T cell response; T-Cell Depletion; T-Cell Receptor-Rearrangement Excision DNA Circles; T-Lymphocyte; Testing; Toxic effect; Transplantation; Umbilical Cord Blood; Virus Diseases; base; chemotherapy; conditioning; cytokine; deep sequencing; design; experience; graft vs host disease; improved; in vivo; leukemia; monocyte; mortality; peripheral blood; prevent; reconstitution; repository

PROJECT SUMIVIARY (See instructions): Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established curative approach for a variety of malignant and nonmalignant hematologic disorders. Disease relapse, graft versus host disease (GVHD), infection, and regimen related toxicity remain the primary causes of transplant failure. The tempo and quality of hematopoietic engraftment and immune reconstitution significantly influence post-HSCT morbidity and mortality. Adult recipients of an allo-HSCT experience deficiencies in their B and T cell reconstitution, which can persist for over a year, and are associated with an Increased risk of infection, relapse, and secondary malignancies. Delayed reconstitution of CD4 T cells, associated with advanced patient age, HLA disparity, and method of prevention of GVHD and graft rejection, correlates with an increased risk of fatal opportunistic infections. Despite the increased use of molecular typing of HLA alleles for more stringent matching of patient and unrelated donors, and intensified regimens to prevent and treat invasive viral, fungal, and parasitic infections, opportunistic infections represent the primary cause of death in most unrelated transplant series, regardless of the stem cell source (bone marrow, peripheral blood, or cord blood), and irrespective ofthe use of T cell depletion. The clinical trials and research projects outlined in this grant are designed to test transplant approaches, biologicals and cell therapies to accelerate full functional recovery of the hematopoietic and immune systems and provide immune T-cells to eradicate viral infections and enhance resistance to leukemia in recipients of allo-HSCT. The purpose of Core A is to define hematopoietic cell grafts and adoptively transferred T-cells and their function prior to and following HSCT. Core A will characterize allografts and monitor the effects of stem cell source, donor type, use of T cell depletion, immunomodulatory agents, such as KGF or androgen blockade, and/ or adoptive immunotherapy, as well as development of GVHD on the kinetics and quality of immune reconstitution, donor chimerism, and minimal residual disease. Core A will also centralize specimen procurement and provide a centralized storage repository.

项目摘要（参见说明）：同种异体造血干细胞移植（allo-HSCT）是治疗多种恶性和非恶性血液疾病的既定治疗方法。疾病复发、移植物抗宿主病（GVHD）、感染和治疗相关毒性仍然是移植失败的主要原因。造血移植和免疫重建的速度和质量显着影响 HSCT 后的发病率和死亡率。接受同种异体造血干细胞移植的成年受者会出现 B 细胞和 T 细胞重建缺陷，这种缺陷可能会持续一年以上，并且与感染、复发和继发性恶性肿瘤的风险增加有关。 CD4 T 细胞的延迟重建与高龄患者、HLA 差异以及预防 GVHD 和移植物排斥的方法相关，与致命机会性感染风险增加相关。尽管越来越多地使用 HLA 等位基因的分子分型来更严格地匹配患者和无关捐赠者，并强化治疗方案来预防和治疗侵入性病毒、真菌和寄生虫感染，但机会性感染仍然是大多数无关移植系列中死亡的主要原因，无论干细胞来源如何（骨髓、外周血或脐带血），也无论是否使用 T 细胞去除。这笔赠款中概述的临床试验和研究项目旨在测试移植方法、生物制剂和细胞疗法，以加速造血和免疫系统的全面功能恢复，并提供免疫 T 细胞来根除病毒感染并增强接受者对白血病的抵抗力。同种异体造血干细胞移植。核心 A 的目的是定义造血细胞移植物和过继转移的 T 细胞及其在 HSCT 之前和之后的功能。核心 A 将表征同种异体移植物并监测干细胞来源、供体类型、T 细胞耗竭的使用、免疫调节剂（例如 KGF 或雄激素阻断和/或过继性免疫疗法）的影响，以及 GVHD 的发展对动力学和质量的影响免疫重建、供体嵌合和微小残留病。核心A还将集中标本采购并提供集中存储库。