Allografting for Lukemia
白血病同种异体移植
基本信息
- 批准号:8260361
- 负责人:
- 金额:$ 26.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-04-01 至 2013-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAcute Myelocytic LeukemiaAddressAgeAlloantigenAllogenicAllograftingAnimalsAntithymoglobulinAutoimmune DiseasesB-LymphocytesBiologyBone Marrow TransplantationCell TransplantationCell physiologyCellsCellular biologyCessation of lifeChronicChronic DiseaseChronic Lymphocytic LeukemiaClinicClinicalClinical TrialsCyclosporineDevelopmentDiseaseDoseDysmyelopoietic SyndromesElderlyEngraftmentExcisionGraft vs Tumor EffectGraft-Versus-Tumor InductionHematologic NeoplasmsHematopoieticHomologous TransplantationImmuneImmunosuppressionImmunotherapyIndividualInstitutionKiller CellsLymphatic IrradiationMS4A1 geneMaintenanceMalignant NeoplasmsMantle Cell LymphomaMediatingMedicalMonoclonal Antibody CD20Morbidity - disease rateMyeloproliferative diseaseOrgan TransplantationOutcomePatientsPharmaceutical PreparationsPhasePhase III Clinical TrialsPlayPopulationProgram Research Project GrantsReactionRecurrent diseaseRegimenRegulatory T-LymphocyteRelapseResearch PersonnelRiskRoleSiblingsSirolimusSolidT-LymphocyteTestingTissuesToxic effectTranslatingTranslationsTransplantationWhole-Body IrradiationWorkchemotherapychronic graft versus host diseasecytokinedisorder riskeffective therapyefficacy testingfludarabinegraft vs host diseasehigh riskimprovedleukemia/lymphomamycophenolate mofetilneoplastic cellnovelnovel strategiesprophylacticrituximabtreatment strategytumor
项目摘要
Project 1 will serve to translate concepts developed in other Projects to the clinic and build upon our prior
work on developing novel strategies to improve outcomes in patients undergoing allogeneic hematopoietic
cell transplantation (HCT). The concepts developed will likely benefit patients with serious hematological
malignancies but could also provide novel treatment strategies for patients with severe autoimmune
disorders and those undergoing solid organ transplantation. Therefore, the concepts developed are broad
and have significant implications for a number of fields. We will build upon our successful translation of the
studies developed in Project 4 where the novel non-myeloablative regimen of total lymphoid irradiation (TLI)
and anti-thymocyte globulin (ATG) has been explored with marked reduction in acute graft vs host disease
(GVHD) risk with retained graft vs tumor (GVT) responses, The TLI/ATG regimen will be tested as compared
to standard chemotherapy in older (ages 50-75) patients with AML in first CR in a multi-institutional phase III
trial with those patients with HLA matched sibling donors receiving allogeneic HCT and those without treated
with standard chemotherapy (Specific Aim #1). We will attempt to augment the TLI/ATG regimen in two
important ways by utilizing prophylactic administration of cytokine induced killer (CIK) cells developed in
Project 3 in an effort to reduce relapse risk in patients with high risk myeloid malignancies (Specific Aim #2).
A second approach will be to utilize the anti-CD20 monoclonal antibody rituximab in combination with
TLI/ATG in patients with mantle cell lymphoma and chronic lymphocytic leukemia to explore whether this
combined approach will reduce chronic GVHD and disease relapse (Specific Aim #3). Finally we will
translate basic observations in regulatory T cell biology where we have observed that cyclosporine A has a
major impact on Treg function whereas rapamycin and MMF do not. We will test the combination of
RAPA/MMF following myeloablative HCT in patients with high risk malignancies in an effort to reduce GVHD
risk. This Project interacts with all of the other Projects and utilizes all four of the Cores.
项目1将用于将其他项目中开发的概念转化为临床,并建立在我们之前的基础上。
致力于开发新的策略,以改善接受同种异体造血干细胞移植的患者的结局。
细胞移植(HCT)。开发的概念可能会使严重血液病患者受益。
但也可以为严重自身免疫性疾病患者提供新的治疗策略。
疾病和进行实体器官移植的患者。因此,所提出的概念是广泛的
并且对许多领域具有重要意义。我们将在成功翻译的基础上,
在项目4中开发的研究中,采用了新型非清髓性全淋巴照射(TLI)方案,
和抗胸腺细胞球蛋白(ATG)已被探索与急性移植物抗宿主病的显着减少
保留移植物抗肿瘤(GVT)反应的GVHD风险,将测试TLI/ATG方案,
在一项多机构III期研究中,在首次达到CR的老年(50-75岁)AML患者中接受标准化疗
在接受同种异体HCT的HLA匹配同胞供体患者和未接受治疗的患者中进行的试验
标准化疗(具体目标#1)。我们将尝试增加TLI/ATG方案,分为两组,
通过利用预防性施用细胞因子诱导的杀伤(CIK)细胞的重要途径,
项目3旨在降低高风险骨髓恶性肿瘤患者的复发风险(具体目标#2)。
第二种方法将是利用抗CD 20单克隆抗体利妥昔单抗与抗CD 20单抗联合。
TLI/ATG在套细胞淋巴瘤和慢性淋巴细胞白血病患者中的应用,以探讨
联合方法将减少慢性GVHD和疾病复发(具体目标#3)。最后我们将
翻译调节性T细胞生物学中的基本观察结果,我们观察到环孢菌素A具有
主要影响Treg功能,而雷帕霉素和MMF没有。我们将测试
高危恶性肿瘤患者清髓性HCT后RAPA/MMF以减少GVHD
风险该项目与所有其他项目相互作用,并利用所有四个核心。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Robert S Negrin其他文献
Treatment of donors with liposomal alpha-galactosylceramide results in the in vivo expansion of invariant natural killer T cells and reduced incidence of acute graft versus host disease
用脂质体 α-半乳糖神经酰胺治疗供体可导致不变自然杀伤 T 细胞体内扩增,并降低急性移植物抗宿主病的发生率
- DOI:
- 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Toshihito Hirai;Federico Simonetta;Kristina Mass-Bauer;Jeanette Baker;Mustafa Tukoz;Maite Alvarez;Melissa Mavers;Robert S Negrin - 通讯作者:
Robert S Negrin
Robert S Negrin的其他文献
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{{ truncateString('Robert S Negrin', 18)}}的其他基金
Regulatory T cells in allogeneic transplantation
同种异体移植中的调节性T细胞
- 批准号:
9065603 - 财政年份:2012
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T cells in allogeneic transplantation
同种异体移植中的调节性T细胞
- 批准号:
8903997 - 财政年份:2012
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T cells in allogeneic transplantation
同种异体移植中的调节性T细胞
- 批准号:
8534275 - 财政年份:2012
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T cells in allogeneic transplantation
同种异体移植中的调节性T细胞
- 批准号:
8701379 - 财政年份:2012
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T cells in allogeneic transplantation
同种异体移植中的调节性T细胞
- 批准号:
8343992 - 财政年份:2012
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T Cells in Allogeneic Transplantation
同种异体移植中的调节性 T 细胞
- 批准号:
7939868 - 财政年份:2009
- 资助金额:
$ 26.65万 - 项目类别:
Regulatory T Cells in Allogeneic Transplantation
同种异体移植中的调节性 T 细胞
- 批准号:
7855234 - 财政年份:2009
- 资助金额:
$ 26.65万 - 项目类别:
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