The Natural History of Acquired and Inherited Bone Marrow Failure Syndromes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Cohort 3: Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to m...
研究概览
简要总结
Background:
Bone marrow failure diseases are rare. Much is known about the diseases at the time of diagnosis, but long-term data about the effects of the diseases and treatments are lacking. Researchers want to better understand long-term outcomes in people with these diseases.
Objective:
To follow people diagnosed with acquired or inherited bone marrow failure disease and study the long-term effects of the disease and its treatments on organ function.
Eligibility:
People aged 2 years and older who have been diagnosed with acquired or inherited bone marrow failure or Telomere Biology Disorder. First degree family members may also be able to take part in the study.
Design:
Participants will be screened with a medical history, physical exam, and blood tests. They may have a bone marrow biopsy and aspiration. For this, a large needle will be inserted in the hip through a small cut. Marrow will be drawn from the bone. A small piece of bone may be removed.
Participants may also be screened with some of the following:
Cheek swab or hair follicle sample
Skin biopsy
Urine or saliva sample
Evaluation by disease specialists (e.g., lung, liver, heart)
Imaging scan of the chest
Liver ultrasounds
Six-Minute Walk Test
Lung function test
Participants will be put into groups based on their disease. They will have visits every 1 to 3 years. At visits, they may repeat some screening tests. They may fill out yearly surveys about their medicines, transfusions, pregnancy, bleeding, and so on. They may have other specialized procedures, such as imaging scans and ultrasounds.
Participation will last for up to 20 years.
详细描述
Study Description: This study will allow for the long term follow up of patients with acquired and inherited bone marrow failure, both treated and untreated.
Objectives:
Primary Objective
The primary objective is to characterize disease and treatment related long-term outcomes in subjects with inherited or acquired marrow failure.
Secondary Objectives
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •To be eligible to participate in this study, an individual must meet all of the following criteria. Subjects and their family members who undergo screening but ultimately do not meet criteria for cohorts 1-5 will be removed from the study. Subjects may forgo screening and sign directly onto cohorts 1-5 if they meet criteria based on either prior NIH testing or external examinations. Family members will only be asked to be screened for participation onto this study after confirmation of eligibility by an affected participant.
- •Cohorts 1-4
- •Age >=2 years
- •Diagnosis of acquired or inherited bone marrow failure or ineffective hematopoiesis or TBD (see below for cohort 3 specific criteria)
- •Ability and willingness to come to the NIH CC for consultation and testing
- •Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and their willingness to sign a written informed consent document.
- •For cohort 3 - TBD:
- •Presence of a pathogenic, likely pathogenic, or known family mutation in a telomere maintenance gene
- •If mutation negative or VUS, telomere length <10th percentile in lymphocytes with at least two clinical features: 1) cytopenia (Hb <10g/dL or ANC <1.5x10^9 or platelets <100), 2) documented liver fibrosis by histology OR abnormal liver US / fibro scan consistent with fatty liver or fibrosis), 3) documented pulmonary fibrosis by histology / radiology OR PFTs showing FEV1 <80% or DLCO <60%, 4) family history of: marrow failure, myeloid malignancy, liver fibrosis or lung fibrosis.
- •Age >= 2 years
- •First degree family member with a known or suspected inherited bone marrow failure syndrome from a patient enrolled on this or another NIH protocol as determined by a PI or AI
- •Ability and willingness to safely provide blood, buccal swab, or fibroblasts for testing as stated by subject
- •Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and the willingness to sign a written informed consent document.
排除标准
- 未提供
研究组 & 干预措施
Cohort 1
Severe Aplastic Anemia(SAA): Age 2 and older; Previous diagnosis of bone marrow failure
Cohort 2
Other Marrow Failure: Age 2 and older; Previous diagnosis of bone marrow failure;
Cohort 5
Family Screening: Age 2 and older; First degree family member with a known or suspected inherited bone marrow failure syndrome
Cohort 3
Telomere Biology Disorders(TBD): Age 2 and older; Previous diagnosis of bone marrow failure
Cohort 4
Inherited Bone Marrow Failure(IBMF)Syndromes: Age 2 and older; Previous diagnosis of bone marrow failure
结局指标
主要结局
Cohort 3: Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to m...
时间窗: 20 years
Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to morbidity and mortality.
Cohort 2: Rate of progression requiring therapeutic intervention
时间窗: 20 years
Rate of progression (cytopenias or clonal evolution) requiring therapeutic intervention.
Cohort 1: Rate of relapse and clonal evolution in previously treated patients
时间窗: 20 years
Rate of relapse and clonal evolution in previously treated patients
Cohort 4: Rate of progression to transfusion dependent marrow failure, marrow failure requiring therapeutic intervention (such as medical therapy or HSCT) or the progression to hematological malignancy
时间窗: 20 years
Rate of progression to transfusion dependent marrow failure, marrow failure requiring therapeutic intervention (such as medical therapy or HSCT) or the progression to hematological malignancy.
次要结局
未报告次要终点