Natural History of Acquired and Inherited Bone Marrow Failure Syndromes

NCT05012111 | Recruiting

• 2 other identifiers: 10000387000387-H
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Severe Aplastic Anemia; Telomere Biology Disorders; Inherited Bone Marrow Failure Syndromes

Keywords

Aplastic Anemia; Telomere; Natural History

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  20 years

• 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...

  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.

  20 years

• Cohort 1: Rate of relapse and clonal evolution in previously treated patients

  Rate of relapse and clonal evolution in previously treated patients

  20 years

• Cohort 2: Rate of progression requiring therapeutic intervention

  Rate of progression (cytopenias or clonal evolution) requiring therapeutic intervention.

  20 years

Study Arms (5)

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 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

Cohort 5

Family Screening: Age 2 and older; First degree family member with a known or suspected inherited bone marrow failure syndrome

Eligibility Criteria

• Age: 2 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with Severe Aplastic Anemia, other acquired marrow failure syndromes, and inherited marrow failure syndromes. Family members of subjects with either suspected or confirmed inherited bone marrow failure.

You may qualify if:

• 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.
• Cohort 5
• 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.

You may not qualify if:

• None

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Emma M Groarke, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania R Machado

CONTACT

(301) 661-1505; tania.machado@nih.gov

Emma M Groarke, M.D.

CONTACT

(301) 496-5093; emma.groarke@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 19, 2021
• Study Start: October 25, 2021
• Primary Completion (Estimated): February 4, 2041
• Study Completion (Estimated): February 4, 2041
• Last Updated: May 6, 2026

Record last verified: 2026-05-04

Locations

US (1)