Retrospective Study of Patients With Severe Aplastic Anemia Who Developed High Risk Clonal Evolution With Chromosome 7 Abnormalities After Immunosuppressive Therapy

Background:

Severe aplastic anemia (SAA) is a form of bone marrow failure. It usually results from a

cytotoxic T cell attack on the marrow stem cell. Two treatments can be used for SAA. One is allogeneic hematopoietic stem cell transplant (HSCT). The other is immunosuppressive treatment (IST). In most cases, HSCT or IST works. But for some people, clonal evolution occurs after IST. One of the most common forms of clonal evolution is chromosome 7 abnormalities. These have a poor prognosis. HSCT can be used to treat them. Researchers do not know why clonal evolution happens. They want to look at data from past studies to learn more.

Objective:

To compare the data of people with SAA who developed chromosome 7 abnormalities between those who ultimately received HSCT versus those who received chemotherapy alone or supportive care.

Eligibility:

Adults and children with SAA who were enrolled on NHLBI protocol 12-H-0150, 06-H-0034, 03-H-0249, 03-H-0193, 00-H-0032, or 90-H-0146

Design:

This study uses data from past studies. The participants in those studies have allowed their data to be used in future research.

Researchers will review participants medical records. They will collect clinical data, such as notes, test results, and imaging scans. They will also collect the research data gathered as part of the original study.

Researchers will enter the data into an in-house database. It is password protected. All data will be kept in secure network drives or in sites that comply with NIH security rules.

Other studies may be added in the future.

Study Overview

• Status: Completed
• Conditions: Severe Aplastic Anemia

Detailed Description

Severe aplastic anemia (SAA) is a form of bone marrow failure in most cases is the result of a cytotoxic T cell attack on the marrow stem cell. It is effectively treated in most patients with either immunosuppressive treatment (IST) or allogeneic hematopoietic stem cell transplant (HSCT). However, after IST, 'clonal evolution' is a significant complication in about 15% of patients, presenting as either a new cytogenetic abnormality or morphological evidence of myeloid malignancy. In particular, the development of chromosome 7 abnormalities is considered high risk and is associated with poor prognosis. The optimal treatment of chromosome 7 abnormalities following SAA is not defined though HSCT is widely offered.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Heart, Lung and Blood Institute (NHLBI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

SAA Subjects who developed chromosome 7 abnormalities

Description

• Subjects will not be recruited for this study. This is a retrospective chart review.

Patients who opted out of future use of data on their prior studies will be excluded from this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
SAA patients with Monosomy 7; Severe Aplastic Anemia Patients who Developed High Risk Clonal Evolution with Chromosome 7 Abnormalities after Immunosuppressive Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities	To compare characteristics and outcomes of SAA patients who developed chromosome 7 abnormalities between those who ultimately received HSCT versus those who received chemotherapy alone or supportive care	Between the Period of 1990 to 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory value	To identify clinical predictors for the development of chromosome 7 abnormalities such as age, gender, baseline laboratory values, time from diagnosis to initial treatment, relapse, and number of IST treatments	Between the Period of 1990 to 2020
Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype	Ascertain the natural history of patients with a chromosome 7 abnormality on karyotype who were surveilled until the development of an overt myeloid neoplasm	Between the Period of 1990 to 2020
Morphological predictors in the bone marrow for progression to an overt myeloid neoplasm	To identify morphological predictors in the bone marrow for progression to an overt myeloid neoplasm in those with without an overt myeloid neoplasm at the time of development of chromosome 7 abnormalities	Between the Period of 1990 to 2020

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2020
• Primary Completion (ACTUAL): April 22, 2021
• Study Completion (ACTUAL): March 15, 2022

Study Registration Dates

• First Submitted: June 17, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (ACTUAL): June 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Natural History; Cytogenic Abnormality
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Congenital Abnormalities; Anemia; Anemia, Aplastic
• Other Study ID Numbers: 999920118; 20-H-N118