Single-cell analysis of somatic mutations to understand and improve blood formation after hematopoietic stem cell transplantatio

Completed

Conditions: Hematopoietic stem cell transplantation
bone marrow transplantation
10002086
10021460
10024324

Registration Number: NL-OMON54736

Lead Sponsor: Prinses Máxima Centrum voor Kinderoncologie

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

Patients (n=30):
- Recipients of an allogeneic hematopoietic stem cell transplantation (HSCT)
from an umbilical cord blood donor (n=10), adult haplo donor (n=10), or healthy
sibling donor (n=10)
- Age at HSCT <18 yrs
- First HSCT
- >95% donor chimerism at the time of blood sampling
- Currently alive
- No major HSCT-related complications (see exclusion criteria),

Healthy subjects (n=20):
- Healthy donors of the sibling and haplo-HSCT recipients described above.

Exclusion Criteria

- Major HSCT-related complications, such as >grade 2 graft versus host disease.
- Secondary graft failure
- Objection to be notified about actionable findings from whole-genome
sequencing.
- Failure of the HSCT recipient, donor and/or their legal representatives to
understand the patient information and informed consent form (either due to
intellectual disability or to language problems). Of note: For sibling and
haplo transplants, we will only include subjects in whom both the HSCT
recipient and his/her donor (and, if applicable, their caregivers) agree to
participate in the current study.

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Our main study endpoints are:<br /><br>- The total number of somatic mutations acquired after HSCT in the HSCT<br /><br>recipient and his/her donor;<br /><br>- The frequency of HSC clones contributing to production of each of the mature<br /><br>blood lineages in the HSCT recipient and donor.<br /><br>- The impact of donor age on the number of HSC clones that contribute to<br /><br>post-transplant hematopoiesis, and the genomic integrity of these cells</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary study outcomes are:<br /><br>- Identification of potential causes of HSC mutagenesis upon HSCT, assessed by<br /><br>mutational signature analysis<br /><br>- Insight into the cellular and molecular pathways that guide HSC<br /><br>(non-)engraftment</p><br>