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ID
Source
Brief title
Health condition
Allogeneic hematopoietic stem cell transplantation
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoints are: (1) The total number of somatic mutations acquired after HSCT in the HSCT recipient and his/her donor; (2) The frequency of HSC clones contributing to production of each of the mature blood lineages in the HSCT recipient and donor.
Secondary outcome
Secondary outcomes are: (3) Identification of potential causes of HSC mutagenesis upon HSCT; (4) Generation of an experimental method to retrospectively assess the impact of common clinical parameters (donor age, conditioning regimen, etc) on HSC integrity.
Background summary
Hematopoietic stem cell transplantation (HSCT) is a last-resort curative therapy for patients suffering from various, otherwise lethal, diseases. The success of this therapy relies critically on adminstration of sufficient numbers of donor HSCs. However, due to lack of strategies to count and trace human HSCs, the number of engrafting HSCs and their long-term contribution to hematopoiesis remain elusive.
Here, we will use innovative technology, which employs single-cell analysis of naturally occurring genetic mutations to retrospectively reconstruct the number of HSCs clones, their quantitative contributions to each of the mature blood lineages and their mutational burden in human allo-HSCT recipients and their donors.
This is a fundamental, observational study. We will include 10 HSCT recipients transplanted at pediatric age, and their healthy donors. The study intervention is a single blood collection of 10 mL venous blood.
Study objective
Hematopoiesis after transplantation is supported by a limited number of HSCs, and the proliferative stress posed upon these cells compromises their long-term genomic and functional integrity,
Study design
One randomly selected time point after HSCT
Intervention
N/a
Mirjam Belderbos
0650006518
m.e.belderbos@prinsesmaximacentrum.nl
Mirjam Belderbos
0650006518
m.e.belderbos@prinsesmaximacentrum.nl
Inclusion criteria
(1) Allogeneic HSCT with bone marrow cells from a healthy sibling donor; (2) Age at HSCT <18 yrs; (3) First HSCT; (4) Availability of viably frozen donor bone marrow cells from the Biobank of the UMC Utrecht; (5) >95% donor chimerism; (6) No major HSCT-related complications (see exclusion criteria).
Exclusion criteria
(1) Major HSCT-related complications, such as >grade 2 graft versus host disease; (2) Secondary graft failure; (3) Objection to be notified about actionable findings from whole-genome sequencing; (4) 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: 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 are eligible.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL7584 |
| Other | METC Utrecht : METC12345 |