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,
ID
Bron
Verkorte titel
Aandoening
Allogeneic hematopoietic stem cell transplantation
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
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.
Achtergrond van het onderzoek
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.
Doel van het onderzoek
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,
Onderzoeksopzet
One randomly selected time point after HSCT
Onderzoeksproduct en/of interventie
N/a
Publiek
Mirjam Belderbos
0650006518
m.e.belderbos@prinsesmaximacentrum.nl
Wetenschappelijk
Mirjam Belderbos
0650006518
m.e.belderbos@prinsesmaximacentrum.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
(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).
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
(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.
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7584 |
| Ander register | METC Utrecht : METC12345 |