Phylodynamics of allogeneic haematopoietic stem cell transplantation
Research type
Research Study
Full title
Stem cell dynamics in human allogeneic transplantation through phylogenetic tracking of single-cell somatic mutations
IRAS ID
268341
Contact name
Peter Campbell
Contact email
Sponsor organisation
Wellcome Sanger Institute
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Allogeneic haematopoietic stem cell transplantation (HSCT) is an established treatment for blood diseases, including blood cancers and genetic blood disorders. Over 40,000 HSCTs are performed in Europe every year. Haematopoietic stem cells (HSCs) are stem cells collected from bone marrow which give rise to, or generate, other blood cells. During the HSCT procedure, HSCs are harvested from a donor before being infused via intravenous therapy into a recipient, who will have undergone chemotherapy and/or radiotherapy to prepare for the donor cells.
Although HSCT represents the only potential treatment for many patients with blood cancers who have received a poor prognosis, HSCT carries significant risks, and has a treatment-related mortality (TRM) of 20-30% in the first 3 months following treatment. Other serious complications can include low blood counts, graft failure (recipient's body does not accept the stem cells), graft-versus-host-disease (the recipient's cells attack the transplanted stem cells) and immunosuppression (a reduction in the effectiveness of the recipient's immune system). There is therefore scope for significant improvements to be made to the treatment.
This study aims to better understand how transplanted blood stems cells grow and develop in the recipient by studying mutations in cells. We will recruit 8-12 related patients undergoing HSCT, and their donors, and collect a series of blood samples. We may also collect bone marrow and other tissue samples from the recipients, if it is appropriate and safe to do so during their routine care. Particular cells will be isolated, grown into cell cultures, and analysed by whole-genome sequencing and other techniques. It is hoped that this research will enable further research to be undertaken into HSCT and the associated outcomes and complications.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
19/LO/1390
Date of REC Opinion
28 Aug 2019
REC opinion
Favourable Opinion