We aim to define the growth trajectory of clonal hematopoësis after allogeneic transplantation, and identify potential modulating factors.
ID
Source
Brief title
Condition
- Haematological disorders NEC
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary aim of this study is to determine the growth trajectories of
post-transplant clonal hematopoiesis, expressed as the changes in variant alele
frequencies, and depicted graphically as trajectories over time.
Secondary outcome
We also aim to identify factors that may influence the chance of
post-transplant CH. To achieve this, we will compare clinical and clone-related
factors between HCT recipients with and without CH, one year after HCT.
Finally, using various laboratory technologies, we will investigate the
molecular processes that stimulate or inhibit the growth of CH clones.
Background summary
Hematopoietic cell transplantation (HCT) is a last-resort, potentially curative
treatment for patients with from various, otherwise lethal diseases. As
treatment strategies improve, the number of HCT survivors and their life
expectancy continue to increase, We have recently shown that pediatric
long-term HCT survivors are at increased risk of clonal hematopoiesis (CH)
compared to age-matched controls. CH is an age-related disorder which, in the
general population, is associated with an increased risk of hematologic and
cardiovascular diseases, and a decreased risk of Alzheimer's disease.
It is yet unkonwn why hematopoietic cell transplanttaion leads to a higher
incidence of CH. In addition, we don't know whether CH afte transplantation and
CH in the general population have the same health consequences. Insight into
clonal growth trajectories after HCT may identify critical periods during which
mutant stem cells preferentially expand, to identify potential modulating
factors and to better predict the risk of future malignant transformation.
Study objective
We aim to define the growth trajectory of clonal hematopoësis after allogeneic
transplantation, and identify potential modulating factors.
Study design
This is an observational, prospective, explorative study in children and
adolescents/young adults undergoing allogeneic hematopoietic cell
transplantation in the Princess Máxima Center. Study participants will donate
one or multiple extra blood tubes, at various time points from before to long
after HCT. Study blood sampling will be combined with planned blood collections
for clinical care.
Clonal hematopoiesis will be assessed using a targeted sequencing panel of 38
CH driver mutations. The presence or absence of CH, and the size of the
observed clones, will be studied over time and related to clinical factors
(e.g., stem cell source). In addition, using various molecular technologies, we
will study the fundamental mechanisms influencing the growth patterns of
post-transplant CH.
Study burden and risks
This study requires pediatric and young adult recipients, as their
post-transplant survival exceeds that of older adult HCT recipients
by several decades, posing unique challenges on the integrity and longevity of
the engrafted HSCs. In addition, as clinical HCT
regimens differ between children and adults (e.g. composition of the cell
product, use of irradiation, chemotherapy dose), results obtained in adult HCT
recipients cannot be translated directly to children.
This study will provide unique insights into the dynamics of clonal
hematopoiesis after transpantation, while posing minimal risks to the
participants. Results from this study may contribute to the development of
therapeutic strategies to influence the growth of CH clones, after
transplantation as well as in the general population.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
Planned for first allogeneic HCT in the Princess Máxima Center.
Exclusion criteria
- Failure of the HCT recipient and/or their legal representative to understand
the patient information and informed consent form (either because of
intellectual disability or language barriers).
- Recipients of pharma-sponsored, genetically modified cell products (e.g.,
Bluebird Bio)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87692.041.24 |