Clinical trial NCT05243498: Allogenomic Mismatch Score (AMS) Applied to Haplo-identical Donor/Recipient Pairs in Haematopoietic Stem Cell Transplantation
Official title: Allogenomic Mismatch Score (AMS) Applied to Haplo-identical Donor/Recipient Pairs in Haematopoietic Stem Cell Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stem Cell Transplantation
Haplo-identical
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2022-02-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 40 haplo-identical donor/recipient pairs

Brief summary: The occurrence of acute and/or chronic GVH (Graf Versus Host disease) for recipients undergoing HSCT (haematopoietic stem cell transplantation) with a geno-identical donor suggests the implication of other systems or genes than those involved in HLA (Human Leukocyte Antigen) compatibility.

In kidney transplantation, it has been shown that the AMS (allogenomic mismatch score) is correlated with the probability of survival of the graft. This AMS reflects the degree of differences between the immunopeptidomes of the recipient and his donor as it is a continuous variable based on the number of nsSNP (non synonymous Single Nucletotide Polymorphism) between the donor and the recipient. Roughly, the exome of the donor is aligned to the exome of the recipient, allowing to count the number of variations that will generate a peptide present in the recipient but absent in in the donor. In this case, peptide presented by the recipient's cells is not part of the donor's immunopeptidome, leading to an activation of the donor's immunocompetent cells toward this antigen, i.e. to alloreactivity that may cause GVL (Graft Versus Leukemia) and/or GVH.

This study aims to highlight significant correlations between the occurrence of acute and/or chronic GVH after haplo-identical stem cell transplantation and the AMS.

This would allow to use the AMS as a predictive factor of acute or chronic GVH, which could be employed to select the best donor for one particular recipient and/or personalize the immunotherapies after transplantation


Eligibility criteria: Inclusion Criteria:

* - Recipients who underwent haplo-identical stem cell transplantation in CHRU (Centre Hospitalier Régional et Universitaire) de Nancy
* Recipients transplanted between 03/01/2015 et 01/01/2020
* Recipient older than 18 years old at time of transplant
* Available DNA for the recipient and his donor.

Exclusion Criteria:

* Recipient died within the 6 months following the transplantation without acute GVH (unknown status for one of the measured outcomes)

Primary outcomes:
measure: Predictive performance of AMS regarding the occurence of chronic GVH
timeFrame: 12 months after each transplantation
Secondary outcomes:
measure: Predictive performance of AMS regarding the occurence of acute GVH
timeFrame: 6 months after each transplantation
measure: Predictive performance of an optimised AMS regarding the occurence of chronic GVH
timeFrame: 12 months after each transplantation
measure: Predictive performance of an optimised AMS regarding the occurence of acute GVH
timeFrame: 6 months after each transplantation
measure: Predictive performance of AMS regarding the occurence of relapse
timeFrame: 12 months after each transplantation
measure: Predictive performance of an optimised AMS regarding the occurence of relapse
timeFrame: 12 months after each transplantation
Other outcomes:
Locations:
city: Vandœuvre-lès-Nancy
country: France
facility: Alice Aarnink
Study officials:
References: