Allogenomic Mismatch Score (AMS) Applied to Haplo-identical Donor/Recipient Pairs in Haematopoietic Stem Cell Transplantation

Stem Cell Transplantation Clinical Trial

— AMS-haplo  

Official title:

Allogenomic Mismatch Score (AMS) Applied to Haplo-identical Donor/Recipient Pairs in Haematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05243498
• Other study ID #: 2021PI066
• Status: Completed
• Start date: March 23, 2015
• Est. completion date: November 6, 2020

Study information

• Verified date: February 2022
• Source: Central Hospital, Nancy, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 6, 2020
• Est. primary completion date: November 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Stem Cell Transplantation

Intervention

Other:
• Assessment of the Allogenomic Mismatch Score (AMS)
Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP 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 the donor.
• Assessment of the optimised Allogenomic Mismatch Score (AMS)
Optimised Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP between the donor and the recipient, encountering only peptides that can be presented by the donors' MHC (using another layer of algorithm, NetMHCpan).

Locations

Country	Name	City	State
France	Alice Aarnink	Vandœuvre-lès-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictive performance of AMS regarding the occurence of chronic GVH	Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP 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 the donor. The comparison of AMS will be performed between the groups "presence of cGVH" and "absence of cGVH"	12 months after each transplantation
Secondary	Predictive performance of AMS regarding the occurence of acute GVH	Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP 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 the donor. The comparison of AMS will be performed between the groups "presence of aGVH" and "absence of aGVH"	6 months after each transplantation
Secondary	Predictive performance of an optimised AMS regarding the occurence of chronic GVH	Optimised Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP between the donor and the recipient, encountering only peptides that can be presented by the donors' MHC (using another layer of algorithm, NetMHCpan). The comparison of optimised AMS will be performed between the groups "presence of cGVH" and "absence of cGVH"	12 months after each transplantation
Secondary	Predictive performance of an optimised AMS regarding the occurence of acute GVH	Optimised Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP between the donor and the recipient, encountering only peptides that can be presented by the donors' MHC (using another layer of algorithm, NetMHCpan). The comparison of optimised AMS will be performed between the groups "presence of aGVH" and "absence of aGVH"	6 months after each transplantation
Secondary	Predictive performance of AMS regarding the occurence of relapse	Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP 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 the donor. The comparison of AMS will be performed between the groups "relapse" and "no relapse"	12 months after each transplantation
Secondary	Predictive performance of an optimised AMS regarding the occurence of relapse	Optimised Allogenomic Mismatch Score (AMS) is a continuous variable based on the number of nsSNP between the donor and the recipient, encountering only peptides that can be presented by the donors' MHC (using another layer of algorithm, NetMHCpan). The comparison of optimised AMS will be performed between the groups "relapse" and "no relapse"	12 months after each transplantation