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

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

Study Overview

• Status: Completed
• Conditions: Stem Cell Transplantation; Haplo-identical
• Intervention / Treatment: Other: Assessment of the Allogenomic Mismatch Score (AMS); Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• France
  • Vandœuvre-lès-Nancy, France, 54500
    • Alice Aarnink

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

40 haplo-identical donor/recipient pairs

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
no acute GVH, no chronic GVH	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.; Other: 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).
acute GVH without chronic GVH	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.; Other: 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).
chronic GVH without acute GVH	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.; Other: 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).
acute and chronic GVH	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.; Other: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2015
• Primary Completion (Actual): November 6, 2020
• Study Completion (Actual): November 6, 2020

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2021PI066

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No