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

Study Overview
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Brief Summary
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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

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

Conditions
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Stem Cell Transplantation, Haplo-identical

Intervention / Treatment
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* Other: Assessment of the Allogenomic Mismatch Score (AMS)
* Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| no acute GVH, no chronic GVH<br> | Other: Assessment of the Allogenomic Mismatch Score (AMS)<br>* 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.<br>Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)<br>* 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).<br>|
| acute GVH without chronic GVH<br> | Other: Assessment of the Allogenomic Mismatch Score (AMS)<br>* 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.<br>Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)<br>* 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).<br>|
| chronic GVH without acute GVH<br> | Other: Assessment of the Allogenomic Mismatch Score (AMS)<br>* 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.<br>Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)<br>* 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).<br>|
| acute and chronic GVH<br> | Other: Assessment of the Allogenomic Mismatch Score (AMS)<br>* 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.<br>Other: Assessment of the optimised Allogenomic Mismatch Score (AMS)<br>* 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).<br>|

What is the study measuring?
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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 |