KIR Sequencing and Typing for Allograft in Nancy
KIR-STAN
Application of the Major Predictive Scoring Strategies Assessing KIR-based NK Alloreactivity to Donor/Recipient Couples
1 other identifier
observational
156
0 countries
N/A
Brief Summary
The use of haploidentical donors for aHSCT has greatly increased this past decade leading to a major paradigm shift: while finding 10/10 HLA-matched donors represented the prior difficulty for decades, the current problem is about finding the best haploidentical donor among several potential ones. The prediction of NK cells alloreactivity toward leukemic cells provides promising perspectives, although the underlying biological processes remain unclear. To date, many prediction models based on KIR and MHC genotyping have been designed and used across studies, which contribute to blur clinical conclusions. The investigators hypothesized that the diversity of models used to predict NK alloreactivity in aHSCT could partly be responsible for the current literature discrepancies. The main objective of this work consisted of applying the major KIR-based prediction models in D/R couples undergoing aHSCT in different fashions - with MSD and haploidentical donors - to describe their heterogeneity and potential correlations. As clinical data were available for these two cohorts, the investigators described correlations that could be assessed between the scoring strategies and the clinical outcomes. As suspected, it was highlighted that the different scoring strategies greatly impact the assessment of alloreactivity within D/R couples. As an example, two broadly used scoring strategies - educational models and missing-ligand models - show clear opposite predictions. Moreover, some scoring strategies seem to be better adapted to genoidentical or haploidentical cohorts, whereas others are robust across the different cohorts. Concerning the clinical-biological correlations, it was highlighted that (i) each scoring strategy is differentially associated to the different outcomes (ii) the different scoring strategies predict one particular outcome with different efficacy (iii) the D/R compatibility greatly impacts the pertinence of the scoring strategy. This work therefore contributes to unravel the KIR-based alloreactivity prediction of NK cells in aHSCT. This would help to overcome the current literature discrepancies in this field as in making new hypotheses to better understand and predict NK alloreactivity to further develop its use in medical practice.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Mar 2015
Longer than P75 for all trials
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 23, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 25, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 25, 2019
CompletedFirst Submitted
Initial submission to the registry
May 4, 2021
CompletedFirst Posted
Study publicly available on registry
May 12, 2021
CompletedMay 12, 2021
May 1, 2021
4.3 years
May 4, 2021
May 9, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity
At inclusion
Describe the potential correlations between a KIR-based prediction models and post-allograft outcomes
at least 4 months
Study Arms (2)
Donor/recipient couple with Matched Sibling Donor
Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation \+ its 10/10 HLA-matched donor recruited among his siblings
Donor/recipient couple with Haploidentical Donor
Donor/recipient couple = Patient undergoing a hematopoietic stem cell transplantation \+ its 5/10 HLA-matched donor recruited among his relatives
Interventions
Allelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology.
Allelic genotyping resolution of all 13 KIR genes (KIR2DL1, KIR2DL2/2DL3, KIR2DL4, KIR2DL5A, KIR2DL5B, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS3/2DS5, KIR2DS4, KIR3DL1/3DS1, KIR3DL2, KIR3DL3), 2 KIR pseudogenes (KIR2DP1 and -3DP1) using Illumina technology.
Compiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores
Eligibility Criteria
Two independents cohorts of D/R couples (i) Matched siblig donors (MSD) couples : 50 couples selected from the French national database CRYOSTEM (ii) Haploidentical donors couples: exhaustive local cohort of haploidentical HSCT performed in the Hematology Department of Nancy's University Hospital, Lorraine, France. French Minister registration number : DC-2020-4068
You may qualify if:
- recipient of HSCT selected from the French national database CRYOSTEM
- adult patients (18-50 years old)
- transplanted in first remission
- receiving myeloablative conditioning without anti-thymoglobulin
- couples without any sign of GVH (8 males and 8 females)
- couples with aGVH without cGVH
- couples with cGVH without aGVH
You may not qualify if:
- insufficient DNA material after Miltenyi extraction
- insufficient DNA material after Miltenyi extraction (7 MSD couples)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Central Hospital, Nancy, Francelead
- University of Cambridgecollaborator
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- OTHER
- Target Duration
- 4 Months
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2021
First Posted
May 12, 2021
Study Start
March 23, 2015
Primary Completion
July 25, 2019
Study Completion
July 25, 2019
Last Updated
May 12, 2021
Record last verified: 2021-05