KIR Sequencing and Typing for Allograft in Nancy

Stem Cell Transplant Complications Clinical Trial

— KIR-STAN  

Official title:

Application of the Major Predictive Scoring Strategies Assessing KIR-based NK Alloreactivity to Donor/Recipient Couples

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04882605
• Other study ID #: 2020PI142
• Status: Completed
• Start date: March 23, 2015
• Est. completion date: July 25, 2019

Study information

• Verified date: May 2021
• Source: Central Hospital, Nancy, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: July 25, 2019
• Est. primary completion date: July 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

COHORT 1 = Matched Sibling Donors couples (MSD couples) INCLUSION CRITERIA

• 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

• 16 couples without any sign of GVH (8 males and 8 females)

• 16 couples with aGVH without cGVH

• 9 couples with cGVH without aGVH

• 9 couples with both cGVH and aGVH. EXCLUSION CRITERIA

• insufficient DNA material after Miltenyi extraction

COHORT 2 = Haploidentical couples INCLUSION CRITERIA

• patient undergoing a haploidentical HSCT in the Hematology Department of Nancy's University Hospital, Lorraine, France (French Minister registration number : DC-2020-4068) EXCLUSION CRITERIA

• insufficient DNA material after Miltenyi extraction (7 MSD couples)

Related Conditions & MeSH terms

• Stem Cell Transplant Complications

Intervention

Genetic:
• MHC typing
Allelic genotyping resolution of MHC genes (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1, -DPB1 and -DRB3/4/5) using Illumina technology.
• KIR typing
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.
• Assessment of KIR-based prediction scores
Compiling donor/recipient MHC and KIR typings into 28 major KIR-based prediction scores

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France	University of Cambridge

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Describe the heterogeneity of the major KIR-based prediction models in assessing alloreactivity		At inclusion
Primary	Describe the potential correlations between a KIR-based prediction models and post-allograft outcomes		at least 4 months