KIR Sequencing and Typing for Allograft in Nancy (KIR-STAN)

Central Hospital, Nancy, France

Status

Completed

Conditions

Stem Cell Transplant Complications

Treatments

Genetic: KIR typing

Genetic: MHC typing

Genetic: Assessment of KIR-based prediction scores

Study type

Observational

Funder types

Other

Identifiers

NCT04882605

2020PI142

Details and patient eligibility

About

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.

Enrollment

156 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)