PRESENCE OF KIR2DS1 RECEPTOR IN DONORS OF ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION DUE TO MYELOID MALIGNANCIES IMPROVES OVERALL SURVIVAL IN RECIPIENTS WITH HLA-C2 ANTIGENS
Author(s): ,
Andras Bors
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Katalin Piroska Kiss
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Hajnalka Andrikovics
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Sara Benko
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Zsuzsanna Illes
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Dora Inotai
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Aniko Szilvasi
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Adrienn Gelle-Hosso
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Katalin Rajczy
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
,
Zoltan Csukly
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Arpad Batai
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Eva Torbagyi
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Aniko Barta
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Lilla Lengyel
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Peter Remenyi
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
,
Tamas Masszi
Affiliations:
St. Istvan and St. Laszlo Hospital,Budapest,Hungary
Attila Tordai
Affiliations:
Hungarian National Blood Transfusion Service,Budapest,Hungary
EHA Learning Center. Tordai A. Jun 13, 2015; 100835
Disclosure(s): Hungarian National Blood Transfusion Service
Dr. Attila Tordai
Dr. Attila Tordai

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Abstract
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Abstract: P694

Type: Poster Presentation

Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45

Location: Poster area (Hall C)

Background
Recognition of HLA-C2 antigen of recipient cells by the activating killer immunoglobulin like receptor (KIR), KIR2DS1 receptor on donor natural killer (NK) cell may lead to increased graft versus leukemia effect in patients with myeloid malignancies treated by allogeneic hematopoietic transplantation (HSCT) influencing disease free (DFS) and overall survival (OS).

Aims
The goal of the present study was to examine the effect of donor KIR status in conjunction with recipient HLA-C type on the outcome of HSCT.

Methods
In our cohort, 249 consecutive adult patients, who underwent first allogeneic HSCT (HLA-identical sibling n=117 and unrelated donor n=132) for a malignant myeloid condition, namely acute myeloid leukemia (AML, n=157), bi-phenotypic acute leukemia (n=10), chronic myeloid leukemia (n=24), myeloproliferative neoplasm (n=23) and myelodysplastic syndrome (n=35) at a single center between 2007 and 2013, were retrospectively analyzed. Median follow-up was 36 months (range 6-92 months). Genotyping for the presence of KIR genes was performed by an allele specific multiplex PCR using archived DNA samples. Low resolution HLA-C typing was performed by sequence specific oligonucleotides as part of the routine work-up prior to HSCT.

Results
The frequency of the donor KIR2DS1 gene in the entire cohort was 36.5% (91/249) while the distribution of HLA-C1/C2 groups was as follows: HLA-C1: 36.5% (91/249), HLA-C1/C2: 47.4% (118/249), HLA-C2: 16.1% (40/249). There was no difference in DFS or OS between patient subgroups stratified by the presence or absence of KIR2DS1 or HLA-C1/C2. As expected, patients with sibling donors showed significantly better DFS and OS. Further analyzes were performed exclusively focusing on the patient subgroup with KIR2DS1 positive donors (n=91). Within this subgroup, we found improved DFS and OS for patients carrying at least one copy of the HLA-C2 antigen (i.e. HLA-C2 homozygous and heterozygous patients combined, n=54) compared to those homozygous for the HLA-C1 antigen (n=47). DFS at 3 years for HLA-C2 carriers was 55.9% compared to HLA-C1 homozygotes with 39.4% (p=0.14). Similar comparison for OS showed 62.3% for the former and 42.3% for the latter subgroup (p=0.068). Upon performing a further stratification, we performed an identical comparison exclusively for the AML patient subgroup (HLA-C2 carriers: n=36 and HLA-C1 homozygous: n=22) indicating a 3 years DFS of 60.4% for HLA-C2 carriers compared to 45.1% for HLA-C1 homozygotes (p=0.19) and a 3 years OS of 71.7% for the former and 45.7% for the latter (p=0.047). In spite of the impressive differences of the above survival rates, due to the low case numbers, only OS among AML patients with KIR2DS1 and HLA-C2 combination was significantly better. Performing a multivariate analyzes by Cox regression among AML-patients considering age, sex, the type of conditioning (myeloablative or reduced intensity conditioning) and type of donor as covariates, the association of a favorable OS with the simultaneous presence of KIR2DS1 and HLA-C2 remained significant (hazard ratio=0.422, 95% confidence interval: 0.179-0.995, p=0.049).

Summary
Our results indicate that the combination of donor KIR2DS1 and recipient HLA-C2 may be a favorable genetic constellation in allogeneic HSCT for AML with respect to overall survival.

Keyword(s): Allogeneic hematopoietic stem cell transplant, HLA, Killer immunoglobulin receptors (KIR), Survival

Session topic: Stem cell transplantation - Experimental
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