IC-06. Impact of killer cell Immunoglobulin-like receptor–ligand mismatching on the outcomes of haploidentical hematopoietic stem cell transplantation
Zoya V. Konova, Elena N. Parovichnikova, Ekaterina G. Khamaganova, Igor Yu. Uribin, Mikhail Yu. Drokov, Natalia N. Popova, Ulyana V. Maslikova, Feruza A. Omarova, Ekaterina D. Mikhaltsova, Olga M. Koroleva, Anna A. Dmitrova, Mariya V. Dovydenko, Olga S. Starikova, Darya S. Dubnyak, Elmira I. Kolgaeva, Mobil I. Akhmedov, Vera A. Vasilyeva, Tatyana V. Gaponova, Denis V. Kamelskikh, Irina V. Galtseva, Larisa A. Kuzmina, Valery G. Savchenko
National Research Center for Hematology, Moscow, Russia
Contact: Dr. Zoya V. Konova, e-mail: konova.zoya@gmail.com
Summary
Introduction
Natural killer (NK) cells are an essential part of the innate immune system directed against malignancy and infections. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. In terms of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), donor NK cells may become activated against residual leukemic cells when the host lacks a ligand that is present in the donor. Our aim was to evaluate the impact of donor versus recipient killer cell immunoglobulin-like receptor (KIR)-ligand mismatch (KIR-Lmm) on the outcomes of haplo-HSCT in patients with hematological malignances.
Patients and methods
We explored the impact of KIR ligand mismatching in 43 patients (20 males/23 females) with acute myeloid leukemia (AML, n=18), acute lymphoblastic leukemia (ALL, n=17), diffuse large B cell lymphoma (DLBCL, n=2), chronic myeloid leukemia (CML, n=1) and myelodysplastic syndrome (MDS, n=5) who underwent haplo-HSCT at the National Research Center for Hematology between July 2016 and December 2019. Median age of the patients was 29 (18-58) years. All patients underwent haplo-HSCT with in vivo (using post-transplant cyclophosphamide (PT-Cy), n=16) or ex vivo (with previous TCR alpha/beta depletion, n=27) T cell depletion. Median follow-up was 14.5 months. Patient’s characteristics are summarized in table 1. HLA-genotype was determined by PCR-SBT (sequence based typing) in all donors and recipients included in this study. Presence or absence of the functional KIR genes tested by KIR Genotyping SSP Kit. The probabilities of OS and DFS were estimated using the Kaplan-Meier method, and univariate comparisons were assessed using the log-rank test. A p<0.05 was considered significant.
Table 1. Patient’s characteristics
Results
In our study, 24 out of 43 patients had KIR/KIR-ligand mismatch (KIR-Lmm). Statistical analysis revealed that the presence of KIR-Lmm may significantly improve relapse-free survival (RFS) (85% vs 36%, p=0.0131, Fig. A) and decrease probability of relapse (15% vs 55%, р=0.1029, Fig. B) and non-relapse mortality (NRM) (0% vs 17%, р=0.0437, Fig. C), but the difference in overall survival (OS) was not significant (68% vs 54.6%, p=0.0770, Fig. D). However, the improvement in the graft-versus-leukemia (GVL) effect was not associated with an increase in both acute (KIR-Lmm – 21% vs no KIR-Lmm – 26%, p=0.6733, Fig. E) and chronic GVHD (18% vs 10.5%, p=0.5777, Fig. F) probabilities.
Figure 1. Effects of KIR receptors and their ligands upon the outcomes of HSCT from haploidentical donors (A, relapse-free survival; B, relapse rates; C, non-relapse mortality; D, overall survival; E, aGVHD probability; chronic GVHD probability)
Conclusions
RFS was significantly better in patients who had KIR-Lmm. This may be explained in part by earlier NK cell recovery after transplantation, compensating the lack of efficient T cells, which is important in terms of haplo-HSCT with previous TCR alpha/beta depletion. Our findings show that KIR-Lmm in donor versus recipient direction could provide better disease control after haplo-HSCT while avoiding GVHD and NRM.
Keywords
Killer cell immunoglobulin-like receptors, haploidentical hematopoietic stem cell transplantation.
