DONOR KIR3DL1/RECEPTOR HLA-BW4-80I COMBINATION REDUCES ACUTE LEUKEMIA RELAPSE AFTER UMBILICAL CORD BLOOD TRANSPLANTATION WITHOUT IN VITRO T-CELL DEPLETION KIR3DL1 with HLA-Bw4-80I reduces leukemia relapse

Main Article Content

xinchen fang
Zimin Sun
Huilan Liu
Xiang Wan
Wen Yao
Kaidi Song
Kaidi Song
Baolin Tang
Xiaoyu zhu
Jun Peng

Keywords

acute myeloid leukemia, natural killer cells, killer immunoglobulin-like receptors, umbilical cord blood transplantation,acute lymphocytic leukemia

Abstract

Background: Donor natural killer (NK) cell alloreactivity in umbilical cord bone marrow transplantation (UCBT) can lead to leukemic relapse. However, NK cell function is calibrated by interaction with human leukocyte antigens (HLAs). This study aimed to investigate graft-resistant leukemia after transplantation and compared specific genotypes of killer immunoglobulin-like receptors (KIRs) in donors and human leukocyte antigen ligands in patients.


Methods: We retrospectively analyzed 232 patients with acute leukemia from a single center. Patients had undergone UCBT with myeloablative conditioning and without anti-thymocyte globulin. We identified the KIR genotypes of cord blood donors using polymerase chain reaction with sequence-specific primers. All of the donors contained KIR3DL1.


Results: The patients were divided into three groups according to the HLA-B locus. The donor KIR3DL1 and recipient HLA-Bw4-80I combination was predictive of being highly educated, and was associated with a lower relapse (P = 0.006) and better overall survival (probability of relapse = 0.13, P < 0.001) than the uneducated group. We found no significant increase in the incidence of acute or chronic graft-versus-host disease.


Conclusions: Our data suggest that the donor KIR3DL1/receptor and HLA-Bw4-80I combination in UCBT results in stronger graft-versus-leukemia effects and improved outcomes in patients with acute leukemia.

Downloads

Download data is not yet available.
Abstract 485 | PDF Downloads 112 HTML Downloads 44

References

1. Pasquini M, Wang Z, Horowitz MM, Gale RP. 2013 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders. Clin Transpl. 2013: 187-97.
2. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990; 75: 555–62
3. Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA. Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood. 2002; 100: 1935–47
4. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002; 295: 2097–100.
5. Middleton D, Gonzelez F. The extensive polymorphism of KIR genes. Immunology. 2010; 129: 8–19.
6. McQueen KL, Parham P. Variable receptors controlling activation and inhibition of NK cells. Curr Opin Immunol. 2002 Oct; 14(5): 615-21.
7. Anfossi N1, André P, Guia S, Falk CS, Roetynck S, Stewart CA et al. Human NK cell education by inhibitory receptors for MHC class I. Immunity. 2006 Aug; 25(2): 331-42. Epub 2006 Aug 10.
8. Boudreau JE1, Giglio F1, Gooley TA1, Stevenson PA1, Le Luduec JB1, Shaffer BC et al. KIR3DL1/HL A-B subtypes govern acute myelogenous leukemia relapse after hematopoietic cell transplantation. J Clin Oncol. 2017 Jul 10; 35(20): 2268-2278.
9. O’Connor, G.M. and McVicar, D. The Yin-Yang of KIR3DL1/S1: molecular mechanisms and cellular function. Crit.Rev. Crit Rev Immunol. 2013; 33(3): 203-18.
10. Boudreau JE1, Giglio F1, Gooley TA1, Stevenson PA1, Le Luduec JB1, Shaffer BC1 et al. KIR3DL1/HLA-B subtypes govern acute myelogenous leukemia relapse after hematopoietic cell transplantation. J Clin Oncol. 2017 Jul 10; 35(20): 2268-2278.
11. Bern MD1,2, Beckman DL1, Ebihara T3, Taffner SM1, Poursine-Laurent J3, White JM4 et al. Immunoreceptor tyrosine-based inhibitory motif-dependent functions of an MHC class I-specific NK cell receptor. Proc Natl Acad Sci U S A. 2017 Oct 3; 114(40): E8440-E8447.
12. Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA. Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood. 2002; 100: 1935–47.
13. Ruggeri L1, Mancusi A, Burchielli E, Capanni M, Carotti A, Aloisi T et al. NK cell alloreactivity and allogeneic hematopoietic stem cell transplantation. Blood Cells Mol Dis. 2008 Jan-Feb; 40(1): 84-90.
14. Stringaris K1, Adams S, Uribe M, Eniafe R, Wu CO, Savani BN et al. Donor KIR Genes 2DL5A, 2DS1 and 3DS1 are associated with a reduced rate of leukemia relapse after HLA identical sibling stem cell transplantation for acute myeloid leukemia but not other hematologic malignancies. Biol Blood Marrow Transplant. 2010; 16(9): 1257-1264
15. Sahin U, Dalva K, Gungor F, Ustun C, Beksac M. Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation. Ann Hematol. 2018 Jun; 97(6): 1027-1039.
16. Hoseinian SA, Jafari D, Mahmoodi M, Alimoghaddam K, Ostadali M, Talebzadeh Bonakdar A, et al. The impact of donor and recipient KIR genes and KIR ligands on the occurrence of acute graft-versus-host disease and graft survival after HLA-identical sibling hematopoietic stem cell transplantation. Turk J Med Sci. 2018 Aug 16; 48(4): 794-804.
17. Moesta AK1, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P. Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol. 2008 Mar 15; 180(6): 3969-79.
18. Dunphy SE1, Guinan KJ2, Chorcora CN1, Jayaraman J3, Traherne JA4, Trowsdale J5 et al. 2DL1, 2DL2 and 2DL3 all contribute to KIR phenotype variability on human NK cells. Genes Immun. 2015 Jul-Aug; 16(5): 301-10.
19. Cooley S1, Trachtenberg E, Bergemann TL, Saeteurn K, Klein J, Le CT et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009; 113(3): 726-732.
20. Erbe AK1, Wang W1, Reville PK1, Carmichael L2, Kim K2, Mendonca EA et al. HLA-Bw4-I-80 isoform differentially influences clinical outcome as compared to HLA-Bw4-T-80 and HLA-A-Bw4 isoforms in rituximab or dinutuximab-based cancer immunotherapy. Front Immunol. 2017 Jun 12; 8: 675.