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Post-Transplant Events

Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors

Bone Marrow Transplantation volume 47, pages 817–823 (2012)Cite this article

Abstract

The impact of activating KIR (aKIR) and inhibitory KIR (iKIR) on OS, relapse-related mortality (RRM) and acute GVHD (aGVHD) was prospectively studied in 84 adults with high-risk hematologic malignancies receiving reduced intensity conditioning (RIC) T-cell depleted hematopoietic SCT (HSCT) from haploidentical related donors. In this clinical model, freedom from RRM is dependent on GVL effect. Patients were divided into myeloid (n=49) and lymphoid (n=35) malignancy groups. KIR-ligand and ligand-ligand models were studied in both GVH and rejection directions and statistically correlated with outcome measures. In the myeloid group, OS was higher (P=0.009) and RRM was lower (P=0.036) in patients missing HLA-C group2 ligand to donor iKIR. OS was higher if patients had >1 missing ligand (P=0.018). In lymphoid malignancy, missing ligand to donor KIR had no impact on OS or RRM. However, OS was better with donor aKIR 2DS2 (P=0.028). There was a trend towards shorter OS in recipient with KIR 2DS1, 2DS5 and 3DS1, although sample sizes were too small to provide inferential statistics. Findings in lymphoid malignancy patients should be further studied. These results suggest that the absence of appropriate HLA ligands in the recipient to donor iKIR may induce GVL without aGVHD in myeloid malignancy patients undergoing TCD-RIC transplants.

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Acknowledgements

NJC is supported by PO1 (NJC) 2PO1-CA047741-16A1 from NIH; DAR is a Leukemia Lymphoma Society Scholar in Clinical Research.

Author contribution: VKP conceptualized and designed the study, collected clinical data, analyzed the data, wrote the manuscript and led all the coordination efforts; DAR and NJC were involved with conceptualizing, designing and overseeing the study, development of the transplant protocol, collection of clinical data and manuscript preparation; DFC was involved in conceptualizing the study, generation of HLA and KIR typing data in the laboratory, data analysis and editing the manuscript; GB was involved in statistical analysis, review of the data and manuscript preparation; NLR was involved with conceptualizing the study, laboratory support and manuscript preparation; ADO and AC contributed to laboratory studies; KMS, JPC, MEH, CG and GDL were involved with the collection of clinical data and manuscript preparation; YY contributed in manuscript preparation.

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Author notes

  1. D-F Chen and V K Prasad: These authors contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Pathology, Clinical Transplantation Immunology Laboratory, Duke University Medical Center (DUMC), Durham, NC, USA

    D-F Chen, A DeOliveira & A Clark

  2. Department of Pediatrics, Blood and Marrow Transplantation Division, DUMC, Durham, NC, USA

    V K Prasad

  3. Department of Biostatistics, DUMC, Durham, NC, USA

    G Broadwater

  4. HLA Laboratory, Cedars-Sinai Health Systems, Los Angeles, CA, USA

    N L Reinsmoen

  5. Division of Cellular Therapy, Department of Medicine, DUMC, Durham, NC, USA

    K M Sullivan, J P Chute, M E Horwitz, C Gasparetto, G D Long, Y Yang, N J Chao & D A Rizzieri

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  1. D-F Chen
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Correspondence to V K Prasad.

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Chen, DF., Prasad, V., Broadwater, G. et al. Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors. Bone Marrow Transplant 47, 817–823 (2012). https://doi.org/10.1038/bmt.2011.181

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