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KIR and HLA genotypes have no identifiable role in single-unit dominance following double-unit umbilical cord blood transplantation

Bone Marrow Transplantation volume 50, pages 150–152 (2015)Cite this article

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Umbilical cord blood (CB) is widely used as an alternative hematopoietic stem cell source. The use of double-unit CB grafts is a common strategy to augment graft cell dose and successfully leads to engraftment by a single unit.1,2 Current evidence suggests that unit dominance is T-cell mediated;3, 4, 5 a role for natural killer (NK) cells, however, is not excluded. NK cells mediate murine BM allograft rejection and are the first lymphocytes to reconstitute following CB transplantation (CBT).6,7 In addition, CB NK cells are of a mature phenotype and have high cytotoxic and proliferative capacity.6, 7, 8, 9 We, therefore, tested the hypothesis that unit dominance after double-unit CBT results from an immune interaction mediated by NK cells between the two CB units or between the recipient and the infused units.

This is a retrospective analysis of 83 recipients of double-unit CBT treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between October 2005 and July 2010 for hematological malignancies (46 (55.4%) acute leukemia, 32 (38.5%) lymphoma and 5 (6%) other). Sixty-six (80%) patients received a myeloablative conditioning regimen. All patients received immunosuppression with a calcineurin inhibitor and mycophenolate mofetil. The median age of patients was 35.6 years (0.9–64.6). Informed consent for specimen collection was obtained from the patients or legal guardians in accordance with MSKCC review board guidelines. CB unit dominance was determined by molecular testing for donor chimerism from BM and/or peripheral blood samples obtained at serial time points starting from day +21 through 1 year following CBT. Unit dominance was established for all patients by day +100.

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Acknowledgements

We would like to acknowledge the adult and pediatric bone marrow transplantation teams at Memorial Sloan-Kettering Cancer Center, Christina Castellan for her help in the collection of clinical data, Anne Marie Gonzales and Rebecca Hawke for verifying the clinical and HLA data, and Nabila Noor for her assistance with KIR genotyping. This study was supported in part by the National Institute of Health (P01-CA023766, R01-HL088134, U01-AI069197).

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Author notes

  1. N Tarek & M M Gallagher

    Present address: Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.,

  2. urrent address: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Authors and Affiliations

  1. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    N Tarek

  2. Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    M M Gallagher

  3. Department of Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    J F Chou & G Heller

  4. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    M N Lubin, J N Barker & K C Hsu

  5. Weill Medical College of Cornell University, New York, NY, USA

    J N Barker & K C Hsu

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  1. N Tarek
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Correspondence to K C Hsu.

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Tarek, N., Gallagher, M., Chou, J. et al. KIR and HLA genotypes have no identifiable role in single-unit dominance following double-unit umbilical cord blood transplantation. Bone Marrow Transplant 50, 150–152 (2015). https://doi.org/10.1038/bmt.2014.218

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