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Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors

Bone Marrow Transplantation volume 42, pages 365–377 (2008)Cite this article

Abstract

Hematopoietic SCT from a partially HLA-mismatched (HLA-haploidentical) first-degree relative offers the benefits of rapid and near universal donor availability but also the risks that result from traversing the HLA barrier; namely, graft failure, severe GVHD and prolonged immunodeficiency. Improvements over the last 10 years in conditioning regimens, graft engineering and pharmacological immunoprophylaxis of GVHD have substantially reduced the morbidity and mortality of HLA-haploidentical SCT. Highly immunosuppressive but nonmyeloablative conditioning extends the availability of HLA-haploidentical SCT to elderly hematologic malignancy patients lacking HLA-matched donors and permits recovery of autologous hematopoiesis in the event of graft failure. Current regimens for HLA-haploidentical SCT are associated with a 2-year non-relapse mortality of 20±5%, relapse of 35±15% and overall survival of 50±20%. Major developmental areas include harnessing natural killer cell alloreactivity to reduce the risk of disease relapse and improving immune reconstitution by delayed infusions of lymphocytes selectively depleted of alloreactive cells. Hematologic malignancy patients who lack suitably matched related or unrelated donors can now be treated with HLA-haploidentical related donor or unrelated umbilical cord blood SCT. Future clinical trials will assess the relative risks and benefits of these two graft sources.

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Acknowledgements

This study was supported by Grant 1KL2RR025006-01 to HJS from the National Center for Research Resources and P01 CA15396 to EJF from the National Cancer Institute. EJF is a Clinical Research Scholar of the Leukemia and Lymphoma Society of America.

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  1. Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    H J Symons

  2. Department of Oncology, Cancer Immunology and Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    E J Fuchs

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Symons, H., Fuchs, E. Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors. Bone Marrow Transplant 42, 365–377 (2008). https://doi.org/10.1038/bmt.2008.215

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