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Hematopoietic SCT from Partially HLA-mismatched (HLA-haploidentical) Related Donors

Overview
Specialty General Surgery
Date 2008 Aug 6
PMID 18679375
Citations 15
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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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References
1.
OReilly R, Keever C, Kernan N, Brochstein J, Collins N, Flomenberg N . HLA nonidentical T cell depleted marrow transplants: a comparison of results in patients treated for leukemia and severe combined immunodeficiency disease. Transplant Proc. 1987; 19(6 Suppl 7):55-60. View

2.
Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H . Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006; 81(10):1390-7. DOI: 10.1097/01.tp.0000214462.63943.14. View

3.
Nguyen S, Kuentz M, Vernant J, Dhedin N, Bories D, Debre P . Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation. Leukemia. 2007; 22(2):344-52. DOI: 10.1038/sj.leu.2405041. View

4.
Miller J, Soignier Y, Panoskaltsis-Mortari A, McNearney S, Yun G, Fautsch S . Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005; 105(8):3051-7. DOI: 10.1182/blood-2004-07-2974. View

5.
Mavroudis D, Jiang Y, Hensel N, Lewalle P, Couriel D, Kreitman R . Specific depletion of alloreactivity against haplotype mismatched related individuals by a recombinant immunotoxin: a new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation. Bone Marrow Transplant. 1996; 17(5):793-9. View