Impact of Donor-Specific anti-HLA antibodies and donor KIR characteristics in haploidentical HSCT for beta-Thalassemia
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Keywords
Haploidentical HSCT, KIR receptors, anti-HLA antibodies
Abstract
In the present study we investigated the role of donor specific HLA antibodies (DSA) and donor KIR repertoire characteristics in a group of 18 patients affected by haemoglobinopathies who underwent haploidentical T cell depleted transplantation. Among these patients, 8 rejected the transplant while 10 had complete donor chimerism (CC). Five out of 8 patients (62.5%) who rejected graft had anti-HLA antibodies in the sera collected before transplant, while only 1 patient out of 10 (10%) with CC showed their presence (p=0,042). Notably, of the 5 HLA antibodies positive patients who rejected the graft 3 had DSA (2 for class I and 1 for class I and II) while none of the patients with CC had DSA. Among the 8 patients that experienced graft failure 4 were transplanted with a donor characterized by the lack of NK alloreactivity and 5 with a donor with a B content value <2. Although we analyzed a small cohort of patients, our data indicated that the presence of anti-HLA antibodies in patient sera, but not donor KIR characteristics, correlates with graft failure thus suggesting that analysis of anti-HLA antibodies should be taken into account in haploidentical transplant setting.
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References
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18 - Muccio L, Bertaina A, Falco M, Pende D, Meazza R, Lopez-Botet M, Moretta L, Locatelli F, Moretta A, Della Chiesa M. Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing ??+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies. Haematologica. 2016 Mar;101(3):371-81. doi: 10.3324/haematol.2015.134155
19 - Falco M, Moretta L, Moretta A, Bottino C. KIR and KIR ligand polymorphism: a new area for clinical applications? Tissue Antigens. 2013 Dec;82(6):363-73. doi: 10.1111/tan.12262. Review.
20 - Mancusi A, Ruggeri L, Velardi A. Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood. 2016 Oct 3. pii: blood-2016-07-730564.
2 - Li Pira G, Malaspina D, Girolami E, Biagini S, Cicchetti E, Conflitti G, Broglia M, Ceccarelli S, Lazzaro S, Pagliara D, Meschini A, Bertaina A, Montanari M, Locatelli F. Selective Depletion of ?? T Cells and B Cells for Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency.Biol Blood Marrow Transplant. 2016 Nov;22(11):2056-2064. doi: 10.1016/j.bbmt.2016.08.006.
3 - Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev ClinOncol. 2016;13(2):132.
4 - Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F. HLA-haploidentical stem cell transplantation after removal of alphabeta + T and B-cells in children with non-malignant disorders. Blood. 2014;124(5):822–6.
5 - Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, Rapanotti MC, Sarmati L, Bavaro P, Papalinetti G, Di Nicola M, Papola F, Montanari M, Nagler A, Arcese W. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013 Jan 31;121(5):849-57. doi: 10.1182/blood-2012-08-453399. Epub 2012 Nov 19.
6 - Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Grasso R, Pozzi S, Colombo N, Tedone E, Varaldo R, Raiola AM. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015 Jun;50Suppl 2:S37-9. doi: 10.1038/bmt.2015.93
7- Locatelli F, Merli P, Strocchio L. Transplantation for thalassemia major: alternative donors. Curr Opin Hematol. 2016 Nov;23(6):515-523.
8 - Tolar J, Sodani P, Symons H. Alternative donor transplant of benign primary hematologic disorders. Bone Marrow Transplant. 2015 May;50(5):619-27. doi: 10.1038/bmt.2015.1. Review.
9 - Sodani P, Isgrò A, Gaziev J, Paciaroni K, Marziali M, Simone MD, Roveda A, De Angelis G, Gallucci C, Torelli F, Isacchi G, Zinno F, Landi F, Adorno G, Lanti A, Testi M, Andreani M, Lucarelli G. T cell-depleted hla-haploidentical stem cell transplantation in thalassemia young patients. Pediatr Rep. 2011 Jun 22;3Suppl 2:e13. doi: 10.4081/pr.2011.s2.e13
10 - Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, Wang X, Thall PF, Champlin RE, Fernandez-Vina M. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009 Oct 27;88(8):1019-24. doi: 10.1097/TP.0b013e3181b9d710.
11 - Focosi D, Zucca A, Scatena F. The role of anti-HLA antibodies in hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2011 Nov;17(11):1585-8. doi: 10.1016/j.bbmt.2011.06.004. Review.
12 - Chang YJ, Zhao XY, Xu LP, Zhang XH, Wang Y, Han W, Chen H, Wang FR, Mo XD, Zhang YY, Huo MR, Zhao XS, Y K, Liu KY, Huang XJ. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulatedhaploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. J Hematol Oncol. 2015 Jul 10;8:84
13 - Morin-Zorman S, Loiseau P, Taupin JL, Caillat-Zucman S. Donor-Specific Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2016 Aug 12;7:307. doi: 10.3389/fimmu.2016.00307. Review.
14 - Giorgio La Nasa, Adriana Vacca, Roberto Littera, Eugenia Piras, Sandro Orru, Marianna Greco, Carlo Carcassi, Giovanni Caocci. What unrelated hematopoietic stem cell transplantation in thalassemia taught us about transplant Immunogenetics. In press in MJHID,DOI: 10.4084/mjhid.2016.048
15 - Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SG, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P, Miller JS. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood 2010 Oct 7;116(14):2411-9. doi: 10.1182/blood-2010-05-283051. Epub 2010 Jun 25.
16 - Littera R, Orrù N, Vacca A, Bertaina A, Caocci G, Mulargia M, Giardini C, Piras E, Mastronuzzi A, Vinti L, Orrù S, Locatelli F, Carcassi C, La Nasa G. The role of killer immunoglobulin-like receptor haplotypes on the outcome of unrelated donor haematopoietic SCT for thalassaemia. Bone Marrow Transplant. 2010 Nov;45(11):1618-24. doi: 10.1038/bmt.2010.24. Epub 2010 Feb 22.
17 - Mancusi A, Ruggeri L, Urbani E, Pierini A, Massei MS, Carotti A, Terenzi A, Falzetti F, Tosti A, Topini F, Bozza S, Romani L, Tognellini R, Stern M, Aversa F, Martelli MF, Velardi A. Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces non-relapse mortality. Blood. 2015;125(20):3173–82.
18 - Muccio L, Bertaina A, Falco M, Pende D, Meazza R, Lopez-Botet M, Moretta L, Locatelli F, Moretta A, Della Chiesa M. Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing ??+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies. Haematologica. 2016 Mar;101(3):371-81. doi: 10.3324/haematol.2015.134155
19 - Falco M, Moretta L, Moretta A, Bottino C. KIR and KIR ligand polymorphism: a new area for clinical applications? Tissue Antigens. 2013 Dec;82(6):363-73. doi: 10.1111/tan.12262. Review.
20 - Mancusi A, Ruggeri L, Velardi A. Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood. 2016 Oct 3. pii: blood-2016-07-730564.