Impact of Donor-Specific anti-HLA antibodies and donor KIR characteristics in haploidentical HSCT for beta-Thalassemia

Marco Andreani, Manuela Testi, Pietro Sodani, Maria Troiano, Andrea Di Luzio, Giuseppe Testa, Michela Falco, Elvira Poggi, Javid Gaziev, Antonina Piazza
  • Marco Andreani
    Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata; Rome, Italy;, Italy | m.andreani@fondazioneime.org
  • Manuela Testi
    Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata; Rome, Italy;, Italy
  • Pietro Sodani
    International Center for Transplantation in Thalassemia and Sickle Cell Anemia, IME Foundation at Polyclinic of Tor Vergata, Rome, Italy, Italy
  • Maria Troiano
    Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata; Rome, Italy;, Italy
  • Andrea Di Luzio
    Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata; Rome, Italy;, Italy
  • Giuseppe Testa
    Laboratory of Immunogenetics and Transplant Biology; IME Foundation at Polyclinic of Tor Vergata; Rome, Italy;, Italy
  • Michela Falco
    Laboratory of Clinical and Experimental Immunology, GianninaGaslini Institute, Genoa, Italy, Italy
  • Elvira Poggi
    Laboratory of Tissue Typing and Transplant Immunology, National Council of Researches IFT Unit of Rome S. Camillo Hospital – Regional Transplant Center Lazio, Rome, Italy, Italy
  • Javid Gaziev
    International Center for Transplantation in Thalassemia and Sickle Cell Anemia, IME Foundation at Polyclinic of Tor Vergata, Rome, Italy, Italy
  • Antonina Piazza
    Laboratory of Tissue Typing and Transplant Immunology, National Council of Researches IFT Unit of Rome S. Camillo Hospital – Regional Transplant Center Lazio, Rome, Italy, Italy

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.

Keywords

Haploidentical HSCT, KIR receptors, anti-HLA antibodies

Full Text:

PDF
HTML
Submitted: 2016-12-05 18:02:46
Published: 2017-03-01 00:00:00
Search for citations in Google Scholar
Related articles: Google Scholar

References

- Gaziev J, Marziali M, Isgrò A, Sodani P, Paciaroni K et al.Gallucci C, Andreani M, Testi M, De Angelis G, Alfieri C, Cardarelli L, Ribersani M, Armiento D, Lucarelli. Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach. Blood. 2013 Oct 10;122(15):2751-6. doi: 10.1182/blood-2013-07-513473. Epub 2013 Aug 20.

- 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 αβ 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.

- Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev ClinOncol. 2016;13(2):132.

- 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.

- 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.

- 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

- Locatelli F, Merli P, Strocchio L. Transplantation for thalassemia major: alternative donors. Curr Opin Hematol. 2016 Nov;23(6):515-523.

- 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.

- 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

- 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.

- 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.

- 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

- 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.

- 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

- 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.

- 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.

- 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.

- 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 αβ+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

- 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.

- 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.

Abstract views:
459

Views:
PDF
99
HTML
160

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM


Copyright (c) 2017 Mediterranean Journal of Hematology and Infectious Diseases

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

The Mediterranean Journal of Hematology and Infectious Diseases [eISSN 2035-3006] is owned by the U.C.S.C. and it is published by PAGEPress®, Pavia, Italy. All credits and honors to PKP for their OJS.
 
 
© PAGEPress 2008-2017     -     PAGEPress is a registered trademark property of PAGEPress srl, Italy.     -     VAT: IT02125780185