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Anti-HLA donor-specific antibodies in allogeneic stem cell transplantation: management and desensitization protocol

Bone Marrow Transplantation volume 54, pages 1717–1720 (2019)Cite this article

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The role of antibodies directed against the human leukocyte antigen (HLA) system has been well analyzed in rejection of solid organ transplantations [1, 2] and in transfusion medicine [3]. In the setting of allogeneic hematopoietic stem cells transplantation (HSCT), only in the recent years their importance has been better defined, even though anti-HLA antibodies are frequently detectable in hematologic patients, due to sensitization from multiple transfusions, usually before the introduction of online universal leukoreduction, previous transplantations, and pregnancies in female patients.

In 1989, Anasetti et al. [4] showed that the incompatibility for HLA-B and HLA-DR, and a positive complement-dependent cytotoxicity assay for anti-donor lymphocytotoxic antibody were independent risk factors associated with graft failure (GF) after an allo-HSCT. Since then, different experiences have suggested the role of antibodies directed against donor-specific HLA loci (DSA) as a risk factor for GF and graft rejection [5,6,7,8,9,10]. In case of DSAs detection, the selection of an alternative donor, if available and feasible, or the planning of an immunosuppressive strategy, to decrease the DSA levels, are required. So far, there is no standardized immunosuppression method to manage the presence of DSAs in HSCT [11]. We hereby report the incidence of anti-HLA antibodies and DSAs, and the results of the desensitization strategy employed at the Hematology Center and Immunohematology and Transfusion Medicine Unit of the “Sapienza” University in Rome. From August 2014 to January 2017, we prospectively screened for anti-HLA antibodies 65 consecutive patients who were candidates for a mismatched HSCT and 9 donors who had had immunologic events. The search for anti-HLA antibodies was carried out using the multianalyte bead assay, with the Luminex platform (Luminex, Austin, TX), including Lifecode Screen and LSA I/II (Immucor, Inc., Norcross, Georgia). The results were expressed as mean fluorescence intensity (MFI); a MFI > 1000 was considered positive. The analysis was performed 40–30 days before the transplant date. In case of a mismatched related donor, a flow cytometric cross-match test was performed.

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References

  1. Kissmeyer-Nielsen F, Olsen S, Petersen VP, Fjeldborg O. Hyperacute rejection of kidney allografts, associated with preexisting humoral antibodies against donor cells. Lancet. 1966;2:662–5.

    Article  CAS  Google Scholar 

  2. Zachary AA, Leffell MS. Barriers to successful transplantation of the sensitized patient. Expert Rev Clin Immunol. 2010;6:449–60.

    Article  Google Scholar 

  3. Hod E, Schwartz J. Platelet transfusion refractoriness. Br J Haematol. 2008;142:348–60.

    Article  Google Scholar 

  4. Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, et al. Effect of HLA compatibility on engraftment of bone marrow in patients with leukemia or lymphoma. N Engl J Med. 1989;320:197–204.

    Article  CAS  Google Scholar 

  5. Yoshihara S, Maruya E, Taniguchi K, Kaida K, Kato R, Inoue T, et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transplant. 2012;47:508–15.

    Article  CAS  Google Scholar 

  6. Ciurea SO, Thall PF, Wang X, Wang S, Hu Y, Cano P, et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood. 2011;118:5957–64.

    Article  CAS  Google Scholar 

  7. Cutler C, Kim HT, Sun L, Sese D, Glotzbecker B, Armand P, et al. Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood. 2011;118:6691–7.

    Article  CAS  Google Scholar 

  8. Spellman S, Bray R, Rosen-Bronson S, Haagenson M, Klein J, Flesch S, et al. The detection of donor-directed, HLA-specific alloantibodies in recipients of un-related hematopoietic cell transplantation is predictive of graft failure. Blood. 2010;115:2704–8.

    Article  CAS  Google Scholar 

  9. Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009;88:1019–24.

    Article  CAS  Google Scholar 

  10. Gladstone DE, Zachary AA, Fuchs EJ, Luznik L, Kasamon YL, King KE, et al. Partially mismatched transplantation and human leukocyte antigen donor-specific antibodies. Biol Blood Marrow Transplant. 2013;19:647–52.

    Article  CAS  Google Scholar 

  11. Zachary AA, Leffell MS. Desensitization for solid organ and hematopoietic stem cell transplantation. Immunol Rev. 2014;258:183–207.

    Article  CAS  Google Scholar 

  12. Morin-Zorman S, Loiseau P, Taupin JL, Caillat-Zucman S. Donor-specific anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;12:307.

    Google Scholar 

  13. Seftel MD, Growe GH, Petraszko T, Benny WB, Le A, Lee CY. Universal prestorage leukoreduction in Canada decreases platelet alloimmunization and refractoriness. Blood. 2004;103:333–9.

    Article  CAS  Google Scholar 

  14. Ciurea SO, Cao K, Fernadez-Vina M, Kongtim P, Malki MA, Fuchs E, et al. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the detection and treatment of donor-specific anti-HLA antibodies (DSA) in haploidentical hematopoietic cell transplantation. Bone Marrow Transplant. 2018;53:521–34. https://doi.org/10.1038/s41409-017-0062-8.

    Article  CAS  PubMed  Google Scholar 

  15. Nordlander A, Uhlin M, Ringdén O, Kumlien G, Hauzenberger D, Mattsson J. Immune modulation to prevent antibody-mediated rejection after allogeneic hematopoietic stem cell transplantation. Transplant Immunol. 2011;25:153–1588.

    Article  CAS  Google Scholar 

  16. Kongtim P1, Cao K, Ciurea SO. Donor specific anti-HLA antibody and risk of graft failure in haploidentical stem cell transplantation. Adv Hematol. 2016;2016:4025073.

    PubMed  PubMed Central  Google Scholar 

  17. Ciurea SO, Thall PF, Milton DR, Barnes TH, Kongtim P, Carmazzi Y, et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1392–8.

    Article  CAS  Google Scholar 

  18. Narimatsu H, Wake A, Miura Y, Tanaka H, Matsumura T, Takagi S, et al. Successful engraftment in crossmatch-positive HLA-mismatched peripheral blood stem cell transplantation after depletion of antidonor cytotoxic HLA antibodies with rituximab and donor platelet infusion. Bone Marrow Transplant. 2005;36:555–6.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Hematology, Policlinico Umberto 1, “Sapienza” University, Rome, Italy

    Ursula La Rocca, Walter Barberi, Giovanni Fernando Torelli, Luisa Quattrocchi, Roberto Ricci, Robin Foà & Anna Paola Iori

  2. Immunohematology and Transfusion Medicine Unit, Policlinico Umberto 1, “Sapienza” University, Rome, Italy

    Maria Paola Perrone, Paola Cinti, Maria Gozzer, Mahnaz Shafii Baftii, Paola Gesuiti, Roberto Lattanzi, Claudio Cavallari, Luca Laurenti & Gabriella Girelli

  3. GIMEMA Foundation, Rome, Italy

    Alfonso Piciocchi

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Correspondence to Ursula La Rocca.

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La Rocca, U., Perrone, M.P., Piciocchi, A. et al. Anti-HLA donor-specific antibodies in allogeneic stem cell transplantation: management and desensitization protocol. Bone Marrow Transplant 54, 1717–1720 (2019). https://doi.org/10.1038/s41409-019-0497-1

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