Donor selection: Histocompatibility and immunogenetics
DOI:
https://doi.org/10.46765/2675-374X.2025v7n1e369Keywords:
Histocompatibility Testing, Donor Selection, Hematopoietic Stem Cell Transplantation, Graft Rejection, Graft vs Host DiseaseAbstract
Background: Histocompatibility factors have long influenced donor selection, a key component of allogeneic hematopoietic cell transplantation (HCT). Objective: To update the 2021 consensus recommendations on histocompatibility and donor selection by the Sociedade Brasileira de Terapia Celular e Transplante de Medula Óssea (SBTMO). Methods: We conducted a thorough literature review and compiled current evidence on HLA factors in contemporary HCT. Results: This review highlights the current impact of histocompatibility factors in allogeneic HCT, including donor-specific anti-HLA antibodies (DSA), high-resolution HLA mismatching, and HLA-DPB1 permissiveness on HCT outcomes. Additionally, it highlights how non-HLA factors, including donor age, the use of post-transplant cyclophosphamide, the timing of HCT, and donor availability, influence histocompatibility and affect donor prioritization. It also presents current alternative donor selection algorithms and addresses emerging topics, such as the significance of HLA loss of heterozygosity following relapse post-HCT. Conclusion: The present article provides a comprehensive overview of the current role of HLA factors in modern allogeneic HCT.
References
1. Barriga F, Lima ACM. Donor selection in allogeneic stem cell transplantation. Curr Opin Hematol. 2024; 31(6):261–9. https://doi.org/10.1097/MOH.0000000000000831 DOI: https://doi.org/10.1097/MOH.0000000000000831
2. Spellman SR. Hematology 2022—what is complete HLA match in 2022? Hematology. 2022;2022(1):83–9. https://doi.org/10.1182/hematology.2022000326 DOI: https://doi.org/10.1182/hematology.2022000326
3. Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, Chabannon C, Kuball J, Basak GW, Dufour C, Galimard JE, Polge E, Lankester A, Montoto S, Snowden JA, Styczynski J, Yakoub-Agha I, Mohty M, Nagler A. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. The Lancet Haematology. 2019;6(11):e573–e584. https://doi.org/10.1016/S2352-3026(19)30158-9 DOI: https://doi.org/10.1016/S2352-3026(19)30158-9
4. Jimenez Jimenez AM, Spellman SR, Politikos I, McCurdy SR, Devine SM, Al Malki MM, Bolon YT, Lee SJ, Dehn J, Pidala J, Maiers M, Askar M, Malmberg C, Auletta JJ, Stefanski H, Broglie L, Qayed M, Horwitz M, Wilder JS, Gooptu M, Mehta RS, Fernandez-Viña M, Shaw BE, Shaffer BC. Allogeneic hematopoietic cell donor selection: contemporary guidelines from the NMDP/CIBMTR. Transplant Cell Ther. 2025;31(12):973–88. https://doi.org/10.1016/j.jtct.2025.07.004 DOI: https://doi.org/10.1016/j.jtct.2025.07.004
5. Lee SJ, Logan B, Horowitz MM, Dehn JG, Pidala J, Grunwald MR, Westervelt P, Farhadfar N, Hogan WJ, Bashey A, Hayes-Lattin B, Hill L, Brunstein C, Arai S, Srour SA, Symons H, Uberti J, Vasu S, Pusic I, Juckett M, Leifer E, He N, Devine S, Shaw BE, Ciurea SO. Primary results from Blood and Marrow Transplant Clinical Trials Network 1702: clinical transplant-related long-term outcomes of alternative donor allogeneic transplantation. J Clin Oncol. 2025:43(31):3369–80. https://doi.org/10.1200/JCO-25-00206 DOI: https://doi.org/10.1200/JCO-25-00206
6. Arrieta-Bolaños E, Lima ACM, Andreani M, De Santis D, Malard F, Mayor NP, Mehta RS, Meisel R, Pagliuca S, Petersdorf E, Piemontese S, Sacchi N, Santoro N, Sanz J, Schetelig J, Spellman SR, Onida F, Sánchez-Ortega I, Mohty M, Yakoub-Agha I, Fleischhauer K, Ruggeri A. HLA matching in contemporary haematopoietic cell transplantation: Recommendations from the EBMT Practice Harmonisation and Guidelines Committee. Bone Marrow Transplant. 2026;61(8):1015–23. https://doi.org/10.1038/s41409-026-02922-0 DOI: https://doi.org/10.1038/s41409-026-02922-0
7. Yu N, Askar M, Wadsworth K, Gragert L, Fernández-Viña MA. Current HLA testing recommendations to support HCT. Human Immunology. 2022;83(10):665–73. https://doi.org/10.1016/j.humimm.2022.04.008 DOI: https://doi.org/10.1016/j.humimm.2022.04.008
8. Torres MA, Rampim GF, Cardoso JF, Vergueiro C, Pereira NF, Lima ACM. Donor selection: immunogenetics and histocompatibility. JBMTCT. 2021;2(1):22–7. https://doi.org/10.46765/2675-374X.2021v4n1p22-27 DOI: https://doi.org/10.46765/2675-374X.2021v4n1p22-27
9. Bettinotti MP. Evolution of HLA testing for hematopoietic stem cell transplantation: Importance of the candidate’s antibody profile for donor selection. Human Immunology. 2022;83(10):721–9. https://doi.org/10.1016/j.humimm.2022.04.012 DOI: https://doi.org/10.1016/j.humimm.2022.04.012
10. Kongtim P, Vittayawacharin P, Zou J, Srour S, Shaffer B, Shapiro RM, Varma A, McGuirk J, Dholaria BR, McCurdy SR, DeZern AE, Bejanyan N, Bashey A, Furst S, Castagna L, Mariotti J, Ruggeri A, Bailen R, Teshima T, Xiao-Jun H, Bonfim C, Aung F, Cao K, Carpenter PA, Hamadani M, Askar M, Fernandez-Vina M, Girnita A, Ciurea SO. ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies. Transplant Cell Ther. 2024;30(12):1139–54. https://doi.org/10.1016/j.jtct.2024.09.005 DOI: https://doi.org/10.1016/j.jtct.2024.09.005
11. Xie Y, Parekh J, Tang Z, Wu D, Wu X. Donor-specific antibodies and primary graft failure in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transplant Cell Ther. 2021;27(8):687.e1–687.e7. https://doi.org/10.1016/j.jtct.2021.04.030 DOI: https://doi.org/10.1016/j.jtct.2021.04.030
12. Huang Y, Luo C, Wu G, Huang X, Ding Y, Huang Z, Chen J, Li X, Xu S. Effects of donor-specific antibodies on engraftment and long-term survival after allogeneic hematopoietic stem cell transplantation-A systematic review and meta-analysis. Bone Marrow Transplant. 2023;58(5):544–51. https://doi.org/10.1038/s41409-023-01932-6 DOI: https://doi.org/10.1038/s41409-023-01932-6
13. Liu M, Kang Z, Zhang H. Impacts of donor-specific anti-HLA antibodies on post-transplant clinical outcomes in hematopoietic stem cell transplantation: A systematic review and meta-analysis. Transpl Immunol. 2025;92:102275. https://doi.org/10.1016/j.trim.2025.102275 DOI: https://doi.org/10.1016/j.trim.2025.102275
14. Ciurea SO, Thall PF, Wang X, Wang SA, Hu Y, Cano P, Aung F, Rondon G, Molldrem JJ, Korbling M, Shpall EJ, de Lima M, Champlin RE, Fernandez-Vina M. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood. 2011;118(22):5957–64. https://doi.org/10.1182/blood-2011-06-362111 DOI: https://doi.org/10.1182/blood-2011-06-362111
15. Ciurea SO, Thall PF, Milton DR, Barnes TH, Kongtim P, Carmazzi Y, López AA, Yap DY, Popat U, Rondon G, Lichtiger B, Aung F, Afshar-Kharghan V, Ma Q, Fernández-Viña M, Champlin RE, Cao K. Complement-binding donor-specific anti-hla antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21(8):1392–8. https://doi.org/10.1016/j.bbmt.2015.05.001 DOI: https://doi.org/10.1016/j.bbmt.2015.05.001
16. Spellman S, Bray R, Rosen-Bronson S, Haagenson M, Klein J, Flesch S, Vierra-Green C, Anasetti C. The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure. Blood. 2010;115(13):2704–8. https://doi.org/10.1182/blood-2009-09-244525 DOI: https://doi.org/10.1182/blood-2009-09-244525
17. Fuji S, Oshima K, Ohashi K, Sawa M, Saito T, Eto T, Tanaka M, Onizuka M, Nakamae H, Shiratori S, Ozawa Y, Hidaka M, Nagamura-Inoue T, Tanaka H, Fukuda T, Ichinohe T, Atsuta Y, Ogata M. Impact of pretransplant donor-specific anti-HLA antibodies on cord blood transplantation on behalf of the Transplant Complications Working Group of Japan Society for Hematopoietic Cell Transplantation. Bone Marrow Transplant. 2020;55(4):722–8. https://doi.org/10.1038/s41409-019-0712-0 DOI: https://doi.org/10.1038/s41409-019-0712-0
18. Lima ACM, Bonfim C, Getz J, Amaral GBD, Petterle RR, Loth G, Nabhan SK, de Marco R, Gerbase-De Lima M, Pereira NF, Pasquini R. Untreated donor-specific hla antibodies are associated with graft failure and poor survival after haploidentical transplantation with post-transplantation cyclophosphamide in pediatric patients with nonmalignant disorders. Transplant Cell Ther. 2022;28(10):698.e1–698.e11. https://doi.org/10.1016/j.jtct.2022.07.019 DOI: https://doi.org/10.1016/j.jtct.2022.07.019
19. Srour SA, Kongtim P, Rondon G, Chen J, Petropoulos D, Ramdial J, Popat U, Kebriaei P, Qazilbash M, Shpall EJ, Champlin RE, Ciurea SO. Haploidentical transplants for patients with relapse after the first allograft. Am J Hematol. 2020;95(10):1187–92. https://doi.org/10.1002/ajh.25924 DOI: https://doi.org/10.1002/ajh.25924
20. Lima ACM, Bonfim C, Getz J, Dornelles LN, Amaral GB, Petterle RR, Loth G, Nabhan SK, Pereira NF, Pasquini R. The impact of donor‐specific anti‐human leukocyte antigen antibodies in salvage haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide in patients with nonmalignant disorders. HLA. 2021;97(6):493–504. https://doi.org/10.1111/tan.14277 DOI: https://doi.org/10.1111/tan.14277
21. Sullivan HC, Jaramillo A, Gaitonde S, Murphey C, Pandey S, Liu C, Jindra P, Hidalgo LG, Weimer ET, Alquist CR, Morris GP, Bray RA. Virtual crossmatching: Principles, practices, and the path forward-An American Society for Histocompatibility and Immunogenetics/College of American Pathologists collaborative. Am J Transplant. 2025;25(10):2048–56. https://doi.org/10.1016/j.ajt.2025.06.018 DOI: https://doi.org/10.1016/j.ajt.2025.06.018
22. Morris AB, Sullivan HC, Krummey SM, Gebel HM, Bray RA. Out with the old, in with the new: Virtual versus physical crossmatching in the modern era. HLA. 2019;94(6):471–81. https://doi.org/10.1111/tan.13693 DOI: https://doi.org/10.1111/tan.13693
23. Wehmeier C, Hönger G, Schaub S. Caveats of HLA antibody detection by solid-phase assays. Transplant International. 2020;33(1):18–29. https://doi.org/10.1111/tri.13484 DOI: https://doi.org/10.1111/tri.13484
24. Liwski RS, Tafulo S, Carroll R, Lan JH, Greenshields AL. Cutting through the weeds: Evaluation of a novel adsorption with crossmatch cells and elution protocol to sharpen HLA antibody identification by the single antigen bead assay. Front Genet. 2022;13:1059650. https://doi.org/10.3389/fgene.2022.1059650 DOI: https://doi.org/10.3389/fgene.2022.1059650
25. Marsh SGE, Osoegawa K, Bodmer WF, Bontrop RE, Carrington MN, Erlich HA, Heidt S, Holdsworth R, Mayr WR, Maiers M, Parham P, Petersdorf EW, Robinson J, Trowsdale J, Fernández-Viña M. Nomenclature for factors of the HLA system, 2026. HLA. 2026;107(3):e70595. https://doi.org/10.1111/tan.70595 DOI: https://doi.org/10.1111/tan.70595
26. Osoegawa K, Marsh SGE, Holdsworth R, Heidt S, Fischer G, Murphey C, Maiers M, Fernández Viña MA. A new strategy for systematically classifying HLA alleles into serological specificities. HLA. 2022; 100(3): 193–231. https://doi.org/10.1111/tan.14662 DOI: https://doi.org/10.1111/tan.14662
27. Osoegawa K, Yim K, Jeracki M, Nguyen TN, Wang L, Cho A, David R, Son J, Mankey A, Marsh SGE, Gendzekhadze K, Murphey C, Fernández Viña MA. A new strategy for systematically classifying HLA alleles into serological specificities: Update and refinement. HLA. 2024;104(4):e15702. https://doi.org/10.1111/tan.15702 DOI: https://doi.org/10.1111/tan.15702
28. Osoegawa K, Son J, Yim K, Marsh SGE, Fernández Viňa MA. Replacements at structural or functional dimorphisms 103, 109 and 167 distinguish HLA class I serologically defined antigens. HLA. 2025; 106 (3): e70387. https://doi.org/10.1111/tan.70387 DOI: https://doi.org/10.1111/tan.70387
29. Kekre N, Mak KS, Stopsack KH, Binder M, Ishii K, Brånvall E, Cutler CS. Impact of HLA-mismatch in unrelated donor hematopoietic stem cell transplantation: a meta-analysis. Am J Hematol. 2016; 91(6): 551–5. https://doi.org/10.1002/ajh.24342 DOI: https://doi.org/10.1002/ajh.24342
30. Pidala J, Lee SJ, Ahn KW, Spellman S, Wang HL, Aljurf M, Askar M, Dehn J, Fernandez Viña M, Gratwohl A, Gupta V, Hanna R, Horowitz MM, Hurley CK, Inamoto Y, Kassim AA, Nishihori T, Mueller C, Oudshoorn M, Petersdorf EW, Prasad V, Robinson J, Saber W, Schultz KR, Shaw B, Storek J, Wood WA, Woolfrey AE, Anasetti C. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood. 2014;124(16):2596–606. https://doi.org/10.1182/blood-2014-05-576041 DOI: https://doi.org/10.1182/blood-2014-05-576041
31. Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation. Blood. 2015;125(7):1189–97. https://doi.org/10.1182/blood-2014-10-604785 DOI: https://doi.org/10.1182/blood-2014-10-604785
32. Ayuk F, Beelen DW, Bornhäuser M, Stelljes M, Zabelina T, Finke J, Kobbe G, Wolff D, Wagner EM, Christopeit M, Schmid C, Ottinger H, Groth C, Faul C, Bertz H, Rachlis E, Wolschke C, Schetelig J, Horn PA, Mytilineos J, Guellstorf M, Kelsch R, Fleischhauer K, Kröger N, Bethge W. Relative impact of HLA matching and non-HLA donor characteristics on outcomes of allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2018;24(12):2558–67. https://doi.org/10.1016/j.bbmt.2018.06.026 DOI: https://doi.org/10.1016/j.bbmt.2018.06.026
33. Petersdorf EW, Carrington M, O’hUigin C, Bengtsson M, De Santis D, Dubois V, Gooley T, Horowitz M, Hsu K, Madrigal JA, Maiers MJ, Malkki M, McKallor C, Morishima Y, Oudshoorn M, Spellman SR, Villard J, Stevenson P. Role of HLA-B exon 1 in graft-versus-host disease after unrelated haemopoietic cell transplantation: a retrospective cohort study. The Lancet Haematology. 2020;7(1):e50–e60. https://doi.org/10.1016/S2352-3026(19)30208-X DOI: https://doi.org/10.1016/S2352-3026(19)30208-X
34. Arrieta-Bolaños E, Bonneville EF, Crivello P, Robin M, Gedde-Dahl T, Salmenniemi U, Kröger N, Yakoub-Agha I, Crawley C, Choi G, Broers AEC, Forcade E, Carre M, Poiré X, Huynh A, Lenhoff S, Ciceri F, Tholouli E, Schroeder T, Deconinck E, Carlson K, de Wreede LC, Hoogenboom JD, Malard F, Ruggeri A, Fleischhauer K. Human leukocyte antigen mismatching and survival in contemporary hematopoietic cell transplantation for hematologic malignancies. J Clin Oncol. 2024;42(28):3287–99. https://doi.org/10.1200/JCO.24.00582 DOI: https://doi.org/10.1200/JCO.24.00582
35. Wade JA, Hurley CK, Takemoto SK, Thompson J, Davies SM, Fuller TC, Rodey G, Confer DL, Noreen H, Haagenson M, Kan F, Klein J, Eapen M, Spellman S, Kollman C. HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation. Blood. 2007;109(9):4064–70. https://doi.org/10.1182/blood-2006-06-032193 DOI: https://doi.org/10.1182/blood-2006-06-032193
36. Spellman S, Klein J, Haagenson M, Askar M, Baxter-Lowe LA, He J, Hsu S, Blasczyk R, Hurley C. Scoring HLA class I mismatches by HistoCheck does not predict clinical outcome in unrelated hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(5):739–46. https://doi.org/10.1016/j.bbmt.2011.09.008 DOI: https://doi.org/10.1016/j.bbmt.2011.09.008
37. Duquesnoy R, Spellman S, Haagenson M, Wang T, Horowitz MM, Oudshoorn M. HLAMatchmaker-defined triplet matching is not associated with better survival rates of patients with class I HLA allele mismatched hematopoietic cell transplants from unrelated donors. Biol Blood Marrow Transplant. 2008;14(9):1064–71. https://doi.org/10.1016/j.bbmt.2008.07.001 DOI: https://doi.org/10.1016/j.bbmt.2008.07.001
38. Marino SR, Lee SM, Binkowski TA, Wang T, Haagenson M, Wang HL, Maiers M, Spellman S, van Besien K, Lee SJ, Karrison T, Artz A. Identification of high-risk amino-acid substitutions in hematopoietic cell transplantation: a challenging task. Bone Marrow Transplant. 2016;51(10):1342–9. https://doi.org/10.1038/bmt.2016.142 DOI: https://doi.org/10.1038/bmt.2016.142
39. Crivello P, Arrieta-Bolaños E, He M, Wang T, Fingerson S, Gadalla SM, Paczesny S, Marsh SGE, Lee SJ, Spellman SR, Bolon YT, Fleischhauer K. Impact of the HLA immunopeptidome on survival of leukemia patients after unrelated donor transplantation. JCO. 2023;41(13):2416–27. https://doi.org/10.1200/JCO.22.01229 DOI: https://doi.org/10.1200/JCO.22.01229
40. Fernandez-Viña MA, Wang T, Lee SJ, Haagenson M, Aljurf M, Askar M, Battiwalla M, Baxter-Lowe LA, Gajewski J, Jakubowski AA, Marino S, Oudshoorn M, Marsh SGE, Petersdorf EW, Schultz K, Turner EV, Waller EK, Woolfrey A, Umejiego J, Spellman SR, Setterholm M. Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation. Blood. 2014;123(8):1270–8. https://doi.org/10.1182/blood-2013-10-532671 DOI: https://doi.org/10.1182/blood-2013-10-532671
41. Petersdorf EW, Gooley TA, Malkki M, Bacigalupo AP, Cesbron A, Du Toit E, Ehninger G, Egeland T, Fischer GF, Gervais T, Haagenson MD, Horowitz MM, Hsu K, Jindra P, Madrigal A, Oudshoorn M, Ringdén O, Schroeder ML, Spellman SR, Tiercy JM, Velardi A, Witt CS, O’Huigin C, Apps R, Carrington M. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood. 2014; 124 (26): 3996–4003. https://doi.org/10.1182/blood-2014-09-599969 DOI: https://doi.org/10.1182/blood-2014-09-599969
42. Morishima S, Kashiwase K, Matsuo K, Azuma F, Yabe T, Sato-Otsubo A, Ogawa S, Shiina T, Satake M, Saji H, Kato S, Kodera Y, Sasazuki T, Morishima Y. High-risk HLA alleles for severe acute graft-versus-host disease and mortality in unrelated donor bone marrow transplantation. Haematologica. 2016; 101 (4): 491–8. https://doi.org/10.3324/haematol.2015.136903 DOI: https://doi.org/10.3324/haematol.2015.136903
43. Horan J, Wang T, Haagenson M, Spellman SR, Dehn J, Eapen M, Frangoul H, Gupta V, Hale GA, Hurley CK, Marino S, Oudshoorn M, Reddy V, Shaw P, Lee SJ, Woolfrey A. Evaluation of HLA matching in unrelated hematopoietic stem cell transplantation for nonmalignant disorders. Blood. 2012; 120 (14): 2918–24. https://doi.org/10.1182/blood-2012-03-417758 DOI: https://doi.org/10.1182/blood-2012-03-417758
44. Kato I, Sakaguchi H, Kato S, Sato M, Noguchi M, Yoshida N, Koh K, Koike T, Yanagimachi M, Kato K, Takahashi Y, Fujita N, Sato A, Hashii Y, Tabuchi K, Atsuta Y, Morishima S, Kanda J. Impact of human leukocyte antigen mismatch on outcomes after unrelated bone marrow transplantation in paediatric patients: A retrospective analysis by the JSTCT HLA working group. Br J Haematol. 2022;199(3):392–400. https://doi.org/10.1111/bjh.18425 DOI: https://doi.org/10.1111/bjh.18425
45. Finke J, Schmoor C, Lang H, Potthoff K, Bertz H. Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. J Clin Oncol. 2003;21(3):506–13. https://doi.org/10.1200/JCO.2003.03.129 DOI: https://doi.org/10.1200/JCO.2003.03.129
46. Ayuk F, Diyachenko G, Zabelina T, Panse J, Wolschke C, Eiermann T, Binder T, Fehse B, Erttmann R, Kabisch H, Bacher U, Kröger N, Zander AR. Anti-thymocyte globulin overcomes the negative impact of HLA mismatching in transplantation from unrelated donors. Exp Hematol. 2008;36(8):1047–54. https://doi.org/10.1016/j.exphem.2008.03.011 DOI: https://doi.org/10.1016/j.exphem.2008.03.011
47. Kröger N, Zabelina T, Binder T, Ayuk F, Bacher U, Amtsfeld G, Lellek H, Schrum J, Erttmann R, Eiermann T, Zander A. HLA-mismatched unrelated donors as an alternative graft source for allogeneic stem cell transplantation after antithymocyte globulin-containing conditioning regimen. Biol Blood Marrow Transplant. 2009;15(4):454–62. https://doi.org/10.1016/j.bbmt.2009.01.002 DOI: https://doi.org/10.1016/j.bbmt.2009.01.002
48. Kawamura K, Kanda J, Ohashi K, Fukuda T, Iwato K, Eto T, Fujiwara S, Mori T, Fukushima K, Ozawa Y, Uchida N, Ashida T, Ichinohe T, Atsuta Y, Kanda Y. Influence of HLA 1–3-locus mismatch and antithymocyte globulin administration in unrelated bone marrow transplantation. Ann Hematol. 2020; 99 (5): 1099–110. https://doi.org/10.1007/s00277-020-03995-7 DOI: https://doi.org/10.1007/s00277-020-03995-7
49. Shaw BE, Jimenez-Jimenez AM, Burns LJ, Logan BR, Khimani F, Shaffer BC, Shah NN, Mussetter A, Tang XY, McCarty JM, Alavi A, Farhadfar N, Jamieson K, Hardy NM, Choe H, Ambinder RF, Anasetti C, Perales MA, Spellman SR, Howard A, Komanduri KV, Luznik L, Norkin M, Pidala JA, Ratanatharathorn V, Confer DL, Devine SM, Horowitz MM, Bolaños-Meade J. National Marrow Donor Program–Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide. JCO. 2021;39(18):1971–82. https://doi.org/10.1200/JCO.20.03502 DOI: https://doi.org/10.1200/JCO.20.03502
50. Al Malki MM, Bo-Subait S, Logan B, Olson J, Kou J, Smith S, Leckrone E, Wu J, Stefanski HE, Auletta JJ, Spellman SR, Malmberg C, Askar M, Cusatis R, Shaffer BC, Modi D, Khimani F, Gooptu M, Hamadani M, Madbouly A, Maiers M, Fingerson S, Cook R, Ballen K, Loren A, Larkin K, Arai S, Qayed M, Choi SW, Broglie L, Shaw BE, Devine SM, Jimenez Jimenez AM. Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis after mismatched unrelated donor peripheral blood stem cell transplantation. J Clin Oncol. 2025;43(25):2772–81. https://doi.org/10.1200/JCO-25-00856 DOI: https://doi.org/10.1200/JCO-25-00856
51. Sanz J, Labopin M, Choi G, Kulagin A, Peccatori J, Vydra J, Reményi P, Versluis J, Rovira M, Blaise D, Labussière-Wallet H, Montoro J, Sica S, Meijer E, Itälä-Remes M, Schaap N, Bulabois CE, Piemontese S, Mohty M, Ciceri F. Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT. Blood. 2024;143(24):2534–43. https://doi.org/10.1182/blood.2023023697 DOI: https://doi.org/10.1182/blood.2023023697
52. Sanz J, Ferhat AT, Kulagin A, Kröger N, Rovira M, Lazzari L, Arat M, Montoro J, Versluis J, Reményi P, Sica S, Blaise D, Saif MA, Vydra J, Fagioli F, Nur E, Giebel S, Peric Z, Brissot E, Nagler A, Piemontese S, Mohty M, Ciceri F. Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2025;111(3):981–9. https://doi.org/10.3324/haematol.2025.287750 DOI: https://doi.org/10.3324/haematol.2025.287750
53. Dehn J, Spellman S, Hurley CK, Shaw BE, Barker JN, Burns LJ, Confer DL, Eapen M, Fernandez-Vina M, Hartzman R, Maiers M, Marino SR, Mueller C, Perales MA, Rajalingam R, Pidala J. Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR. Blood. 2019;134(12):924–34. https://doi.org/10.1182/blood.2019001212 DOI: https://doi.org/10.1182/blood.2019001212
54. Raiola AM, Risitano A, Sacchi N, Giannoni L, Signori A, Aquino S, Bregante S, Di Grazia C, Dominietto A, Geroldi S, Ghiso A, Gualandi F, Lamparelli T, Tedone E, Van Lint MT, Varaldo R, Ibatici A, Marani C, Marotta S, Guolo F, Avenoso D, Garbarino L, Pane F, Bacigalupo A, Angelucci E. Impact of HLA disparity in haploidentical bone marrow transplantation followed by high-dose cyclophosphamide. Biol Blood Marrow Transplant. 2018;24(1):119–26. https://doi.org/10.1016/j.bbmt.2017.10.002 DOI: https://doi.org/10.1016/j.bbmt.2017.10.002
55. Kharfan-Dabaja MA, Labopin M, Ayala E, Bazarbachi A, Blaise D, Vydra J, Bramanti S, Itälä-Remes M, Schmid C, Busca A, Forcade E, Rabitsch W, Zecca M, Kröger N, Bulabois CE, Grillo G, Rambaldi A, Fanin R, Zallio F, Di Renzo N, Koc Y, Novis Y, McDonald A, Herrera Arroyo C, Sanz J, Nagler A, Ciceri F, Mohty M. Significance of degree of HLA disparity using T-cell replete peripheral blood stem cells from haploidentical donors with post transplantation cyclophosphamide in AML in first complete hematologic remission: a study of the Acute Leukemia Working Party of the EBMT. HemaSphere. 2023;7(7):e920. https://doi.org/10.1097/HS9.0000000000000920 DOI: https://doi.org/10.1097/HS9.0000000000000920
56. Ciurea SO, Al Malki MM, Kongtim P, Fuchs EJ, Luznik L, Huang XJ, Ciceri F, Locatelli F, Aversa F, Castagna L, Bacigalupo A, Martelli M, Blaise D, Ben Soussan P, Arnault Y, Handgretinger R, Roy DC, O’Donnell PV, Bashey A, Solomon S, Romee R, Gayoso J, Lazarus HM, Ballen K, Savani BN, Mohty M, Nagler A. The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation. Bone Marrow Transplant. 2020;55(1):12–24. https://doi.org/10.1038/s41409-019-0499-z DOI: https://doi.org/10.1038/s41409-019-0499-z
57. Fleischhauer K, Shaw BE, Gooley T, Malkki M, Bardy P, Bignon JD, Dubois V, Horowitz MM, Madrigal JA, Morishima Y, Oudshoorn M, Ringden O, Spellman S, Velardi A, Zino E, Petersdorf EW. Effect of T-cellepitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol. 2012;13(4):366–74. https://doi.org/10.1016/S1470-2045(12)70004-9 DOI: https://doi.org/10.1016/S1470-2045(12)70004-9
58. Arrieta-Bolaños E, Crivello P, Shaw BE, Ahn KW, Wang HL, Verneris MR, Hsu KC, Pidala J, Lee SJ, Fleischhauer K, Spellman SR. In silico prediction of nonpermissive HLA-DPB1 mismatches in unrelated HCT by functional distance. Blood Adv. 2018;2(14):1773–83. https://doi.org/10.1182/bloodadvances.2018019620 DOI: https://doi.org/10.1182/bloodadvances.2018019620
59. Mytilineos D, Tsamadou C, Neuchel C, Platzbecker U, Bunjes D, Schub N, Wagner-Drouet E, Wulf G, Kröger N, Murawski N, Einsele H, Schaefer-Eckart K, Freitag S, Casper J, Kaufmann M, Dürholt M, Hertenstein B, Klein S, Ringhoffer M, Mueller CR, Frank S, Schrezenmeier H, Fuerst D, Mytilineos J. The human leukocyte antigen-DPB1 degree of compatibility is determined by its expression level and mismatch permissiveness: a German multicenter analysis. Front Immunol. 2020;11:614976. https://doi.org/10.3389/fimmu.2020.614976 DOI: https://doi.org/10.3389/fimmu.2020.614976
60. Ruggeri A, de Wreede LC, Müller CR, Crivello P, Bonneville EF, Petersdorf EW, Socié G, Dubois V, Niittyvuopio R, Peräsaari J, Yakoub-Agha I, Cornelissen JJ, Wieten L, Gedde-Dahl T, Forcade E, Crawley CR, Marsh SGE, Gandemer V, Tholouli E, Bulabois CE, Huynh A, Choi G, Deconinck E, Itäla-Remes M, Lenhoff S, Bengtsson M, Johansson JE, van Gorkom G, Hoogenboom JD, Vago L, Rocha V, Bonini C, Chabannon C, Fleischhauer K. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation. Haematologica. 2023;108(2):645–52. https://doi.org/10.3324/haematol.2021.280055 DOI: https://doi.org/10.3324/haematol.2021.280055
61. Fuchs EJ, McCurdy SR, Solomon SR, Wang T, Herr MR, Modi D, Grunwald MR, Nishihori T, Kuxhausen M, Fingerson S, McKallor C, Bashey A, Kasamon YL, Bolon YT, Saad A, McGuirk J, Paczesny S, Gadalla SM, Marsh SGE, Shaw BE, Spellman SR, Lee SJ, Petersdorf EW. HLA informs risk predictions after haploidentical stem cell transplantation with posttransplantation cyclophosphamide. Blood. 2022; 139 (10): 1452–68. https://doi.org/10.1182/blood.2021013443 DOI: https://doi.org/10.1182/blood.2021013443
62. Yabe T, Azuma F, Kashiwase K, Matsumoto K, Orihara T, Yabe H, Kato S, Kato K, Kai S, Mori T, Morishima S, Satake M, Takanashi M, Nakajima K, Morishima Y. HLA-DPB1 mismatch induces a graft-versus-leukemia effect without severe acute GVHD after single-unit umbilical cord blood transplantation. Leukemia. 2018; 32 (1):168–75. https://doi.org/10.1038/leu.2017.202 DOI: https://doi.org/10.1038/leu.2017.202
63. Petersdorf EW, Malkki M, O’hUigin C, Carrington M, Gooley T, Haagenson MD, Horowitz MM, Spellman SR, Wang T, Stevenson P. High HLA-DP expression and graft-versus-host disease. N Engl J Med. 2015; 373(7):599–609. https://doi.org/10.1056/NEJMoa1500140 DOI: https://doi.org/10.1056/NEJMoa1500140
64. Petersdorf EW, Bengtsson M, De Santis D, Dubois V, Fleischhauer K, Gooley T, Horowitz M, Madrigal JA, Malkki M, McKallor C, Morishima Y, Oudshoorn M, Spellman SR, Villard J, Stevenson P, Carrington M. Role of HLA-DP Expression in graft-versus-host disease after unrelated donor transplantation. J Clin Oncol. 2020;38(24):2712–8. https://doi.org/10.1200/JCO.20.00265 DOI: https://doi.org/10.1200/JCO.20.00265
65. Arrieta-Bolaños E, Crivello P, He M, Wang T, Gadalla SM, Paczesny S, Marsh SGE, Lee SJ, Spellman SR, Bolon YT, Fleischhauer K. A core group of structurally similar HLA-DPB1 alleles drives permissiveness after hematopoietic cell transplantation. Blood. 2022;140(6):659–63. https://doi.org/10.1182/blood.2022015708 DOI: https://doi.org/10.1182/blood.2022015708
66. Arrieta-Bolaños E, van der Burg LLJ, Gedde-Dahl T, Robin M, Salmenniemi U, Kröger N, Yakoub-Agha I, Huynh A, Crawley C, Deconinck E, Bulabois CE, Forcade E, Tholouli E, van der Hem JGK, van Balen P, Hoogenboom JD, de Wreede LC, Malard F, Ruggeri A, Fleischhauer K. Directionality of HLA-DP permissive mismatches improves risk prediction in HCT for acute leukemia and MDS. Blood. 2024;144(16):1747–51. https://doi.org/10.1182/blood.2024024351 DOI: https://doi.org/10.1182/blood.2024024351
67. McCurdy SR, Solomon SR, Shaffer BC, He M, Bolon YT, Blouin AG, Keyzner A, Socola FA, Ibrahim U, Zou J, Safah H, Saba N, Gadalla SM, Perales MA, Paczesny S, Marsh SGE, Petersdorf EW, Wang T, Lee SJ, Fuchs EJ. Posttransplant cyclophosphamide improves survival in HLA-DPB1 mismatched unrelated donor allogeneic transplantation. Transplant Cell Ther. 2026;32(1):74.e1–e14. https://doi.org/10.1016/j.jtct.2025.09.048 DOI: https://doi.org/10.1016/j.jtct.2025.09.048
68. Nath K, Zhang MJ, Bye M, Abid MB, Benjamin C, Betts B, Bhatt NS, Arrieta Bolaños E, Bolon YT, Gadalla SM, Grunwald MR, Krem MM, Lee SJ, Marsh SGE, Martino R, Mehta PA, Milano F, Prestidge T, Saultz JN, Shaw BE, Spellman SR, Choe H, Shaffer BC. Transplant outcomes using older matched sibling donors compared with young alternative donors: a CIBMTR analysis. Blood Adv. 2025;9(14):3469–78. https://doi.org/10.1182/bloodadvances.2024014858 DOI: https://doi.org/10.1182/bloodadvances.2024014858
69. Politikos I, Davis E, Nhaissi M, Wagner JE, Brunstein CG, Cohen S, Shpall EJ, Milano F, Scaradavou A, Barker JN; American Society for Transplantation and Cellular Therapy Cord Blood Special Interest Group. Guidelines for cord blood unit selection. Biol Blood Marrow Transplant. 2020;26(12):2190–6. https://doi.org/10.1016/j.bbmt.2020.07.030 DOI: https://doi.org/10.1016/j.bbmt.2020.07.030
70. Blouin AG, Askar M. Chimerism analysis for clinicians: a review of the literature and worldwide practices. Bone Marrow Transplant. 2022;57(3):347–59. https://doi.org/10.1038/s41409-022-01579-9 DOI: https://doi.org/10.1038/s41409-022-01579-9
71. Clark A, Clouston H, Rao K, Folarin N, De la Fuente J, Hamblin A, Olavarria E, Richardson D, Talley P, Potter V, Loke J, McVeigh T, Snowden J. UK recommendations for chimerism testing and monitoring following allogeneic haematopoietic stem cell transplantation (HSCT): Best practice consensus guidelines from the British Society for Blood and Marrow Transplant and Cellular Therapies (BSBMTCT), NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group, UK Cancer Genetics Group (UKCGG) and the UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI). Br J Haematol. 2025;207(5):1802–14. https://doi.org/10.1111/bjh.70061 DOI: https://doi.org/10.1111/bjh.70061
72. Fleischhauer K, Toffalori C, Cugnata F, Hofmann JA, Orofino G, Lorentino F, Ahci-Hanci M, Lange V, Müller CR, Kunadt D, Bornhäuser M, Sanz G, Soiffer R, Waterhouse M, Giaccone L, Ali H, Nachtkamp K, Bacigalupo A, Bonifazi F, Luznik L, Facchini L, Bramanti S, Nagler A, Saccardi R, Milano F, Zallio F, Pierini A, Mohty M, Flomenberg N, Takaori-Kondo A, Vey N, Teshima T, Kröger N, Martinez Laperche C, Andreani M, Lupo Stanghellini MT, Peccatori J, Di Serio C, Kobbe G, Al Malki MM, Bruno B, Zeiser R, Lindsley RC, Sanz J, Beelen D, Stölzel F, Sauter J, Schmidt AH, Ciceri F, Vago L. Donor selection and human leukocyte antigen loss leukemia relapse after hematopoietic cell transplantation. J Clin Oncol. 2026:44:2221–32. https://doi.org/10.1200/JCO-26-00113 DOI: https://doi.org/10.1200/JCO-26-00113
73. Crucitti L, Crocchiolo R, Toffalori C, Mazzi B, Greco R, Signori A, Sizzano F, Chiesa L, Zino E, Lupo Stanghellini MT, Assanelli A, Carrabba MG, Marktel S, Marcatti M, Bordignon C, Corti C, Bernardi M, Peccatori J, Bonini C, Fleischhauer K, Ciceri F, Vago L. Incidence, risk factors and clinical outcome of leukemia relapses with loss of the mismatched HLA after partially incompatible hematopoietic stem cell transplantation. Leukemia. 2015;29(5):1143–52. https://doi.org/10.1038/leu.2014.314 DOI: https://doi.org/10.1038/leu.2014.314
74. Toffalori C, Zito L, Gambacorta V, Riba M, Oliveira G, Bucci G, Barcella M, Spinelli O, Greco R, Crucitti L, Cieri N, Noviello M, Manfredi F, Montaldo E, Ostuni R, Naldini MM, Gentner B, Waterhouse M, Zeiser R, Finke J, Hanoun M, Beelen DW, Gojo I, Luznik L, Onozawa M, Teshima T, Devillier R, Blaise D, Halkes CJM, Griffioen M, Carrabba MG, Bernardi M, Peccatori J, Barlassina C, Stupka E, Lazarevic D, Tonon G, Rambaldi A, Cittaro D, Bonini C, Fleischhauer K, Ciceri F, Vago L. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat Med. 2019;25(4):603–11. https://doi.org/10.1038/s41591-019-0400-z DOI: https://doi.org/10.1038/s41591-019-0400-z
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Alberto Cardoso Martins Lima, Danielli Cristina Muniz de Oliveira, Gisele Fabianne Rampim, Raquel Aparecida Fabreti-Oliveira, Margareth Afonso Torres
This work is licensed under a Creative Commons Attribution 4.0 International License.
