Abstract
The presence of donor-specific antibodies (DSAs) have been reported to be associated with an increased risk of primary graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its effects on the time to engraftment and long-term outcomes remain unclear. We performed a systematic review and meta-analysis of studies investigating the impact of DSAs on engraftment and long-term survival of patients undergoing allo-HSCT. We systematically searched PubMed, Embase, the Cochrane Library, and CBM. Data were analyzed using RevMan5.4. Pooled hazard ratio (HR), standard mean difference (SMD) or odds ratio (OR) and corresponding 95% confidence interval (CI) are calculated for time-to-event data, continuous data, discontinuous data respectively. 17 eligible studies were included, involving 2169 patients main receiving haploidentical SCT (haplo-SCT) or umbilical cord blood transplantation (UCBT). Meta-analysis showed that DSAs-positive patients are associated with significantly higher risk of GF(OR = 12.87, 95%CI, 6.45–25.70; P < 0.00001; OR = 4.76, 95%CI, 2.88–7.87), poorer neutrophil engraftment (HR = 2.20, 95%CI, 1.02–4.73; P = 0.04; HR = 1.83, 95%CI, 1.46–2.30; P < 0.00001), worse OS (HR = 3.19, 95%CI, 1.85–5.50; P < 0.0001; HR = 1.68, 95%CI, 1.04–2.71; P = 0.03), and inferior PFS (HR = 4.25, 95%CI, 1.59–11.40; P = 0.004; HR = 4.83, 95%CI, 1.65–14.12; P = 0.004) in haplo-SCT and UCBT, respectively.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Koh LP, Rizzieri DA, Chao NJ. Allogeneic hematopoietic stem cell transplant using mismatched/haploidentical donors. Biol Blood Marrow Transpl. 2007;13:1249–67.
Morin-Zorman S, Loiseau P, Taupin JL, Caillat-Zucman S. Donor-specific Anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7:307.
Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med. 1998;339:1177–85.
Kekre N, Antin JH. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood. 2014;124:334–43.
Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–26.
Ciurea SO, Cao K, Fernandez-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 Transpl. 2018;53:521–34.
Gladstone DE, Bettinotti MP. HLA donor-specific antibodies in allogeneic hematopoietic stem cell transplantation: challenges and opportunities. Hematol Am Soc Hematol Educ Program. 2017;2017:645–50.
Brand A, Doxiadis IN, Roelen DL. On the role of HLA antibodies in hematopoietic stem cell transplantation. Tissue Antigens. 2013;81:1–11.
Hassan S, West KA, Ward WW, Kanakry JA, Flegel WA. Rebound and overshoot of donor-specific antibodies to human leukocyte antigens (HLA) during desensitization with plasma exchanges in hematopoietic progenitor cell transplantation: a case report. Transfusion 2021;61:1980–6.
Takanashi M, Atsuta Y, Fujiwara K, Kodo H, Kai S, Sato H, et al. The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood 2010;116:2839–46.
Dahi PB, Barone J, Devlin SM, Byam C, Lubin M, Ponce DM, et al. Sustained donor engraftment in recipients of double-unit cord blood transplantation is possible despite donor-specific human leukoctye antigen antibodies. Biol Blood Marrow Transpl. 2014;20:735–9.
Muro M, Marin L, Miras M, Moya-Quiles R, Minguela A, Sanchez-Bueno F, et al. Liver recipients harbouring anti-donor preformed lymphocytotoxic antibodies exhibit a poor allograft survival at the first year after transplantation: experience of one centre. Transpl Immunol. 2005;14:91–7.
Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation 2008;86:377–83.
Bramanti S, Calafiore V, Longhi E, Mariotti J, Crespiatico L, Sarina B, et al. Donor-Specific anti-HLA antibodies in haploidentical stem cell transplantation with post-transplantation cyclophosphamide: risk of graft failure, poor graft function, and impact on outcomes. Biol Blood Marrow Transpl. 2019;25:1395–406.
Lima A, Bonfim C, Getz J, Dornelles LN, Do AG, Petterle RR, et al. 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;97:493–504.
Kharfan-Dabaja MA, Kumar A, Ayala E, Aljurf M, Nishihori T, Marsh R, et al. Standardizing definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the American society for transplantation and cellular therapy. Transpl Cell Ther. 2021;27:642–9.
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. Transpl Cell Ther. 2021;27:687.e1–687.e7.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8:16.
The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27:1785–805.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.
Ansari M, Uppugunduri CR, Ferrari-Lacraz S, Bittencourt H, Gumy-Pause F, Chalandon Y, et al. The clinical relevance of pre-formed anti-HLA and anti-MICA antibodies after cord blood transplantation in children. PLoS One. 2013;8:e72141.
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 Transpl. 2015;21:1392–8.
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.
Fuji S, Oshima K, Ohashi K, Sawa M, Saito T, Eto T, et al. 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 Transpl. 2020;55:722–8.
Srour SA, Kongtim P, Rondon G, Chen J, Petropoulos D, Ramdial J, et al. Haploidentical transplants for patients with relapse after the first allograft. Am J Hematol. 2020;95:1187–92.
Zhang R, He Y, Yang D, Jiang E, Ma Q, Pang A, et al. Combination treatment of rituximab and donor platelets infusion to reduce donor-specific anti-HLA antibodies for stem cells engraftment in haploidentical transplantation. J Clin Lab Anal. 2020;34:e23261.
Ruggeri A, Rocha V, Masson E, Labopin M, Cunha R, Absi L, et al. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Societe Francophone d’Histocompatibilite et d’Immunogenetique (SFHI) and Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) analysis. Haematologica. 2013;98:1154–60.
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 Transpl. 2012;47:508–15.
Paina OV, Pavlova IE, Ivanova NE, Alyanskiy AL, Bykova TA, Zubarovskaya LS, et al. Donor-specific anti-HLA antibodies and outcome in pediatric haploidentical hematopoietic stem cell transplantation. HLA:Immune Response Genet. 2020;9:53–8.
Pavlova I, Paina O, Alyanskiy A, Babenko E, Ivanova N, Frolova A, et al. Donor-specific anti-HLA antibodies detection by de facto crossmatch method in pediatric recipients before haploidentical hematopoetic stem cell transplantation. Cellular TherapyTranspl. 2020;95:272–422.
Zou J, Romee R, Slade M, Phelan D, Keller J, Mohanakumar T, et al. Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation. Bone Marrow Transpl. 2017;52:898–901.
Choe H, Gergis U, Hsu J, Phillips A, Shore T, Christos P, et al. Bortezomib and immune globulin have limited effects on donor-specific HLA antibodies in haploidentical cord blood stem cell transplantation: detrimental effect of persistent haploidentical donor-specific HLA antibodies. Biol Blood Marrow Transpl. 2019;25:e60–e64.
Chang YJ, Xu LP, Wang Y, Zhang XH, Chen H, Chen YH, et al. Rituximab for desensitization during HLA-mismatched stem cell transplantation in patients with a positive donor-specific anti-HLA antibody. Bone Marrow Transpl. 2020;55:1326–36.
Chang YJ, Zhao XY, Xu LP, Zhang XH, Wang Y, Han W, et al. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. J Hematol Oncol. 2015;8:84.
Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, et al. Second haploidentical stem cell transplantation for primary graft failure. Bone Marrow Transpl. 2021;56:1291–6.
Funding
Prof. Xu was supported by the Project from Southwest Hospital (2022DZXDX004). Prof Chen was supported by the Logistics Project (AWS17J007).
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YRH and SNX designed the project and protocols. YRH and CXL conducted the searches, extracted the data, and excluded duplicates. GXW, XTH, ZH and YQD, screened studies, conducted quality appraisal and extracted data. YRH performed the meta-analysis, accessing the raw data. YRH and CXL drafted the manuscript. JPC, QL and SNX critically revised the manuscript.
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Huang, Y., Luo, C., Wu, G. et al. 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 58, 544–551 (2023). https://doi.org/10.1038/s41409-023-01932-6
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DOI: https://doi.org/10.1038/s41409-023-01932-6
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