The online version of this article (doi:10.1186/s13045-017-0398-y) contains supplementary material, which is available to authorized users.
Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients.
We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled.
Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9–20) and 11 (range, 8–19) days, with a cumulative incidence of 97.8 and 97.1% (P = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II–IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P < 0.001), grades III–IV aGVHD (10.1 vs. 1.5%, P = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% (P = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% (P = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type.
Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.
Additional file 1: Table S1. Univariate analysis of factors associated with survival outcomes. Table S2. Univariate analysis of factors associated with II–IV aGVHD and III–IV aGVHD. Figure S1a. The cumulative incidence of 28-day neutrophil engraftment:HID97.75 ± 0.03%, MRD97.10 ± 0.05% (P = 0.528). Figure S1b. The cumulative incidence of platelet engraftment: HID96.63 ± 0.05%, MRD 95.65 ± 0.08% (P = 0.989). Figure S2a. The cumulative incidence of II–IV aGVHD: HID 30.34 ± 0.24%, MRD1.45 ± 0.02% (P < 0.001). Figure S2b. The cumulative incidence of III–IV aGVHD: HID10.11 ± 0.10%, MRD1.45 ± 0.02% (P = 0.026). Figure S3a. The cumulative incidence of cGVHD (P < 0.001). Figure S3b. The cumulative incidence of extensive cGVHD (P = 0.426). (DOCX 42 kb)13045_2017_398_MOESM1_ESM.docx
Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Fuhrer M. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2007;92:11–8. CrossRefPubMed
Saracco P, Quarello P, Iori AP, Zecca M, Longoni D, Svahn J, Varotto S, Del Vecchio GC, Dufour C, Ramenghi U, et al. Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol. 2008;140:197–205. CrossRefPubMed
Chen J, Lee V, Luo CJ, Chiang AK, Hongeng S, Tan PL, Tan AM, Sanpakit K, Li CF, Lee AC, et al. Allogeneic stem cell transplantation for children with acquired severe aplastic anaemia: a retrospective study by the Viva-Asia Blood and Marrow Transplantation Group. Br J Haematol. 2013;162:383–91. CrossRefPubMed
Dufour C, Veys P, Carraro E, Bhatnagar N, Pillon M, Wynn R, Gibson B, Vora AJ, Steward CG, Ewins AM, et al. Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT. Br J Haematol. 2015;171:585–94. CrossRefPubMed
Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer. 2013;119:978–85. CrossRefPubMed
Gao L, Zhang C, Gao L, Liu Y, Su Y, Wang S, Li B, Yang T, Yuan Z, Zhang X. Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China. J Hematol Oncol. 2015;8:90. CrossRefPubMedPubMedCentral
Camitta BM, Thomas ED, Nathan DG, Santos G, Gordon-Smith EC, Gale RP, Rappeport JM, Storb R. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood. 1976;48:63–70. PubMed
Lai YR, Chen YH, Hu DM, Jiang M, Liu QF, Liu L, Hou J, Schwarzenberger P, Li QC, Zhang ZM, et al. Multicenter phase II study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG). J Hematol Oncol. 2014;7:59. CrossRefPubMedPubMedCentral
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8. PubMed
Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, Chen H, Liu DH, Gao ZY, Chen YH, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–73. CrossRefPubMed
Champlin RE, Horowitz MM, van Bekkum DW, Camitta BM, Elfenbein GE, Gale RP, Gluckman E, Good RA, Rimm AA, Rozman C, et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood. 1989;73:606–13. PubMed
Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA, Thomas ED. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol. 1988;6:1562–8. PubMed
Kahl C, Leisenring W, Deeg HJ, Chauncey TR, Flowers ME, Martin PJ, Sanders JE, Storb R. Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br J Haematol. 2005;130:747–51. CrossRefPubMed
Kiem HP, McDonald GB, Myerson D, Spurgeon CL, Deeg HJ, Sanders JE, Doney K, Appelbaum FR, Sullivan KM, Witherspoon RP, Storb R. Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors. Biol Blood Marrow Transplant. 1996;2:93–9. PubMed
Eapen M, Ramsay NK, Mertens AC, Robison LL, DeFor T, Davies SM. Late outcomes after bone marrow transplant for aplastic anaemia. Br J Haematol. 2000;111:754–60. PubMed
McCann SR, Bacigalupo A, Gluckman E, Hinterberger W, Hows J, Ljungman P, Marin P, Nissen C, van’t Veer Kerthof E, Raghavachar A, et al. Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. Bone Marrow Transplant. 1994;13:233–7. PubMed
Gao L, Li Y, Zhang Y, Chen X, Gao L, Zhang C, Liu Y, Kong P, Wang Q, Su Y, et al. Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy. Bone Marrow Transplant. 2014;49:519–24. CrossRefPubMed
Dulley FL, Vigorito AC, Aranha FJ, Sturaro D, Ruiz MA, Saboya R, Macedo MC, Da Silva RL, Chamone DA, Mehta J, et al. Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection. Bone Marrow Transplant. 2004;33:9–13. CrossRefPubMed
Vo PT, Pantin J, Ramos C, Cook L, Cho E, Kurlander R, Khuu H, Barrett J, Leitman S, Childs RW. Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor. J Hematol Oncol. 2015;8:78. CrossRefPubMedPubMedCentral
Xu LP, Liu KY, Liu DH, Chen H, Han W, Chen YH, Wang Y, Huang XJ. The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis. Bone Marrow Transplant. 2010;45:985–92. CrossRefPubMed
Gluckman E, Horowitz MM, Champlin RE, Hows JM, Bacigalupo A, Biggs JC, Camitta BM, Gale RP, Gordon-Smith EC, Marmont AM, et al. Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome. Blood. 1992;79:269–75. PubMed
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