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01-08-2020 | Graft-Versus-Host Disease | Original Article

Outcomes of allogeneic haematopoietic stem cell transplantation for patients with severe aplastic anaemia using the porcine antilymphocyte globulin-containing conditioning regimen

Authors: Lin Li, Yun Li, Li Lin, Jin Yin, Jinhuan Xu, Jia Wei, Yicheng Zhang

Published in: Annals of Hematology | Issue 8/2020

Abstract

Antithymocyte globulin (ATG) is widely used for allogeneic haematopoietic stem cell transplantation (allo-HSCT) in severe aplastic anaemia (SAA). Only rabbit-ATG (r-ATG) and porcine-antilymphocyte globulin (p-ALG) are available in China, but the p-ALG-containing conditioning regimen for allo-HSCT in SAA has seldom been reported. In this study, we retrospectively evaluated the outcomes of 41 SAA patients receiving allo-HSCT with a p-ALG-containing conditioning regimen in our transplantation centre. All patients engrafted, and no death during conditioning was observed. The actuarial 3-year overall survival (OS) rates were 95.1 ± 3.4%. The actuarial 3-year disease-free survival (DFS) rates were 85.0 ± 5.7%. Acute graft-versus-host disease (aGVHD) predicted inferior OS (p < 0.05). The interval from diagnosis to transplantation for more than 100 days predicted an inferior DFS rate (p < 0.05) and a higher graft rejection/poor graft function (GR/PGF) rate (p < 0.01). In conclusion, the p-ALG-containing regimen showed satisfactory effects and safety in allo-HSCT for SAA patients. P-ALG could be a potential alternative preparation for r-ATG in SAA allo-HSCT.

Camitta BM, Thomas ED (1978) Severe aplastic anaemia: a prospective study of the effect of androgens or transplantation on haematological recovery and survival. Clinics in haematology 7:587–595PubMed

Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E et al (2007) Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 110:1397–1400PubMedPubMedCentral

Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A, Schrezenmeier H, Passweg J, Fuhrer M, on the behalf of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation (SAA-WP, BMT) (2007) 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 92:11–18PubMed

Socie G, Henry-Amar M, Bacigalupo A, Hows J, Tichelli A, Ljungman P, McCann SR, Frickhofen N, van't Veer-Korthof E, Gluckman E (1993) Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. N Engl J Med 329:1152–1157PubMed

Vo PT, Pantin J, Ramos C, Cook L, Cho E, Kurlander R, Khuu H, Barrett J, Leitman S, Childs RW (2015) 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 8:78PubMedPubMedCentral

Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS (2011) Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 365:430–438PubMedPubMedCentral

Zander AR, Zabelina T, Kroger N, Renges H, Kruger W, Loliger C et al (1999) Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow. Bone Marrow Transplant 23:889–893PubMed

Kroger N, Zabelina T, Kruger W, Renges H, Stute N, Durken M et al (2001) Anti-thymocyte-globulin as part of the preparative regimen prevents graft failure and severe graft versus host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors. Ann Hematol 80:209–215PubMed

Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, van Lint MT, Bosi A, for Gruppo Italiano Trapianti Midollo Osseo (GITMO) (2001) Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 98:2942–2947PubMed

10.

Bacigalupo A, Oneto R, Lamparelli T, Gualandi F, Bregante S, Raiola AM, di Grazia C, Dominietto A, Romagnani C, Bruno B, van Lint M, Frassoni F (2001) Pre-emptive therapy of acute graft-versus-host disease: a pilot study with antithymocyte globulin (ATG). Bone Marrow Transplant 28:1093–1096PubMed

11.

Remberger M, Storer B, Ringden O, Anasetti C (2002) Association between pretransplant thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors. Bone Marrow Transplant 29:391–397PubMed

12.

Bonifazi F, Bandini G, Rondelli D, Falcioni S, Stanzani M, Bontadini A, Tazzari PL, Arpinati M, Giannini B, Conte R, Baccarani M (2003) Reduced incidence of GVHD without increase in relapse with low-dose rabbit ATG in the preparative regimen for unrelated bone marrow transplants in CML. Bone Marrow Transplant 32:237–242PubMed

13.

Finke J, Schmoor C, Lang H, Potthoff K, Bertz H (2003) Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 21:506–513

14.

Wei J, Huang Z, Guo J, Zhang Y, Wang C, Zhu X, Zhang Y (2015) Porcine antilymphocyte globulin (p-ALG) plus cyclosporine A (CsA) treatment in acquired severe aplastic anemia: a retrospective multicenter analysis. Ann Hematol 94:955–962PubMed

15.

Chen M, Liu C, Zhuang J, Zou N, Xu Y, Zhang W, Li J, Duan M, Zhu T, Cai H, Cao X, Wang S, Zhou D, Han B (2016) Long-term follow-up study of porcine anti-human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia. Eur J Haematol 96:291–296PubMed

16.

Ma X, Wang J, Zhang W, Cao X, Chen Y, He A, Liu J, Yang N, Wang J, Yang Y, Xu Y (2016) Comparison of porcine anti-human lymphocyte globulin and rabbit anti-human thymocyte globulin in the treatment of severe aplastic anemia: a retrospective single-center study. Eur J Haematol 96:260–268PubMed

17.

Kojima S (2017) Why is the incidence of aplastic anemia higher in Asia? Expert Rev Hematol 10:277–279PubMed

18.

Bacigalupo A, Passweg J (2009) Diagnosis and treatment of acquired aplastic anemia. Hematol Oncol Clin North Am 23:159–170PubMed

19.

Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, Chanswangphuwana C, Efebera YA, Holler E, Litzow M, Ordemann R, Qayed M, Renteria AS, Reshef R, Wölfl M, Chen YB, Goldstein S, Jagasia M, Locatelli F, Mielke S, Porter D, Schechter T, Shekhovtsova Z, Ferrara JLM, Levine JE (2016) International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai acute GVHD international consortium. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22:4–10

20.

Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW et al. (2015) National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation; 21: 389–401.e381

21.

Lai YR, Chen YH, Hu DM, Jiang M, Liu QF, Liu L, Hou J, Schwarzenberger P, Li QC, Zhang ZM, Liu KY, Huang XJ (2014) 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 7:59PubMedPubMedCentral

22.

Champlin RE, Horowitz MM, van Bekkum DW, Camitta BM, Elfenbein GE, Gale RP, Gluckman E, Good RA, Rimm AA, Rozman C (1989) Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood 73:606–613PubMed

23.

Storb R, Weiden PL, Sullivan KM, Appelbaum FR, Beatty P, Buckner CD, Clift RA, Doney KC, Hansen J, Martin PJ (1987) Second marrow transplants in patients with aplastic anemia rejecting the first graft: use of a conditioning regimen including cyclophosphamide and antithymocyte globulin. Blood 70:116–121PubMed

24.

Gale RP (2016) Early and late graft-failure after transplants. Bone Marrow Transplant 51:182–183PubMed

25.

Rodriguez V, Khan SP (2002) Late graft rejection following allogeneic bone marrow transplantation in aplastic anemia. Transplant Proc 34:1307–1309PubMed

26.

Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C et al (2006) Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica 91:935–940PubMed

27.

Askaa B, Fischer-Nielsen A, Vindelov L, Haastrup EK, Sengelov H (2014) Treatment of poor graft function after allogeneic hematopoietic cell transplantation with a booster of CD34-selected cells infused without conditioning. Bone Marrow Transplant 49:720–721PubMed

28.

Konopacki J, Porcher R, Robin M, Bieri S, Cayuela JM, Larghero J, Xhaard A, Andreoli AL, Dhedin N, Petropoulou A, Rodriguez-Otero P, Ribaud P, Moins-Teisserenc H, Carmagnat M, Toubert A, Chalandon Y, Socie G, Peffault de Latour R (2012) Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning. Haematologica 97:710–716PubMedPubMedCentral

29.

De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 46:1813–1821

30.

Dezern AE, Brodsky RA (2011) Clinical management of aplastic anemia. Expert Rev Hematol 4:221–230PubMedPubMedCentral

31.

Kang HJ, Shin HY, Choi HS, Ahn HS (2004) Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. Bone Marrow Transplant 34:939–943PubMed

32.

Group RBCDA (2017) Chinese expert consensus on the diagnosis and treatment of aplastic anemia (2017). Zhonghua xue ye xue za zhi =. Zhonghua xueyexue zazhi 38:1–5

33.

Feng X, Scheinberg P, Biancotto A, Rios O, Donaldson S, Wu C, Zheng H, Sato K, Townsley DM, McCoy JP, Young NS (2014) In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. Haematologica 99:1433–1440PubMedPubMedCentral

34.

Chen X, Wei J, Huang Y, He Y, Yang D, Zhang R, Jiang E, Ma Q, Zhai W, Yao J, Zhang G, Feng S, Han M (2018) Effect of antithymocyte globulin source on outcomes of HLA-matched sibling allogeneic hematopoietic stem cell transplantation for patients with severe aplastic anemia. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 24:86–90

35.

Kumar R, Kimura F, Ahn KW, Hu ZH, Kuwatsuka Y, Klein JP, Pasquini M, Miyamura K, Kato K, Yoshimi A, Inamoto Y, Ichinohe T, Wood WA Jr, Wirk B, Seftel M, Rowlings P, Marks DI, Schultz KR, Gupta V, Dedeken L, George B, Cahn JY, Szer J, Lee JW, Ho AYL, Fasth A, Hahn T, Khera N, Dalal J, Bonfim C, Aljurf M, Atsuta Y, Saber W (2016) Comparing outcomes with bone marrow or peripheral blood stem cells as graft source for matched sibling transplants in severe aplastic anemia across different economic regions. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22:932–940

36.

Chen M, Liu C, Qiao X, Zhou D, Zhuang J, Han B (2018) Comparative study of porcine anti-human lymphocyte immunoglobulin and rabbit anti-human thymocyte immunoglobulin as a first-line treatment of acquired severe aplastic anemia. Leuk Res 65:55–60PubMed

37.

Bing H, Siyi Y, Wei Z, Jian L, Minghui D, Li J, Shujie W, Daobin Z, Nong Z, Tienan Z, Ying X, Yongqiang Z, Ti S (2010) The use of anti-human T lymphocyte porcine immunoglobulin and cyclosporine a to treat patients with acquired severe aplastic anemia. Acta Haematol 124:245–250PubMed

38.

Maury S, Bacigalupo A, Anderlini P, Aljurf M, Marsh J, Socie G, Oneto R, Passweg JR, on behalf of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT-SAAWP) (2009) Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen. Haematologica 94:1312–1315PubMedPubMedCentral

39.

Bacigalupo A, Oneto R, Bruno B, Socie G, Passweg J, Locasciulli A et al. Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation Acta haematologica 2000; 103: 19–25

40.

Rondon G, Saliba RM, Khouri I, Giralt S, Chan K, Jabbour E et al (2008) Long-term follow-up of patients who experienced graft failure postallogeneic progenitor cell transplantation. Results of a single institution analysis. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 14:859–866

41.

Ozdemir ZN, Civriz BS (2018) Graft failure after allogeneic hematopoietic stem cell transplantation. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 57:163–167

42.

Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J, Li Z, Chen J, Zhu X, Mao X, Wu D, Tang X (2018) Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol 11:103PubMedPubMedCentral

43.

Castagnola E, Bagnasco F, Bandettini R, Caviglia I, Morreale G, Lanino E, Giardino S, Moroni C, Haupt R, Faraci M (2014) Role of acute graft-versus-host disease in the risk of bacteremia and invasive fungal disease after allogeneic hemopoietic stem cell transplantation in children. Results from a single-center observational study. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20:1068–1073

Title: Outcomes of allogeneic haematopoietic stem cell transplantation for patients with severe aplastic anaemia using the porcine antilymphocyte globulin-containing conditioning regimen
Authors: Lin Li
Yun Li
Li Lin
Jin Yin
Jinhuan Xu
Jia Wei
Yicheng Zhang
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Graft-Versus-Host Disease
Graft-Versus-Host Disease
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: Annals of Hematology / Issue 8/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04111-5

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