Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party

被引：175

作者：

Marsh, Judith C. ^{[1
]}

Bacigalupo, Andrea ^{[2
]}

Schrezenmeier, Hubert ^{[3
,4
]}

Tichelli, Andre ^{[5
]}

Risitano, Antonio M. ^{[6
]}

Passweg, Jakob R. ^{[5
]}

Killick, Sally B. ^{[7
]}

Warren, Alan J. ^{[8
]}

Foukaneli, Theodora ^{[8
]}

Aljurf, Mahmoud ^{[9
]}

Al-Zahrani, H. A. ^{[9
]}

Schafhausen, Philip ^{[10
]}

Roth, Alexander ^{[11
]}

Franzke, Anke ^{[12
]}

Brummendorf, Tim H. ^{[13
]}

Dufour, Carlo ^{[14
]}

Oneto, Rosi ^{[2
]}

Sedgwick, Philip ^{[15
]}

Barrois, Alain ^{[16
]}

Kordasti, Shahram ^{[1
]}

Elebute, Modupe O. ^{[1
]}

Mufti, Ghulam J. ^{[1
]}

Socie, Gerard ^{[17
,18
]}

机构：

[1] Kings Coll London, Dept Haematol Med, Univ London Kings Coll Hosp, London SE5 9RS, England

[2] Azienda Osped Univ San Martino, Dept Hematol 2, Genoa, Italy

[3] German Red Cross Blood Transfus Serv, Inst Clin Transfus Med & Immunogenet, Ulm, Germany

[4] Univ Ulm, Ulm, Germany

[5] Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland

[6] Univ Naples Federico II, Dept Biochem & Med Biotechnol, Naples, Italy

[7] Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England

[8] Univ Cambridge, Dept Haematol, Cambridge, England

[9] King Faisal Specialist Hosp & Res Ctr, Adult Hematol HSCT Oncol Ctr, Riyadh 11211, Saudi Arabia

[10] Univ Canc Ctr Hamburg, Dept Oncol & Hematol, Hamburg, Germany

[11] Univ Hosp Essen, W German Canc Ctr, Dept Hematol, Essen, Germany

[12] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, D-3000 Hannover, Germany

[13] Rhein Westfal TH Aachen, Univ Hosp, Dept Hematol & Oncol, D-52062 Aachen, Germany

[14] G Gaslini Childrens Res Hosp, Hematol Unit, Genoa, Italy

[15] Univ London, Ctr Med & Healthcare Educ, London, England

[16] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, European Blood & Marrow Transplant Clin Trials Of, Leiden, Netherlands

[17] Hosp St Louis, Paris, France

[18] Univ Paris 07, Paris, France

来源：

BLOOD | 2012年 / 119卷 / 23期

关键词：

STEM-CELL TRANSPLANTATION; ALEMTUZUMAB PLUS CYCLOSPORINE; ANTI-THYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; ALTERNATIVE DONOR; STIMULATING FACTOR; FOLLOW-UP; T-CELLS; HORSE; CYCLOPHOSPHAMIDE;

D O I：

10.1182/blood-2012-02-407684

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age- and disease severity-matched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P = .009). Transplant-free survival was 52% for rATG and 76% for hATG (P = .002). On multivariate analysis, rATG (hazard ratio = 3.9, P = .003) and age more than 37 years (hazard ratio = 4.7, P = .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848. (Blood. 2012;119(23):5391-5396)

引用

页码：5391 / 5396

页数：6

共 39 条

[1] Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia [J].

Afable, Manuel G., II ;

Shaik, Mohammed ;

Sugimoto, Yuka ;

Elson, Paul ;

Clemente, Michael ;

Makishima, Hideki ;

Sekeres, Mikkael A. ;

Lichtin, Alan ;

Advani, Anjali ;

Kalaycio, Matt ;

Tiu, Ramon V. ;

O'Keefe, Christine L. ;

Maciejewski, Jaroslaw P. .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2011, 96 (09) :1269-1275

[2] Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study [J].

Atta, Elias Hallack ;

Saldanha, Danielle ;

Dias, Peixoto ;

Marra, Vera Lucia Neves ;

de Azevedo, Alexandre Mello .

ANNALS OF HEMATOLOGY, 2010, 89 (09) :851-859

[3] Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party [J].

Bacigalupo, Andrea ;

Socie', Gerard ;

Lanino, Edoardo ;

Prete, Arcangelo ;

Locatelli, Franco ;

Locasciulli, Anna ;

Cesaro, Simone ;

Shimoni, Avichai ;

Marsh, Judith ;

Brune, Mats ;

Van Lint, Maria Teresa ;

Oneto, Rosi ;

Passweg, Jacob .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (06) :976-982

[4] A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients [J].

Brennan, DC ;

Flavin, K ;

Lowell, JA ;

Howard, TK ;

Shenoy, S ;

Burgess, S ;

Dolan, S ;

Kano, JM ;

Mahon, M ;

Schnitzler, MA ;

Woodward, R ;

Irish, W ;

Singer, GG .

TRANSPLANTATION, 1999, 67 (07) :1011-1018

[5] High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up [J].

Brodsky, Robert A. ;

Chen, Allen R. ;

Dorr, Donna ;

Fuchs, Ephraim J. ;

Huff, Carol Ann ;

Luznik, Leo ;

Smith, B. Douglas ;

Matsui, William H. ;

Goodman, Steven N. ;

Ambinder, Richard F. ;

Jones, Richard J. .

BLOOD, 2010, 115 (11) :2136-2141

[6] PD-1+ T Cell Subsets in Follicular Lymphoma Tumor Microenvironment and Their Implications for Prognosis and Therapy [J].

Chu, Fuliang ;

Ma, Wencai ;

Yamazaki, Tomohide ;

Foglietta, Myriam ;

Nattama, Durga ;

Rawal, Seema ;

Wang, Zhiqiang ;

Gao, Yanli ;

Orozco, Natalia M. ;

Vence, Luis ;

Radvanyi, Laszlo ;

Dong, Chen ;

Davis, Richard Eric ;

Neelapu, Sattva S. .

BLOOD, 2011, 118 (21) :1137-1138

[7] Th17 immune responses contribute to the pathophysiology of aplastic anemia [J].

de Latour, Regis Peffault ;

Visconte, Valeria ;

Takaku, Tomoiku ;

Wu, Colin ;

Erie, Andrew J. ;

Sarcon, Annahita K. ;

Desierto, Marie J. ;

Scheinberg, Phillip ;

Keyvanfar, Keyvan ;

Nunez, Olga ;

Chen, Jichun ;

Young, Neal S. .

BLOOD, 2010, 116 (20) :4175-4184

[8] Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy [J].

Di Bona, E ;

Rodeghiero, E ;

Bruno, B ;

Gabbas, A ;

Foa, P ;

Locasciulli, A ;

Rosanelli, C ;

Camba, L ;

Saracco, P ;

Lippi, A ;

Iori, AP ;

Porta, F ;

De Rossi, V ;

Comotti, B ;

Iacopino, P ;

Dufour, C ;

Bacigalupo, A .

BRITISH JOURNAL OF HAEMATOLOGY, 1999, 107 (02) :330-334

[9] Rabbit ATG for aplastic anaemia treatment: a backward step? [J].

Dufour, Carlo ;

Bacigalupo, Andrea ;

Oneto, Rosi ;

Socie, Gerard ;

Tichelli, Andre ;

Passweg, Jakob R. ;

Risitano, Antonio M. ;

Schrezenmeier, Hubert ;

Locasciulli, Anna ;

Aljurf, Mohammed ;

Marsh, Judith C. W. .

LANCET, 2011, 378 (9806) :1831-1833

[10]

European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party, COMPL TREATM ALG SAA

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