Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia

被引：0

作者：

Zhang, Lining ^{[1
,2
,3
]}

Li, Jianping ^{[1
,2
,3
]}

Liang, Weiru ^{[1
,2
,3
]}

Zhang, Xiaoyu ^{[1
,2
,3
]}

Chen, Shulian ^{[1
,2
,3
]}

Shi, Yuanyuan ^{[1
,2
,3
]}

Hao, Mengze ^{[1
,2
,3
]}

Zhao, Xiaoli ^{[1
,2
,3
]}

Gong, Ming ^{[1
,2
,3
]}

Wei, Jialin ^{[1
,2
,3
]}

He, Yi ^{[1
,2
,3
]}

Jiang, Erlie ^{[1
,2
,3
]}

Han, Mingzhe ^{[1
,2
,3
]}

Zhang, Fengkui ^{[1
,2
,3
]}

Feng, Sizhou ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Expt Hematol, Inst Hematol, Natl Clin Res Ctr Blood Dis,Haihe Lab Cell Ecosys, Tianjin, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Blood Dis Hosp, Tianjin, Peoples R China

[3] Tianjin Inst Hlth Sci, Tianjin, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2024年 / 15卷

关键词：

severe aplastic anemia; relapse; refractory; hematopoietic stem cell transplantation; immunosuppressive therapy; HIGH-DOSE CYCLOPHOSPHAMIDE; RABBIT ANTITHYMOCYTE GLOBULIN; BONE-MARROW-TRANSPLANTATION; EUROPEAN GROUP; ALTERNATIVE DONOR; SALVAGE THERAPY; GRAFT FAILURE; BLOOD; HORSE; CYCLOSPORINE;

D O I：

10.3389/fimmu.2024.1425076

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% +/- 0.7% and 13.9% +/- 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% +/- 0.7%, with moderate to severe cGVHD at 14.9% +/- 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% +/- 6.8% vs. 80.0% +/- 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% +/- 6.8% vs. 56.6% +/- 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% +/- 17.7%, p = 0.004) and FFS (100% vs. 50.0% +/- 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age <= 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

引用

页数：10

共 48 条

[11] Immunosuppressive therapy versus alternative donor hematopoietic stem cell transplantation for children with severe aplastic anemia who lack an HLA-matched familial donor [J].

Choi, Y. B. ;

Yi, E. S. ;

Lee, J. W. ;

Sung, K. W. ;

Koo, H. H. ;

Yoo, K. H. .

BONE MARROW TRANSPLANTATION, 2017, 52 (01) :47-52

[12] Repeat course of rabbit antithymocyte globulin as salvage following initial therapy with rabbit antithymocyte globulin in acquired aplastic anemia [J].

Cle, Diego V. ;

Atta, Elias H. ;

Dias, Danielle S. P. ;

Lima, Carlos B. L. ;

Bonduel, Mariana ;

Sciuccati, Gabriela ;

Medeiros, Larissa A. ;

de Oliveira, Michel M. ;

Salvino, Marco A. ;

Garanito, Marlene ;

Ollala Saad, Sara T. ;

Calado, Rodrigo T. ;

Scheinberg, Phillip .

HAEMATOLOGICA, 2015, 100 (09) :E345-E347

[13] Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug [J].

Desmond, Ronan ;

Townsley, Danielle M. ;

Dumitriu, Bogdan ;

Olnes, Matthew J. ;

Scheinberg, Phillip ;

Bevans, Margaret ;

Parikh, Ankur R. ;

Broder, Kinneret ;

Calvo, Katherine R. ;

Wu, Colin O. ;

Young, Neal S. ;

Dunbar, Cynthia E. .

BLOOD, 2014, 123 (12) :1818-1825

[14] Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial [J].

DeZern, Amy E. ;

Eapen, Mary ;

Wu, Juan ;

Talano, Julie-An ;

Solh, Melhem ;

Saldana, Blachy J. Davila ;

Karanes, Chatchada ;

Horwitz, Mitchell E. ;

Mallhi, Kanwaldeep ;

Arai, Sally ;

Farhadfar, Nosha ;

Hexner, Elizabeth ;

Westervelt, Peter ;

Antin, Joseph H. ;

Deeg, H. Joachim ;

Leifer, Eric ;

Brodsky, Robert A. ;

Logan, Brent R. ;

Horowitz, Mary M. ;

Jones, Richard J. ;

Pulsipher, Michael A. .

LANCET HAEMATOLOGY, 2022, 9 (09) :E660-E669

[15] 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

Dufour, Carlo ;

Veys, Paul ;

Carraro, Elisa ;

Bhatnagar, Neha ;

Pillon, Marta ;

Wynn, Rob ;

Gibson, Brenda ;

Vora, Ajay J. ;

Steward, Colin G. ;

Ewins, Anna M. ;

Hough, Rachael E. ;

de la Fuente, Josu ;

Velangi, Mark ;

Amrolia, Persis J. ;

Skinner, Roderick ;

Bacigalupo, Andrea ;

Risitano, Antonio M. ;

Socie, Gerard ;

de Latour, Regis Peffault ;

Passweg, Jakob ;

Rovo, Alicia ;

Tichelli, Andre ;

Schrezenmeier, Hubert ;

Hochsmann, Britta ;

Bader, Peter ;

van Biezen, Anja ;

Aljurf, Mahmoud D. ;

Kulasekararaj, Austin ;

Marsh, Judith C. ;

Samarasinghe, Sujith .

BRITISH JOURNAL OF HAEMATOLOGY, 2015, 171 (04) :585-594

[17] Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation [J].

Dufour, Carlo ;

Pillon, Marta ;

Passweg, Jakob ;

Socie, Gerard ;

Bacigalupo, Andrea ;

Franceschetto, Genny ;

Carraro, Elisa ;

Oneto, Rosi ;

Risitano, Antonio Maria ;

de Latour, Regis Peffault ;

Tichelli, Andre ;

Rovo, Alicia ;

Peters, Christina ;

Hoechsmann, Britta ;

Samarasinghe, Sujith ;

Kulasekararaj, Austin G. ;

Schrezenmeier, Hubert ;

Aljurf, Mahmoud ;

Marsh, Judith .

HAEMATOLOGICA, 2014, 99 (10) :1574-1581

[18] Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection [J].

Dulley, FL ;

Vigorito, AC ;

Aranha, FJP ;

Sturaro, D ;

Ruiz, MA ;

Saboya, R ;

Macedo, MCMA ;

Da Silva, RL ;

Chamone, DAF ;

Mehta, J ;

Bacigalupo, A ;

De Souza, CA .

BONE MARROW TRANSPLANTATION, 2004, 33 (01) :9-13

[19] Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study [J].

Esteves, I. ;

Bonfim, C. ;

Pasquini, R. ;

Funke, V. ;

Pereira, N. F. ;

Rocha, V. ;

Novis, Y. ;

Arrais, C. ;

Colturato, V. ;

de Souza, M. P. ;

Torres, M. ;

Fernandes, J. F. ;

Kerbauy, F. R. ;

Ribeiro, A. A. F. ;

Santos, F. P. S. ;

Hamerschlak, N. .

BONE MARROW TRANSPLANTATION, 2015, 50 (05) :685-689

[20] National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report [J].

Filipovich, AH ;

Weisdorf, D ;

Pavletic, S ;

Socie, G ;

Wingard, JR ;

Lee, SJ ;

Martin, P ;

Chien, J ;

Przepiorka, D ;

Couriel, D ;

Cowen, EW ;

Dinndorf, P ;

Farrell, A ;

Hartzman, R ;

Henslee-Downey, J ;

Jacobsohn, D ;

McDonald, G ;

Mittleman, B ;

Rizzo, JD ;

Robinson, M ;

Schubert, M ;

Schultz, K ;

Shulman, H ;

Turner, M ;

Vogelsang, G ;

Flowers, MED .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2005, 11 (12) :945-956

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