Abstract
Data regarding the optimal approach for second allogeneic hematopoietic stem cell transplantation (HSCT) after graft failure (GF) in acquired severe aplastic anemia (SAA) are still limited and heterogeneous. We examined 24 patients who underwent second HLA-matched sibling donor (MSD) peripheral blood HSCT for GF. The reconditioning regimen (TNI-750/ATG) consisted of a single dose of total nodal irradiation (TNI, 750 cGy) and antithymocyte globulin (ATG; Thymoglobulin®, 1.25 mg/kg/day for 3 days). All but one patient achieved successful engraftment of neutrophils (median 12 days, range 5–21) and platelets (median 15 days, range 9–316). Two patients with subsequent secondary GF achieved successful engraftment after a third HSCT from the same MSD. After a median follow-up of 57.4 months (range, 11.2–155.2), the 5-year overall survival and failure-free survival were 95.7% (95% confidence interval [CI] 87.7–100%) and 87.5% (95% CI 75.2–100%), respectively. One patient developed grade II acute graft-versus-host disease (GVHD), and the 2-year cumulative incidence of chronic GVHD was 23.5% (95% CI 8.1–43.5%). This study demonstrated successful outcomes following a second MSD HSCT in SAA after GF, and the results suggest TNI-750/ATG is a feasible reconditioning option. Future studies with larger cohorts will validate our results.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Stucki A, Leisenring W, Sandmaier BM, Sanders J, Anasetti C, Storb R. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Blood. 1998;92:2742–9.
Bacigalupo A, Socie G, Hamladji RM, Aljurf M, Maschan A, Kyrcz-Krzemien S, et al. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica. 2015;100:696–702.
Horowitz MM. Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol. 2000;37:30–42.
Shin SH, Jeon YW, Yoon JH, Yahng SA, Lee SE, Cho BS, et al. Comparable outcomes between younger (40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning. Bone Marrow Transplant. 2016;51:1456–63.
Champlin RE, Perez WS, Passweg JR, Klein JP, Camitta BM, Gluckman E, et al. Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens. Blood. 2007;109:4582–5.
Champlin RE, Horowitz MM, van Bekkum DW, Camitta BM, Elfenbein GE, Gale RP, et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood. 1989;73:606–13.
Weisdorf DJ, Verfaillie CM, Davies SM, Filipovich AH, Wagner JE Jr., Miller JS, et al. Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony-stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte-CSF. Blood. 1995;85:3452–6.
Hogan WJ, Little MT, Zellmer E, Friedetzky A, Diaconescu R, Gisburne S, et al. Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates. Biol Blood Marrow Transplant. 2003;9:489–95.
Min CK, Kim DW, Lee JW, Min WS, Kim CC. Additional stem cell therapy for graft failure after allogeneic bone marrow transplantation. Acta Haematol. 2000;104:185–92.
Wolff SN. Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation. Bone Marrow Transplant. 2002;29:545–52.
Grandage VL, Cornish JM, Pamphilon DH, Potter MN, Steward CG, Oakhill A, et al. Second allogeneic bone marrow transplants from unrelated donors for graft failure following initial unrelated donor bone marrow transplantation. Bone Marrow Transplant. 1998;21:687–90.
Lee YH, Kim JY, Choi BO, Ryu MR, Chung SM. Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia. Radiat Oncol J. 2012;30:165–72.
Lee JW, Cho BS, Lee SE, Eom KS, Kim YJ, Kim HJ, et al. The outcome of unrelated hematopoietic stem cell transplants with total body irradiation (800 cGy) and cyclophosphamide (120 mg/kg) in adult patients with acquired severe aplastic anemia. Biol Blood Marrow Transplant. 2011;17:101–8.
Rothberg PG, Gamis AS, Baker D. Use of DNA polymorphisms to monitor engraftment after allogeneic bone marrow transplantation. Clin Lab Med. 1997;17:109–18.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. 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. Biol Blood Marrow Transplant. 2005;11:945–56.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–2919.
Cho BS, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, et al. HLA-matched sibling transplantation with BM and CD34(+)-purified PBSCs in adult patients with high-risk severe aplastic anemia to overcome graft rejection without an increase in GVHD. Bone Marrow Transplant. 2010;45:1497–501.
Cesaro S, Peffault de Latour R, Tridello G, Pillon M, Carlson K, Fagioli F, et al. Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2015;171:606–14.
Horan JT, Carreras J, Tarima S, Camitta BM, Gale RP, Hale GA, et al. Risk factors affecting outcome of second HLA-matched sibling donor transplantations for graft failure in severe acquired aplastic anemia. Biol Blood Marrow Transplant. 2009;15:626–31.
Ramsay NK, Kim TH, McGlave P, Goldman A, Nesbit ME Jr., Krivit W, et al. Total lymphoid irradiation and cyclophosphamide conditioning prior to bone marrow transplantation for patients with severe aplastic anemia. Blood. 1983;62:622–6.
Muller AM, Poyser J, Kupper NJ, Burnett C, Ko RM, Kohrt HE, et al. Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment. Blood. 2014;123:2882–92.
Inamoto Y, Suzuki R, Kuwatsuka Y, Yasuda T, Takahashi T, Tsujimura A, et al. Long-term outcome after bone marrow transplantation for aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning regimen. Biol Blood Marrow Transplant. 2008;14:43–9.
Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009;114:1099–109.
Acknowledgements
We acknowledge all members at the Catholic Blood and Marrow Transplantation Center of Seoul St. Mary’s Hospital, Seoul, Korea, particularly the house staff and nurses, for excellent care of the patients.
Funding
This study was supported in part by Green Cross Corp, Korea.
Author information
Authors and Affiliations
Contributions
SAY contributed to study design, patient management, and participated in data analysis and manuscript writing. JWL conceived of the idea and planned the clinical trial project, cared for patients, analyzed clinical data, and wrote the manuscript. SAY, SSP, YWJ, JHY, SHS, and SEL contributed to patient care and results analysis. KSE, YJK, SL, CKM, HJK, SGC, DWK, and WSM all took part in results analysis and reviewed the paper. All authors approved the final version of the manuscript. The corresponding author (JWL) had final responsibility for the decision to submit for publication.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Yahng, SA., Park, SS., Jeon, YW. et al. Successful outcomes of second hematopoietic stem cell transplantation with total nodal irradiation and ATG conditioning for graft failure in adult patients with severe aplastic anemia. Bone Marrow Transplant 53, 1270–1277 (2018). https://doi.org/10.1038/s41409-018-0154-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-018-0154-0
This article is cited by
-
Successful outcomes of second hematopoietic stem cell transplantation for graft failure in pediatric patients with severe aplastic anemia
Scientific Reports (2022)
-
Salvage HLA-haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for graft failure in non-malignant disorders
Bone Marrow Transplantation (2021)
-
Excellent outcomes of hematopoietic stem cell transplantation with total nodal irradiation and antithymocyte globulin conditioning in severe aplastic anemia with advanced age and/or severe comorbidity
Bone Marrow Transplantation (2020)