Hematopoietic cell transplantation for aplastic anemia in adults
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
Aplastic anemia (AA) is a potentially fatal condition, especially if the disease does not respond to immunotherapy and/or progresses to severe pancytopenia. The role of hematopoietic cell transplantation (HCT) in these settings is evolving. As outcomes from HCT improve, more patients may be able to benefit from this approach.
This topic review discusses the use of HCT for adults with severe aplastic anemia (SAA). Separate topic reviews discuss the use of HCT for AA in children and adolescents and other therapies for AA in adults.
●HCT for children with AA – (See "Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents".)
●Other therapies for adults with AA – (See "Treatment of aplastic anemia in adults".)
Discussions of HCT for other bone marrow failure syndromes are also presented separately. (See "Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents" and "Hematopoietic cell transplantation for Diamond-Blackfan anemia and the myelodysplastic syndromes in children and adolescents".)
Subscribers log in hereLiterature review current through: Aug 2017. | This topic last updated: Aug 28, 2017.References
- Young NS. Aplastic anaemia. Lancet 1995; 346:228.
- Peinemann F, Grouven U, Kröger N, et al. First-line matched related donor hematopoietic stem cell transplantation compared to immunosuppressive therapy in acquired severe aplastic anemia. PLoS One 2011; 6:e18572.
- Peinemann F, Bartel C, Grouven U. First-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared with first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for acquired severe aplastic anemia. Cochrane Database Syst Rev 2013; :CD006407.
- Doney K, Leisenring W, Storb R, Appelbaum FR. Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team. Ann Intern Med 1997; 126:107.
- Passweg JR, Socié G, Hinterberger W, et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved? Blood 1997; 90:858.
- Srinivasan R, Takahashi Y, McCoy JP, et al. Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation. Br J Haematol 2006; 133:305.
- Lee JH, Choi SJ, Lee JH, et al. Non-total body irradiation containing preparative regimen in alternative donor bone marrow transplantation for severe aplastic anemia. Bone Marrow Transplant 2005; 35:755.
- Resnick IB, Aker M, Shapira MY, et al. Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen. Br J Haematol 2006; 133:649.
- George B, Mathews V, Viswabandya A, et al. Fludarabine-based reduced intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia and fungal infections. Clin Transplant 2009; 23:228.
- Maury S, Aljurf M. Management of adult patients older than 40 years refractory to at least one immunosuppressive course: HLA-identical sibling HSCT using fludarabine-based conditioning. Bone Marrow Transplant 2013; 48:196.
- George B, Mathews V, Viswabandya A, et al. Fludarabine and cyclophosphamide based reduced intensity conditioning (RIC) regimens reduce rejection and improve outcome in Indian patients undergoing allogeneic stem cell transplantation for severe aplastic anemia. Bone Marrow Transplant 2007; 40:13.
- Kanda Y, Oshima K, Kako S, et al. In vivo T-cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA-mismatched haploidentical transplantation. Am J Hematol 2013; 88:294.
- Kang HJ, Shin HY, Park JE, et al. Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin conditioning regimen in unrelated transplantation for severe aplastic anemia: A phase II prospective multicenter study. Biol Blood Marrow Transplant 2010; 16:1582.
- George B, Mathews V, Viswabandya A, et al. Fludarabine based reduced intensity conditioning regimens in children undergoing allogeneic stem cell transplantation for severe aplastic anemia. Pediatr Transplant 2008; 12:14.
- Bacigalupo A, Socie' G, Lanino E, et al. 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. Haematologica 2010; 95:976.
- Anderlini P, Wu J, Gersten I, et al. Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol 2015; 2:e367.
- Hinterberger W, Rowlings PA, Hinterberger-Fischer M, et al. Results of transplanting bone marrow from genetically identical twins into patients with aplastic anemia. Ann Intern Med 1997; 126:116.
- Gerull S, Stern M, Apperley J, et al. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation. Haematologica 2013; 98:1804.
- Bacigalupo A, Socié G, Schrezenmeier H, et al. Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica 2012; 97:1142.
- Bacigalupo A, Socié G, Hamladji RM, et al. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica 2015; 100:696.
- Holtick U, Albrecht M, Chemnitz JM, et al. Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults. Cochrane Database Syst Rev 2014; :CD010189.
- Yoshimi A, Kojima S, Taniguchi S, et al. Unrelated cord blood transplantation for severe aplastic anemia. Biol Blood Marrow Transplant 2008; 14:1057.
- Chan KW, McDonald L, Lim D, et al. Unrelated cord blood transplantation in children with idiopathic severe aplastic anemia. Bone Marrow Transplant 2008; 42:589.
- Kang HJ, Lee JW, Kim H, et al. Successful first-line treatment with double umbilical cord blood transplantation in severe aplastic anemia. Bone Marrow Transplant 2010; 45:955.
- Yamamoto H, Kato D, Uchida N, et al. Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia. Blood 2011; 117:3240.
- Liu HL, Sun ZM, Geng LQ, et al. Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival. Bone Marrow Transplant 2012; 47:1186.
- Peffault de Latour R, Rocha V, Socié G. Cord blood transplantation in aplastic anemia. Bone Marrow Transplant 2013; 48:201.
- Ciceri F, Lupo-Stanghellini MT, Korthof ET. Haploidentical transplantation in patients with acquired aplastic anemia. Bone Marrow Transplant 2013; 48:183.
- Dufour C, Dallorso S, Casarino L, et al. Late graft failure 8 years after first bone marrow transplantation for severe acquired aplastic anemia. Bone Marrow Transplant 1999; 23:743.
- Eapen M, Le Rademacher J, Antin JH, et al. Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood 2011; 118:2618.
- Stucki A, Leisenring W, Sandmaier BM, et al. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Blood 1998; 92:2742.
- McCann SR, Bacigalupo A, Gluckman E, 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.
- Hernández-Boluda JC, Marín P, Carreras E, et al. Bone marrow transplantation for severe aplastic anemia: the Barcelona Hospital Clinic experience. Haematologica 1999; 84:26.
- Pantin J, Tian X, Shah AA, et al. Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes. Am J Hematol 2013; 88:874.
- Deeg HJ, Socié G, Schoch G, et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87:386.
- Socié G, Stone JV, Wingard JR, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med 1999; 341:14.
- Eapen M, Ramsay NK, Mertens AC, et al. Late outcomes after bone marrow transplant for aplastic anaemia. Br J Haematol 2000; 111:754.
- Storb R, Blume KG, O'Donnell MR, et al. Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers. Biol Blood Marrow Transplant 2001; 7:39.
- Sangiolo D, Storb R, Deeg HJ, et al. Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biol Blood Marrow Transplant 2010; 16:1411.
- Marsh JC, Pearce RM, Koh MB, et al. Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2014; 49:42.
- Deeg HJ, Leisenring W, Storb R, et al. Long-term outcome after marrow transplantation for severe aplastic anemia. Blood 1998; 91:3637.
- Gadalla SM, Wang T, Haagenson M, et al. Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA 2015; 313:594.
- Saad A, Mineishi S, Innis-Shelton R. Telomere length in hematopoietic stem cell transplantation for severe aplastic anemia: is it ready for "prime time"? JAMA 2015; 313:571.
- OVERVIEW OF APPROACH
- Decision to use HCT
- Patient/disease/donor factors
- Evidence for efficacy
- PRETRANSPLANT TESTING AND INTERVENTIONS
- Transfusion issues
- OVERVIEW OF HCT CONSIDERATIONS
- Preferred donor and preparative regimen
- - HLA-matched sibling donor
- - Matched unrelated donor
- - Haploidentical related donor
- - Identical twin (syngeneic) donor
- Preferred stem cell source
- GVHD and infection prophylaxis
- Graft failure/graft rejection
- Graft-versus-host disease
- Late malignancy
- Other late complications
- SURVIVAL AND QUALITY OF LIFE
- INVESTIGATIONAL STRATEGIES
- SUMMARY AND RECOMMENDATIONS