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Treatment of refractory or relapsed acquired aplastic anemia: review of established and experimental approaches

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Pages 1435-1445 | Received 20 Aug 2010, Accepted 28 Feb 2011, Published online: 03 Jun 2011

References

  • Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509–2519.
  • Füreder W, Krauth MT, Sperr WR, et al. Evaluation of angiogenesis and vascular endothelial growth factor expression in the bone marrow of patients with aplastic anemia. Am J Pathol 2006;168:123–130.
  • Chao YH, Peng CT, Harn HJ, Chan CK, Wu KH. Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia. Ann Hematol 2010;89:715–723.
  • Gupta P, Khurana N, Singh T, Gupta D, Dhingra KK. Bone marrow angiogenesis in aplastic anemia–a study of CD34 and VEGF expression in bone marrow biopsies. Hematology 2009;14:16–21.
  • Hirano N, Butler MO, von Bergwelt-Baildon MS, et al. Autoantibodies frequently detected in patients with aplastic anemia. Blood 2003;102:4567–4575.
  • Feng X, Chuhjo T, Sugimori C, et al. Diazepam-binding inhibitor-related protein 1: a candidate autoantigen in acquired aplastic anemia patients harboring a minor population of paroxysmal nocturnal hemoglobinuria-type cells. Blood 2004;104:2425–2431.
  • Takamatsu H, Feng X, Chuhjo T, et al. Specific antibodies to moesin, a membrane-cytoskeleton linker protein, are frequently detected in patients with acquired aplastic anemia. Blood 2007;109:2514–2520.
  • Young NS, Bacigalupo A, Marsh JCW. Aplastic anemia: pathophysiology and treatment. Biol Blood Marrow Transplant 2010;16(1 Suppl.):119–125.
  • Marsh JCW, Ball SE, Cavenagh J, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009;147:43–70.
  • Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H. Antithymocyte globulin with or without cyclosporine A: 11-year follow up of a randomized trial comparing treatments of aplastic anemia. Blood 2003;101:1236–1242.
  • Maciejewski JP, Risitano A, Sloand EM, Nunez O, Young NS. Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Blood 2002;99:3129–3135.
  • Sugimori C, Chuhjo T, Feng X, et al. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 2006;107:1308–1314.
  • Scheinberg P, Wu CO, Nunez O, Young NS. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 2009;144:206–216.
  • Chang MH, Kim KH, Kim HS, et al. Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia. Eur J Haematol 2010;84:154–159.
  • Song MK, Chung JS, Joo YD, et al. Is the early cyclosporine A level predictive of the outcome of immunosuppressive therapy in severe aplastic anemia? Eur J Haematol 2009;83:72–78.
  • Führer M, Rampf U, Baumann I, et al. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood 2005;106:2102–2104.
  • Tichelli A, Socié G, Henry-Amar M, et al. Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party. Ann Intern Med 1999;130:193–201.
  • Saunthararajah Y, Nakamura R, Nam JM, et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 2002;100:1570–1574.
  • Hendry CL, Sivakumaran M, Marsh JCW, Gordon-Smith EC. Relapse of severe aplastic anaemia after influenza immunization. Br J Haematol 2002;119:283–284.
  • Tichelli A, Socie G, Marsh J, et al. Outcome of pregnancy and disease outcome among women with aplastic anemia treated with immunosuppression. Ann Intern Med 2002;137:164–172.
  • Kahl C, Leisenring W, Deeg HJ, et al. Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br J Haematol 2005;130: 747–751.
  • Schrezenmeier H, Marin P, Raghavachar A, et al. Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party. Br J Haematol 1993;85:371–377.
  • Bacigalupo A, Passweg J. Diagnosis and treatment of acquired aplastic anemia. Hematol Oncol Clin North Am 2009;23:159–170.
  • Atta EH, Dias DS, Marra VL, de Azevedo AM. Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol 2010;89:851–859.
  • Gluckman E, Rokicka-Milewska R, Hann I, et al. Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br J Haematol 2002;119:1075–1082.
  • Camitta BM. What is the definition of cure for aplastic anemia? Acta Haematol 2000;103:16–18.
  • Marsh JCW, Ball SE, Cavenagh J, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009;147:43–70.
  • Di Bona E, Rodeghiero F, Bruno B, et al. 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. Br J Haematol 1999;107:330–334.
  • Scheinberg P, Nunez O, Young NS. Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia. Br J Haematol 2006;133:622–627.
  • Tichelli A, Passweg J, Nissen C, et al. Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia. Br J Haematol 1998;100:393–400.
  • Gupta V, Gordon-Smith EC, Cook G, et al. A third course of anti-thymocyte globulin in aplastic anaemia is only beneficial in previous responders. Br J Haematol 2005;129:110–117.
  • Bacigalupo A, Locatelli F, Lanino E, et al. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant 2005;36:947–950.
  • Deeg HJ, O'Donnell M, Tolar J, et al. Optimization of conditioning for marrow transplantation from unrelated donors for patients with aplastic anemia after failure of immunosuppressive therapy. Blood 2006;108:1485–1491.
  • Gupta V, Ball SE, Sage D, et al. Marrow transplants from matched unrelated donors for aplastic anaemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning. Bone Marrow Transplant 2005;35:467–471.
  • Maury S, Balère-Appert ML, Chir Z, et al. Unrelated stem cell transplantation for severe acquired aplastic anemia:improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica 2007;92:589–596.
  • Passweg JR, Pérez WS, Eapen M, et al. Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia. Bone Marrow Transplant 2006; 37:641–649.
  • Kojima S, Matsuyama T, Kato S, et al. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood 2002;100:799–803.
  • 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;95:976–982.
  • Deeg HJ, Seidel K, Casper J, et al. Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy. Biol Blood Marrow Transplant 1999;5:243–252.
  • Woodard P, Cunningham JM, Benaim E, et al. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant 2004;33:411–418.
  • Urban C, Benesch M, Sykora KW, Schwinger W, Lackner H. Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Bone Marrow Transplant 2005;35:591–594.
  • Lacerda JF, Martins C, Carmo JA, et al. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant 2005;11:399–400.
  • Tsutsumi Y, Tanaka J, Miura T, et al. Successful non-T-cell depleted nonmyeloablative hematopoietic stem cell transplantation (NST) from an HLA-haploidentical 3 loci-mismatched sibling in a heavily transfused patient with severe aplastic anemia based on the fetomaternal microchimerism. Bone Marrow Transplant 2004;34:267–269.
  • Kremens B, Basu O, Grosse-Wilde H, Sauerwein W, Schaefer UW, Havers W. Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia. Bone Marrow Transplant 2001;27:111–113.
  • Schwinger W, Urban C, Lackner H, et al. Unrelated peripheral blood stem cell transplantation with ‘megadoses’ of purified CD34+ cells in three children with refractory severe aplastic anemia. Bone Marrow Transplant 2000;25:513–517.
  • Gluckman E, Rocha V, Boyer-Chammard A, et al. Outcome of cord-blood transplantation from related and unrelated donors. N Engl J Med 1997;337:373–381.
  • Lee JW, Kang HJ, Kim EK, Shin HY, Ahn HS. Successful salvage unrelated umbilical cord blood transplantation with two units after engraftment failure with single unit in severe aplastic anemia. J Korean Med Sci 2009;24:744–746.
  • Ohga S, Ichino K, Goto K, et al. Unrelated donor cord blood transplantation for childhood severe aplastic anemia after a modified conditioning. Pediatr Transplant 2006;10:497–500.
  • Tajika K, Mizuki T, Nakayama K, Yamaguchi H, Dan K. Umbilical-cord blood cell transplantation conditioned with a reduced intensity-regimen is a practical salvage therapy for severe aplastic anemia refractory to immunosuppressive therapy with antithymocyte globulin/ciclosporin. J Nippon Med Sch 2007;74:424–429.
  • Mao P, Wang S, Wang S, et al. Umbilical cord blood transplant for adult patients with severe aplastic anemia using anti-lymphocyte globulin and cyclophosphamide as conditioning therapy. Bone Marrow Transplant 2004;33:33–38.
  • Mao P, Zhu Z, Wang H, et al. Sustained and stable hematopoietic donor-recipient mixed chimerism after unrelated cord blood transplantation for adult patients with severe aplastic anemia. Eur J Haematol 2005;75:430–435.
  • Peffault de Latour R, Purtill D, Ruggeri A, et al. Influence of nucleated cell dose on overall survival of unrelated cord blood transplant for patients with severe acquired aplastic anemia: a study by EUROCORD and the Aplastic Anemia Working Party of the EBMT. Biol Blood Marrow Transplant 2010;17:78–85.
  • Bacigalupo A, Piaggio G, Podestá M, et al. Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor. Blood 1993;82:1410–1414.
  • Sloand EM, Read EJ, Scheinberg P, et al. Mobilization, collection, and immunomagnetic selection of peripheral blood CD34 cells in recovered aplastic anemia patients. Transfusion 2007;47:1250–1253.
  • Risitano AM, Selleri C, Serio B, et al. Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single-lineage marrow failure: a pilot study and a survey from the EBMT WPSAA. Br J Haematol 2010;148: 791–796.
  • Kim H, Min YJ, Baek JH, et al. A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome. Leuk Res 2009;33:222–231.
  • Gómez-Almaguer D, Jaime-Pérez JC, Garza-Rodríguez V, et al. Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. Ann Hematol 2010;89:299–303.
  • Brodsky RA, Sensenbrenner LL, Jones RJ. Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation. Blood 1996; 87:491–494.
  • Brodsky RA, Petri M, Smith BD, et al. Immunablative high dose cyclophosphamide without stem cell rescue for refractory, severe autoimmune disease. Ann Intern Med 1998;129: 1031–1035.
  • Brodsky RA, Chen AR, Brodsky I, Jomes RJ. High dose cyclophosphamide as salvage therapy for severe aplastic anemia. Exp Hematol 2004;32:435–440.
  • Brodsky RA, Chen AR, Dorr D, et al. High dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood 2010;115:2136–2141.
  • Audino AN, Blatt J, Carcamo B, et al. High-dose cycloophosphamide treatment for refractory severe aplastic anemia in children. Pediatr Blood Cancer 2010;54:269–272.
  • Tisdale JF, Dunn DE, Geller N, et al. High-dose cyclophosphamide in severe aplastic anaemia: a randomised trial. Lancet 2000;356:1554–1559.
  • Tisdale JF, Maciejewski JP, Nuñez O, Rosenfeld SJ, Young NS. Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial. Blood 2002;100:4668–4670.
  • Socié G. Cyclophosphamide in aplastic anemia? Blood 2010;115:2120–2121.
  • Camitta B, Thomas ED, Nathan DG, et al. A prospective study of androgens and bone marrow transplantation for tretament of severe aplastic anemia. Blood 1979;53:504–514.
  • Champlin RE, Ho WG, Feig SA, Winston DJ, Lenarsky C, Gale RP. Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial. Blood 1985;66:184–188.
  • Bacigalupo A, Chaple M, Hows J, et al. Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party. Br J Haematol 1993;83:145–151.
  • Shahidi NT, Diamond LK. Testosterone-induced remission in aplastic anemia of both acquired and congenital types. Further observations in 24 cases. N Engl J Med 1961;264: 953–967.
  • Calado RT, Yewdell WT, Wilkerson KL, et al. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood 2009;114:2236–2243.
  • Yamaguchi H, Calado RT, Ly H, et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 2005;352:1413–1424.
  • Haneline LS. TERTrific hormones promote hematopoiesis. Blood 2009;114:2207–2208.
  • Chuhjo T, Yamazaki H, Omine M, Nakao S. Danazol therapy for aplastic anemia refractory to immunosuppressive therapy. Am J Hematol 2008;83:387–389.
  • Dufour C, Corcione A, Svahn J, Haupt R, Battilana N, Pistoia V. Interferon gamma and tumour necrosis factor alpha are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia. Br J Haematol 2001;115:1023–1031.
  • Dufour C, Corcione A, Svahn J, et al. TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro. Blood 2003;102:2053–2059.
  • Dufour C, Giacchino R, Ghezzi P, et al. Etanercept as a salvage treatment for refractory aplastic anemia. Pediatr Blood Cancer 2009;52:522–525.
  • Usuki K, Iki S, Arai S, Iijima K, Takaku F, Urabe A. Stable response after administration of stem cell factor combined with granulocyte colony-stimulating factor in aplastic anemia. Int J Hematol 2006;83:404–407.
  • Kurzrock R. Thrombopoietic factors in chronic bone marrow failure states: the platelet problem revisited. Clin Cancer Res 2005;11:1361–1367.
  • Herbert KE, Prince HM, Ritchie DS, Seymour JF. The role of ancestim (recombinant human stem-cell factor, rhSCF) in hematopoietic stem cell mobilization and hematopoietic reconstitution. Expert Opin Biol Ther 2010;10:113–125.
  • Schrezenmeier H, Marsh JC, Stromeyer P, et al. A phase I/II trial of recombinant human interleukin-6 in patients with aplastic anaemia. Br J Haematol 1995;90:283–292.
  • Tsimberidou AM, Giles FJ, Khouri I, et al. Low-dose interleukin-11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center experience. Ann Oncol 2005;16:139–145.
  • Wu HH, Talpaz M, Champlin RE, Pilat SR, Kurzrock R. Sequential interleukin 3 and granulocyte-macrophage-colony stimulating factor therapy in patients with bone marrow failure with long-term follow-up of responses. Cancer 2003;98:2410–2419.
  • Hansen PB, Lauritzen AM. Aplastic anemia successfully treated with rituximab. Am J Hematol 2005;80:292–294.
  • Castiglioni MG, Scatena P, Pandolfo C, Mechelli S, Bianchi M. Rituximab therapy of severe aplastic anemia induced by fludarabine and cyclophosphamide in a patient affected by B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2006;47: 1985–1986.
  • Waldmann TA. Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune disease, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 2007;27:1–18.
  • Maciejewski JP, Sloand EM, Nunez O, Boss C, Young NS. Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood 2003;102:3584–3586.
  • Sloand EM, Olnes MJ, Weinstein B, et al. Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab. Haematologica 2010;95:382–387.
  • Schrezenmeier H, Bacigalupo A, Dohner H, et al. Mycophenolate mofetil as treatment of patients with acquired aplastic anaemia failing to durably respond to standard immunosuppressive treatment. Bone Marrow Transplant 2003;31(Suppl. 1): Abstract 0363.
  • Scheinberg P, Nunez O, Wu C, Young NS. Treatment of severe aplastic anaemia with combined immunosuppression:anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol 2006;133:606–611.
  • Scheinberg P, Wu CO, Nunez O, et al. Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica 2009;94:348–354.

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