Immunosuppressive therapies in the management of immune-mediated marrow failures in adults: Where we stand and where we are going

British Journal of Haematology

Volumn 152, Issue 2, 2011, Pages 127-140

  Risitano, Antonio M ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Anti thymocyte globulin; Aplastic anaemia; Bone marrow failure; Ciclosporin A; Immunosuppression

Indexed keywords

ABATACEPT; ADALIMUMAB; ALEFACEPT; ALEMTUZUMAB; ATG FRESENIUS; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DACLIZUMAB; EFALIZUMAB; ETANERCEPT; FLUDARABINE; GRANULOCYTE COLONY STIMULATING FACTOR; INFLIXIMAB; LYMPHOCYTE ANTIBODY; LYMPHOGLOBULINE; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PENTOSTATIN; RAPAMYCIN; RITUXIMAB; STEROID; THYMOCYTE ANTIBODY; UNCLASSIFIED DRUG;

ANEMIA; APLASTIC ANEMIA; ARTICLE; BONE MARROW DEPRESSION; BONE MARROW DISEASE; BONE MARROW TOXICITY; CLINICAL TRIAL; CYTOPENIA; DRUG MECHANISM; DRUG MEGADOSE; DRUG RESPONSE; DRUG WITHDRAWAL; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INJECTION SITE REACTION; LARGE GRANULAR LYMPHOCYTE LEUKEMIA; LINEAGE RESTRICTED MARROW FAILURE; LOW DRUG DOSE; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PURE RED CELL ANEMIA; PURE WHITE CELL APLASIA; RISK FACTOR; SURVIVAL RATE; SURVIVAL TIME; T LYMPHOCYTE; TREATMENT FAILURE; WHOLE BODY RADIATION;

ADULT; ALGORITHMS; ANEMIA, APLASTIC; ANTILYMPHOCYTE SERUM; CYCLOSPORINE; HEMOGLOBINURIA, PAROXYSMAL; HISTORY, 20TH CENTURY; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS;

EID: 78650316570     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2010.08439.x     Document Type: Article

References (110)

1. Akashi, K., Shibuya, T., Taniguchi, S., Hayashi, S., Iwasaki, H., Teshima, T., Takamatsu, Y., Gondo, H., Okamura, T., Harada, M. & Niho, Y. (1999) Multiple autoimmune haemopoietic disorders and insidious clonal proliferation of large granular lymphocytes. British Journal of Haematology, 107, 670-673.
2. Alegre, M.L. & Fallarino, F. (2006) Mechanisms of CTLA-4-Ig in tolerance induction. Current Pharmaceutical Design, 12, 149-160.
3. Atta, E.H., Dias, D.S., Marra, V.L. & de Azevedo, A.M. (2010) Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study. Annals of Hematology, 89, 851-859.
4. Bacigalupo, A. (2007) Aplastic anemia: pathogenesis and treatment. Hematology American Society of Hematology Education Program, 2007, 23-28.
5. Bacigalupo, A., Chaple, M., Hows, J., Van Lint, M.T., McCann, S., Milligan, D., Chessells, J., Goldstone, A.H., Ottolander, J., van't Veer, E.T., Comotti, B., Coser, G., Broccia, A., Bosi, A., Locasciulli, A., Catalano, L., Battista, R., Arcese, W., Carotenuto, M., Marmont, A.M. & Gordon- Smith, E.C. (1993) Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ATG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party. British Journal of Haematology, 83, 145-151.
6. Bacigalupo, A., Bruno, B., Saracco, P., Di Bona, E., Locasciulli, A., Locatelli, F., Gabbas, A., Dufour, C., Arcese, W., Testi, G., Broccia, G., Carotenuto, M., Coser, P., Barbui, T., Leoni, P. & Ferster, A. (2000a) Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO). Blood, 95, 1931-1934.
7. Bacigalupo, A., Oneto, R., Bruno, B., Socié, G., Passweg, J., Locasciulli, A., Van Lint, M.T., Tichelli, A., McCann, S., Marsh, J., Ljungman, P., Hows, J., Marin, P. & Schrezenmeier, H. (2000b) Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation. Acta Haematologica, 103, 19-25.
8. Bacigalupo, A., Valle, M., Podestà, M., Pitto, A., Zocchi, E., De Flora, A., Pozzi, S., Luchetti, S., Frassoni, F., Van Lint, M.T. & Piaggio, G. (2005) T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia. Experimental Hematolology, 33, 819-827.
9. Bacigalupo, A., Socie', G., Lanino, E., Prete, A., Locatelli, F., Locasciulli, A., Cesaro, S., Shimoni, A., Marsh, J., Brune, M., Van Lint, M.T., Oneto, R. & Passweg, J.; Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation. (2010) 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, 95, 976-982.
10. Barrett, A.J. & Sloand, E. (2009) Autoimmune mechanisms in the pathophysiology of myelodysplastic syndromes and their clinical relevance. Haematologica, 94, 449-451.
11. Bible, K.C. & Tefferi, A. (1996) Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis. British Journal of Haematology, 93, 406-408.
12. Bourdage, J.S. & Hamlin, D.M. (1995) Comparative polyclonal antithymocyte globulin and antilymphocyte/antilymphoblast globulin anti-CD antigen analysis by flow cytometry. Transplantation, 59, 1194-1200.
13. Brodsky, R.A., Sensenbrenner, L.L. & Jones, R.J. (1996) Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation. Blood, 87, 491-494.
14. Brodsky, R.A., Chen, A.R., Dorr, D., Fuchs, E.J., Huff, C.A., Luznik, L., Smith, B.D., Matsui, W.H., Goodman, S.N., Ambinder, R.F. & Jones, R.J. (2010) High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood, 115, 2136-2141.
15. Calado, R.T. (2009) Telomeres and marrow failure. Hematology American Society of Hematology Education Program, 2009, 338-343.
16. Calado, R.T., Yewdell, W.T., Wilkerson, K.L., Regal, J.A., Kajigaya, S., Stratakis, C.A. & Young, N.S. (2009) Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood, 114, 2236-2243.
17. Camitta, B.M. (2000) What is the definition of cure for aplastic anemia? Acta Haematologica, 103, 16-18.
18. Cather, J.C., Cather, J.C. & Menter, A. (2003) Modulating T cell responses for the treatment of psoriasis: a focus on efalizumab. Expert Opinion of Biological Therapy, 3, 361-370.
19. Champlin, R., Ho, W. & Gale, R.P. (1983) Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial. New England Journal of Medicine, 308, 113-118.
20. Champlin, R.E., Ho, W.G., Feig, S.A., Winston, D.J., Lenarsky, C. & Gale, R.P. (1985) Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial Blood, 66, 184-188.
21. Dhodapkar, M.V., Li, C.Y., Lust, J.A., Tefferi, A. & Phyliky, R.L. (1994) Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood, 84, 1620-1627.
22. Di Bona, E., Rodeghiero, F., Bruno, B., Gabbas, A., Foa, P., Locasciulli, A., Rosanelli, C., Camba, L., Saracco, P., Lippi, A., Iori, A.P., Porta, F., De Rossi, G., Comotti, B., Iacopino, P., Dufour, C. & Bacigalupo, A. (1999) 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. Gruppo Italiano Trapianto di Midollo Osseo (GITMO). British Journal of Haematology, 107, 330-334.
23. Doney, K., Pepe, M., Storb, R., Bryant, E., Anasetti, C., Appelbaum, F.R., Buckner, C.D., Sanders, J., Singer, J., Sullivan, K., Weiden, P. & Hansen, J.A. (1992) Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone. Blood, 79, 2566-2571.
24. Dufour, C., Ferretti, E., Bagnasco, F., Burlando, O., Lanciotti, M., Ramenghi, U., Saracco, P., Van Lint, M.T., Longoni, D., Torelli, G.F., Pillon, M., Locasciulli, A., Misuraca, A., La Spina, M., Bacigalupo, A., Pistoia, V., Corcione, A., Svahn, J.; Marrow Failure Study Group of the AIEOP. (2009a) Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic anemia. Haematologica, 94, 1743-1747.
25. Dufour, C., Giacchino, R., Ghezzi, P., Tonelli, R., Ferretti, E., Pitto, A., Pistoia, V., Lanza, T. & Svahn, J. (2009b) Etanercept as a salvage treatment for refractory aplastic anemia. Pediatric Blood & Cancer, 52, 522-525.
26. Dumont, F.J. (2005) Fontolizumab Protein Design Labs. Current Opinion in Investigational Drugs, 6, 537-544.
27. Firkin, F.C., Prewett, E.J., Nicholls, K. & Moran, J. (1987) Antithymocyte globulin therapy for pure white cell aplasia. American Journal of Hematology, 25, 101-105.
28. Fouillard, L., Bensidhoum, M., Bories, D., Bonte, H., Lopez, M., Moseley, A.M., Smith, A., Lesage, S., Beaujean, F., Thierry, D., Gourmelon, P., Najman, A. & Gorin, N.C. (2003) Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma. Leukemia, 17, 474-476.
29. Frickhofen, N., Kaltwasser, J.P., Schrezenmeier, H., Raghavachar, A., Vogt, H.G., Herrmann, F., Freund, M., Meusers, P., Salama, A. & Heimpel, H. (1991) Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. New England Journal of Medicine, 324, 1297-1304.
30. Frickhofen, N., Heimpel, H., Kaltwasser, J.P., Schrezenmeier, H.; German Aplastic Anemia Study Group. (2003) Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood, 101, 1236-1242.
31. Fujishima, N., Sawada, K., Hirokawa, M., Oshimi, K., Sugimoto, K., Matsuda, A., Teramura, M., Karasawa, M., Arai, A., Yonemura, Y., Nakao, S., Urabe, A., Omine, M., Ozawa, K.; PRCA Collaborative Study Group. (2008) Long-term responses and outcomes following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia: a Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group. Haematologica, 93, 1555-1559.
32. Gluckman, E., Devergie, A., Poros, A. & Degoulet, P. (1982) Results of immunosuppression in 170 cases of severe aplastic anaemia. Report of the European Group of Bone Marrow Transplant (EGBMT). British Journal of Haematology, 51, 541-550.
33. Gluckman, E., Rokicka-Milewska, R., Hann, I., Nikiforakis, E., Tavakoli, F., Cohen-Scali, S. & Bacigalupo, A.; European Group for Blood and Marrow Transplantation Working Party for Severe Aplastic Anemia. (2002) 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. British Journal of Haematology, 119, 1075-1082.
34. Go, R.S., Li, C.Y., Tefferi, A. & Phyliky, R.L. (2001) Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood, 98, 483-485.
35. Gómez-Almaguer, D., Jaime- Pérez, J.C., Garza-Rodríguez, V., Chapa-Rodríguez, A., Tarín-Arzaga, L., Herrera- Garza, J.L., Ruiz-Argüelles, G.J., López-Otero, A., González-Llano, O. & Rodríguez-Romo, L. (2010) Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. Annals of Hematology, 89, 299-303.
36. Gupta, V., Gordon- Smith, E.C., Cook, G., Parker, A., Duguid, J.K., Wilson, K.M., Yi, Q.L. & Marsh, J.C. (2005) A third course of anti-thymocyte globulin in aplastic anaemia is only beneficial in previous responders. British Journal of Haematology, 129, 110-117.
37. van Kamp, H., Landegent, J.E., Jansen, R.P., Willemze, R. & Fibbe, W.E. (1991) Clonal hematopoiesis in patients with acquired aplastic anemia. Blood, 78, 3209-3214.
38. Kawano, Y., Nissen, C., Gratwohl, A. & Speck, B. (1988) Immunostimulatory effects of different antilymphocyte globulin preparations: a possible clue to their clinical effect. British Journal of Haematology, 68, 115-119.
39. Kim, H., Min, Y.J., Baek, J.H., Shin, S.J., Lee, E.H., Noh, E.K., Kim, M.Y. & Park, J.H. (2009) A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome. Leukemia Research, 33, 222-231.
40. Kochenderfer, J.N., Kobayashi, S., Wieder, E.D., Su, C. & Molldrem, J.J. (2002) Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. Blood, 100, 3639-3645.
41. Krueger, G.G. (2002) Selective targeting of T cell subsets: focus on alefacept - a remittive therapy for psoriasis. Expert Opinion on Biological Therapy, 2, 431-441.
42. Lim, Z.Y., Killick, S., Germing, U., Cavenagh, J., Culligan, D., Bacigalupo, A., Marsh, J. & Mufti, G.J. (2007) Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin. Leukemia, 21, 1436-1441.
43. Locasciulli, A., Arcese, W., Locatelli, F., DiBona, E. & Bacigalupo, A. (2001) Treatment of aplastic anaemia with granulocyte-colony stimulating factor and risk of malignancy. The Lancet, 357, 43-44.
44. Locasciulli, A., Oneto, R., Bacigalupo, A., Socié, G., Korthof, E., Bekassy, A., Schrezenmeier, H., Passweg, J. & Führer, M.; Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplant Group. (2007) Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica, 92, 11-18.
45. Loughran, Jr, T.P., Kidd, P.G. & Starkebaum, G. (1994) Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood, 84, 2164-2170.
46. Maciejewski, J.P. & Risitano, A.M. (2005) Aplastic anemia: management of adult patients. Hematology American Society of Hematology Education Program, 2005, 110-117.
47. Maciejewski, J.P., Selleri, C., Sato, T., Anderson, S. & Young, N.S. (1995) Increased expression of Fas antigen on bone marrow CD34+ cells of patients with aplastic anaemia. British Journal of Haematology, 91, 245-252.
48. Maciejewski, J.P., Selleri, C., Sato, T., Anderson, S. & Young, N.S. (1996) A severe and consistent deficit in marrow and circulating primitive hematopoietic cells (long-term culture-initiating cells) in acquired aplastic anemia. Blood, 88, 1983-1991.
49. Maciejewski, J.P., Follmann, D., Nakamura, R., Saunthararajah, Y., Rivera, C.E., Simonis, T., Brown, K.E., Barrett, J.A. & Young, N.S. (2001) Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood, 98, 3513-3519.
50. Maciejewski, J.P., Risitano, A., Sloand, E.M., Nunez, O. & Young, N.S. (2002a) Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Blood, 99, 3129-3135.
51. Maciejewski, J.P., Risitano, A.M., Sloand, E.M., Wisch, L., Geller, N., Barrett, J.A. & Young, N.S. (2002b) A pilot study of the recombinant soluble human tumour necrosis factor receptor (p75)-Fc fusion protein in patients with myelodysplastic syndrome. British Journal of Haematology, 117, 119-126.
52. Maciejewski, J.P., Sloand, E.M., Nunez, O., Boss, C. & Young, N.S. (2003) Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood, 102, 3584-3586.
53. Marsh, J. Making therapeutic decisions in adults with aplastic anemia. (2006) Hematology American Society Hematology Education Program, 2006, 78-85.
54. Marsh, J.C. & Gordon- Smith, E.C. (1988) The role of antilymphocyte globulin in the treatment of chronic acquired bone marrow failure. Blood Reviews, 2, 141-148.
55. Marsh, J.C., Ball, S.E., Cavenagh, J., Darbyshire, P., Dokal, I., Gordon- Smith, E.C., Keidan, J., Laurie, A., Martin, A., Mercieca, J., Killick, S.B., Stewart, R. & Yin, J.A.; British Committee for Standards in Haematology. (2009) Guidelines for the diagnosis and management of aplastic anaemia. British Journal of Haematology, 147, 43-70.
56. Mathé, G. & Schwarzenberg, L. (1976) Treatment of bone marrow aplasia by mismatched bone marrow transplantation after conditioning with antilymphocyte globulin - long-term results. Transplant Proceedings, 8, 595-602.
57. Maury, S., Bacigalupo, A., Anderlini, P., Aljurf, M., Marsh, J., Socié, G., Oneto, R. & Passweg, J.R.; Severe Aplastic Anemia Working Party, European Group for Blood and Marrow Transplantation (EBMT-SAAWP). (2009) Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen. Haematologica, 94, 1312-1315.
58. Mohan, S.R., Clemente, M.J., Afable, M., Cazzolli, H.N., Bejanyan, N., Wlodarski, M.W., Lichtin, A.E. & Maciejewski, J.P. (2009) Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia. Haematologica, 94, 1407-1414.
59. Nakao, S., Takami, A., Takamatsu, H., Zeng, W., Sugimori, N., Yamazaki, H., Miura, Y., Ueda, M., Shiobara, S., Yoshioka, T., Kaneshige, T., Yasukawa, M. & Matsuda, T. (1997) Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. Blood, 89, 3691-3699.
60. Niparuck, P., Atichartakarn, V. & Chuncharunee, S. (2008) Successful treatment of acquired amegakaryocytic thrombocytopenic purpura refractory to corticosteroids and intravenous immunoglobulin with antithymocyte globulin and cyclosporin. International Journal of Hematology, 88, 223-226.
61. Ohara, A., Kojima, S., Hamajima, N., Tsuchida, M., Imashuku, S., Ohta, S., Sasaki, H., Okamura, J., Sugita, K., Kigasawa, H., Kiriyama, Y., Akatsuka, J. & Tsukimoto, I. (1997) Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia. Blood, 90, 1009-1013.
62. Osuji, N., Matutes, E., Tjonnfjord, G., Grech, H., Del Giudice, I., Wotherspoon, A., Swansbury, J.G. & Catovsky, D. (2006) T-cell large granular lymphocyte leukemia: a report on the treatment of 29 patients and a review of the literature. Cancer, 107, 570-578.
63. de Planque, M.M., Bacigalupo, A., Würsch, A., Hows, J.M., Devergie, A., Frickhofen, N., Brand, A. & Nissen, C. (1989) Long-term follow-up of severe aplastic anaemia patients treated with antithymocyte globulin. Severe Aplastic Anaemia Working Party of the European Cooperative Group for Bone Marrow Transplantation (EBMT). British Journal of Haematology, 73, 121-126.
64. Raefsky, E.L., Gascon, P., Gratwohl, A., Speck, B. & Young, N.S. (1986) Biological and immunological characterization of ATG and ALG. Blood, 68, 712-719.
65. Raza, A., Candoni, A., Khan, U., Lisak, L., Tahir, S., Silvestri, F., Billmeier, J., Alvi, M.I., Mumtaz, M., Gezer, S., Venugopal, P., Reddy, P. & Galili, N. (2004) Remicade as TNF suppressor in patients with myelodysplastic syndromes. Leukemia & Lymphoma, 45, 2099-2104.
66. Risitano, A.M., Kook, H., Zeng, W., Chen, G., Young, N.S. & Maciejewski, J.P. (2002) Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by V beta CDR3 spectratyping and flow cytometry. Blood, 100, 178-183.
67. Risitano, A.M., Maciejewski, J.P., Green, S., Plasilova, M., Zeng, W. & Young, N.S. (2004) In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing. The Lancet, 364, 355-364.
68. Risitano, A.M., Selleri, C., Serio, B., Torelli, G.F., Kulagin, A., Maury, S., Halter, J., Gupta, V., Bacigalupo, A., Sociè, G., Tichelli, A., Schrezenmeier, H., Marsh, J., Passweg, J. & Rotoli, B.; Working Party Severe Aplastic Anaemia (WPSAA) of the European Group for Blood and Marrow Transplantation (EBMT). (2010) 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. British Journal of Haematology, 148, 791-796.
69. Rosenfeld, S.J., Kimball, J., Vining, D. & Young, N.S. (1995) Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood, 85, 3058-3065.
70. Rosenfeld, S., Follmann, D., Nunez, O. & Young, N.S. (2003) Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. The Journal of the American Medical Association, 289, 1130-1135.
71. Saracco, P., Quarello, P., Iori, A.P., Zecca, M., Longoni, D., Svahn, J., Varotto, S., Del Vecchio, G.C., Dufour, C., Ramenghi, U., Bacigalupo, A. & Locasciulli, A.; Bone Marrow Failure Study Group of the AIEOP (Italian Association of Paediatric Haematology Oncology). (2008) Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. British Journal of Haematology, 140, 197-205.
72. Saunthararajah, Y., Nakamura, R., Wesley, R., Wang, Q.J. & Barrett, A.J. (2003) A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood, 102, 3025-3027.
73. Sawada, K., Hirokawa, M., Fujishima, N., Teramura, M., Bessho, M., Dan, K., Tsurumi, H., Nakao, S., Urabe, A., Omine, M., Ozawa, K.; PRCA Collaborative Study Group. (2007) Long-term outcome of patients with acquired primary idiopathic pure red cell aplasia receiving cyclosporine A. A nationwide cohort study in Japan for the PRCA Collaborative Study Group. Haematologica, 92, 1021-1028.
74. Sawada, K., Fujishima, N. & Hirokawa, M. (2008) Acquired pure red cell aplasia: updated review of treatment. British Journal of Haematology, 142, 505-514.
75. Scheinberg, P., Nunez, O. & Young, N.S. (2006a) Re-treatment with rabbit antithymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia. British Journal of Haematology, 133, 622-627.
76. Scheinberg, P., Nunez, O., Wu, C. & Young, N.S. (2006b) Treatment of severe aplastic anaemia with combined immunosuppression: antithymocyte globulin, ciclosporin and mycophenolate mofetil. British Journal of Haematology, 133, 606-611.
77. Scheinberg, P., Wu, C.O., Nunez, O. & Young, N.S. (2009a) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. British Journal of Haematology, 144, 206-216.
78. Scheinberg, P., Wu, C.O., Nunez, O., Scheinberg, P., Boss, C., Sloand, E.M. & Young, N.S. (2009b) Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study. Haematologica, 94, 348-354.
79. Scheinberg, P., Marte, M., Nunez, O. & Young, N.S. (2010a) Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica, 95, 1075-1080.
80. Scheinberg, P., Cooper, J.N., Sloand, E.M., Wu, C.O., Calado, R.T. & Young, N.S. (2010b) Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. The Journal of the American Medical Association, 304, 1358-1364.
81. Sehgal, S.N. (1998) Rapamune® (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clinical Biochemistry, 31, 335-340.
82. Shimamoto, T., Tohyama, K., Okamoto, T., Uchiyama, T., Mori, H., Tomonaga, M., Asano, Y., Niho, Y., Teramura, M., Mizoguchi, H., Omine, M. & Ohyashiki, K. (2003) Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leukemia Research, 27, 783-788.
83. Sloand, E., Kim, S., Maciejewski, J.P., Tisdale, J., Follmann, D. & Young, N.S. (2002) Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia. Blood, 100, 1185-1191.
84. Sloand, E.M., Olnes, M.J., Shenoy, A., Weinstein, B., Boss, C., Loeliger, K., Wu, C.O., More, K., Barrett, A.J., Scheinberg, P. & Young, N.S. (2010) Alemtuzumab Treatment of Intermediate-1 Myelodysplasia Patients is Associated with Sustained Improvement in Blood Counts and Cytogenetic Remissions. J Clin Oncol. 2010 Nov 1. [Epub ahead of print].
85. Sloand, E.M., Olnes, M.J., Weinstein, B., Wu, C., Maciejewski, J., Scheinberg, P. & Young, N.S. (2010) Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab. Haematologica, 95, 382-387.
86. Smith, A.G., O' Reilly, R.J., Hansen, J.A. & Martin, P.J. (1985) Specific antibody-blocking activities in antilymphocyte globulin as correlates of efficacy for the treatment of aplastic anemia. Blood, 66, 721-723.
87. Socie, G., Mary, J.Y., Schrezenmeier, H., Marsh, J., Bacigalupo, A., Locasciulli, A., Fuehrer, M., Bekassy, A., Tichelli, A. & Passweg, J. (2007) Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT). Blood, 109, 2794-2796.
88. Socié, G., Henry-Amar, M., Bacigalupo, A., Hows, J., Tichelli, A., Ljungman, P., McCann, S.R., Frickhofen, N., Van't Veer-Korthof, E. & Gluckman, E. (1993) Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. The New England Journal of Medicine, 329, 1152-1157.
89. Speck, B., Gluckman, E., Haak, H.L. & van Rood, J.J. (1977) Treatment of aplastic anaemia by antilymphocyte globulin with and without allogeneic bone-marrow infusions. The Lancet, 2, 1145-1148.
90. Speck, B., Gratwohl, A., Nissen, C., Leibundgut, U., Ruggero, D., Osterwalder, B., Burri, H.P., Cornu, P. & Jeannet, M. (1981) Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation. British Medical Journal (Clinical Research Ed.), 282, 860-863.
91. Sternberg, A., Eagleton, H., Pillai, N., Leyden, K., Turner, S., Pearson, D., Littlewood, T. & Hatton, C. (2003) Neutropenia and anaemia associated with T-cell large granular lymphocyte leukaemia responds to fludarabine with minimal toxicity. British Journal of Haematology, 120, 699-701.
92. Sugimori, C., Chuhjo, T., Feng, X., Yamazaki, H., Takami, A., Teramura, M., Mizoguchi, H., Omine, M. & Nakao, S. (2006) Minor population of CD55- CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood, 107, 1308-1314.
93. Takamatsu, H., Espinoza, J.L., Lu, X., Qi, Z., Okawa, K. & Nakao, S. (2009) Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma. Journal of Immunology, 182, 703-710.
94. Teramura, M., Kimura, A., Iwase, S., Yonemura, Y., Nakao, S., Urabe, A., Omine, M. & Mizoguchi, H. (2007) Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood, 110, 1756-1761.
95. Thomas, E.D., Storb, R., Fefer, A., Slichter, S.J., Bryant, J.I., Buckner, C.D., Neiman, P.E., Clift, R.A., Funk, D.D. & Lerner, K.E. (1972) Aplastic anaemia treated by marrow transplantation. The Lancet, 1, 284-289.
96. Tichelli, A., Passweg, J., Nissen, C., Bargetzi, M., Hoffmann, T., Wodnar-Filipowicz, A., Signer, E., Speck, B. & Gratwohl, A. (1998) Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia. British Journal of Haematology, 100, 393-400.
97. Tichelli, A., Schrezenmeier, H., Socié, G., Marsh, J., Bacigalupo, A., Duehrsen, U., Franzke, A., Hallek, M., Thiel, E., Wilhelm, M., Höchsmann, B., Barrois, A., Champion, K. & Passweg, J.R. (2009) Use of G-CSF in patients with severe aplastic anemia treated with atg and cyclosporine increases neutrophils and decreases infection rates and hospitalization days but does not improve long-term outcome: results of a prospective, randomized clinical trial of the EBMT. Blood, 114, 496a.
98. Tisdale, J.F., Dunn, D.E., Geller, N., Plante, M., Nunez, O., Dunbar, C.E., Barrett, A.J., Walsh, T.J., Rosenfeld, S.J. & Young, N.S. (2000) High-dose cyclophosphamide in severe aplastic anaemia: a randomised trial. The Lancet, 356, 1554-1559.
99. Tisdale, J.F., Maciejewski, J.P., Nunez, O., Rosenfeld, S.J. & Young, N.S. (2002) Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial. Blood, 100, 4668-4670.
100. Vallejo, C., Montesinos, P., Rosell, A., Brunet, S., Córdoba, R., Pérez-Ceballos, E., Petit, J., Sevilla, J., Colado, E., Martín, A., Arranz, R., de la Serna, J., Espigado, I. & Cedillo, A. (2009) Comparison between lymphoglobuline- and thymoglobuline-based immunosuppressive therapy as first-line treatment for patients with aplastic anemia. Blood, 114, 3194a.
101. Viollier, R., Socié, G., Tichelli, A., Bacigalupo, A., Korthof, E.T., Marsh, J., Cornish, J., Ljungman, P., Oneto, R., Békássy, A.N., Fuehrer, M., Maury, S., Schrezenmeier, H., van Lint, M.T., Wojcik, D., Locasciulli, A. & Passweg, J.R. (2008) Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplantation, 41, 45-50.
102. Willis, F., Marsh, J.C.W., Bevan, D.H., Killick, S.B., Lucas, G., Griffiths, R., Ouwehand, W., Hale, G., Waldmann, H. & Gordon- Smith, E.C. (2001) The effect of treatment with Campath-1H in patients with autoimmune cytopenias. British Journal of Haematology, 114, 891-898.
103. Young, N.S. (2000) Acquired aplastic anemia. In: Bone Marrow Failure Syndromes (ed. by N.S. Young), pp. 1-46. WB Saunders, Philadelphia.
104. Young, N.S. & Maciejewski, J. (1997) The pathophysiology of acquired aplastic anemia. The New England Journal of Medicine, 336, 1365-1372.
105. Young, N., Griffith, P., Brittain, E., Elfenbein, G., Gardner, F., Huang, A., Harmon, D., Hewlett, J., Fay, J., Mangan, K., Morrison, F., Sensenbrenner, L., Shadduck, R., Wang, W., Zaroulis, C. & Zuckerman, K. (1988) A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood, 72, 1861-1869.
106. Young, N.S., Calado, R.T. & Scheinberg, P. (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood, 108, 2509-2519.
107. Zeng, W., Nakao, S., Takamatsu, H., Yachie, A., Takami, A., Kondo, Y., Sugimori, N., Yamazaki, H., Miura, Y., Shiobara, S. & Matsuda, T. (1999) Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. Blood, 93, 3008-3016.
108. Zheng, Y., Liu, Y. & Chu, Y. (2006) Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a prospective comparison of four different regimens. Experimental Hematology, 34, 826-831.
109. Zoumbos, N.C., Gascón, P., Djeu, J.Y., Trost, S.R. & Young, N.S. (1985a) Circulating activated suppressor T lymphocytes in aplastic anemia. The New England Journal of Medicine, 312, 257-265.
110. Zoumbos, N.C., Gascon, P., Djeu, J.Y. & Young, N.S. (1985b) Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proceedings National Academy of Sciences, 82, 188-192.