Leukemia Research
Volume 33, Issue 2 , Pages 222-231 , February 2009

A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome

Received 10 April 2008 ,Revised 26 June 2008 ,Accepted 4 August 2008.

References 

  1. Sugawara T, Endo K, Shishido T, Sato A, Kameoka J, Fukuhara O, et al. T cell-mediated inhibition of erythropoiesis in myelodysplastic syndromes. Am J Hematol. 1992;41:304–305
  2. Manz CY, Dietrich PY, Schnuriger V, Nissen C, Wodnar-Filipowicz A. T-cell receptor beta chain variability in bone marrow and peripheral blood in severe acquired aplastic anemia. Blood Cells Mol Dis. 1997;23:110–122
  3. Melenhorst JJ, Fibbe WE, Struyk L, van der Elsen PJ, Willemze R, Landegent JE. Analysis of T-cell clonality in bone marrow of patients with acquired aplastic anaemia. Br J Haematol. 1997;96:85–91
  4. Molldrem JJ, Jiang YZ, Stetler-Stevenson M, Mavroudis D, Hensel N, Barrett AJ. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br J Haematol. 1998;102:1314–1322
  5. Kochenderfer JN, Kobayashi S, Wieder ED, Su C, Molldrem JJ. Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. Blood. 2002;100:3639–3645
  6. Kaulen DR, Golovanova TA, Pyatikhina DP, Khorobrikh VV. Inhibition of haemopoietic stem cells by syngeneic lymphocytes treated with antilymphocyte serum. Folia Biol (Praha). 1975;21:95–102
  7. Jansen J, Veenhof WF, Goselink HM. Anti-thymocyte globulin effective in the treatment of aplastic anemia does not stimulate granulocyte precursor cells. Exp Hematol. 1981;9:1028–1034
  8. Doney K, Martin P, Storb R, Whitehead J, Smith A, Hansen JA, et al. A randomized trial of antihuman thymocyte globulin versus murine monoclonal antihuman T-cell antibodies as immunosuppressive therapy for aplastic anemia. Exp Hematol. 1985;13:520–524
  9. Huang AT, Mold NG, Zhang SF. Antithymocyte globulin stimulates human hematopoietic progenitor cells. Proc Natl Acad Sci USA. 1987;84:5942–5946
  10. Tong J, Bacigalupo A, Piaggio G, Figari O, Marmont A. Effect of antilymphocyte globulin (ALG) on bone marrow T/non-T cells from aplastic anaemia patients and normal controls. Br J Haematol. 1989;73:546–550
  11. Franzke A, Geffers R, Hunger JK, Pfortner S, Piao W, Ivanyi P, et al. Identification of novel regulators in T-cell differentiation of aplastic anemia patients. BMC Genom. 2006;7:263
  12. Gluckman E, Esperou-Bourdeau H, Baruchel A, Boogaerts M, Briere J, Donadio D, et al. Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. Blood. 1992;79:2540–2546
  13. Marsh J, Schrezenmeier H, Marin P, Ilhan O, Ljungman P, McCann S, et al. Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party. Blood. 1999;93:2191–2195
  14. Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F, et al. 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. 2000;95:1931–1934
  15. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H, et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood. 2000;96:2049–2054
  16. Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003;101:1236–1242
  17. 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
  18. Teramura M, Kimura A, Iwase S, Yonemura Y, Nakao S, Urabe A, et al. 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. 2007;110:1756–1761
  19. 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
  20. Greenwood J, Gorman SD, Routledge EG, Lloyd IS, Waldmann H. Engineering multiple-domain forms of the therapeutic antibody CAMPATH-1H: effects on complement lysis. Ther Immunol. 1994;1:247–255
  21. Williams RJ, Clarke E, Blair A, Evely R, Hale G, Waldmann H, et al. Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G. Cytotherapy. 2000;2:5–14
  22. Nuckel H, Frey UH, Roth A, Duhrsen U, Siffert W. Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity. Eur J Pharmacol. 2005;514:217–224
  23. Willis F, Marsh JC, Bevan DH, Killick SB, Lucas G, Griffiths R, et al. The effect of treatment with Campath-1H in patients with autoimmune cytopenias. Br J Haematol. 2001;114:891–898
  24. Ru X, Liebman HA. Successful treatment of refractory pure red cell aplasia associated with lymphoproliferative disorders with the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). Br J Haematol. 2003;123:278–281
  25. Au WY, Lam CC, Chim CS, Pang AW, Kwong YL. Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia. Leuk Res. 2005;29:1213–1215
  26. Schutzinger C, Gaiger A, Thalhammer R, Vesely M, Fritsche-Polanz R, Schwarzinger I, et al. Remission of pure red cell aplasia in T-cell receptor gammadelta-large granular lymphocyte leukemia after therapy with low-dose alemtuzumab. Leukemia. 2005;19:2005–2008
  27. Lee JH, Lee JH, Choi SJ, Lee KH. Alemtuzumab treatment for aplastic anemia and low risk myelodysplastic syndrome: preliminary results. Proc Kor Soc Hematol. 2007;42:88
  28. Frickhofen N, Rosenfeld SJ. Immunosuppressive treatment of aplastic anemia with antithymocyte globulin and cyclosporine. Semin Hematol. 2000;37:56–68
  29. Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997;336:1365–1372
  30. 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
  31. Watanabe T, Masuyama J, Sohma Y, Inazawa H, Horie K, Kojima K, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120:247–259
  32. Shah A, Lowenstein H, Chant A, Khan A. CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro. Transpl Int. 2006;19:749–758
  33. Rowan WC, Hale G, Tite JP, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) triggers activation of normal human T lymphocytes. Int Immunol. 1995;7:69–77
  34. Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood. 1993;82:807–812
  35. Wing MG, Moreau T, Greenwood J, Smith RM, Hale G, Isaacs J, et al. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. J Clin Invest. 1996;98:2819–2826
  36. Rowan W, Tite J, Topley P, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. 1998;95:427–436
  37. Rezvany MR, Tehrani MJ, Karlsson C, Lundin J, Rabbani H, Osterborg A, et al. Reconstitution of the T-cell repertoire following treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with B-cell chronic lymphocytic leukaemia. Br J Haematol. 2006;135:475–485
  38. Kirsch BM, Haidinger M, Zeyda M, Bohmig GA, Tombinsky J, Muhlbacher F, et al. Alemtuzumab (Campath-1H) induction therapy and dendritic cells: Impact on peripheral dendritic cell repertoire in renal allograft recipients. Transpl Immunol. 2006;16:254–257
  39. Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003;289:1130–1135
  40. Kim I, Yoon SS, Park S, Kim BK, Kim NK. The treatment of severe aplastic anemia: outcomes of bone marrow transplantation and immunosuppressive therapy in a single institution of Korea. J Kor Med Sci. 2003;18:365–371
  41. Ahn MJ, Choi JH, Lee YY, Choi IY, Kim IS, Yoon SS, et al. Outcome of adult severe or very severe aplastic anemia treated with immunosuppressive therapy compared with bone marrow transplantation: multicenter trial. Int J Hematol. 2003;78:133–138
  42. Tichelli A, Gratwohl A, Wuersch A, Nissen C, Speck B. Antilymphocyte globulin for myelodysplastic syndrome. Br J Haematol. 1988;68:139–140
  43. Young N, Griffith P, Brittain E, Elfenbein G, Gardner F, Huang A, et al. A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood. 1988;72:1861–1869

PII: S0145-2126(08)00363-9

doi: 10.1016/j.leukres.2008.08.004

Leukemia Research
Volume 33, Issue 2 , Pages 222-231 , February 2009

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