Haematologica 2000;85:supplement to no. 10 - Supplements ...

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Immune Tolerance and the Treatment of Hemophilacs with an Inhibitor 39 suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci USA 1994; 91:6688-92. 17. DiMichele DM. Immune tolerance: a synopsis of the international experience. Haemophilia 1998; 4:568- 73. 18. Mariani G, Kroner, B. International immune tolerance registry, 1997 update. Vox Sang 1999; 77 (suppl 1):25-7. 19. Peitsch MC, Jongeneel CV. A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors. Int Immunol 1993; 5:233- 8. 20. Nishioka Y, Lipsky PE. The role of CD40-CD40 ligand interaction in human T cell-B cell collaboration. J Immunol 1994; 153:1027-36. 21. Foy TM, Aruffo A, Bajorath J, Buhlmann JE, Noelle RJ. Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol. 1996; 14:591-617. 22. Grewel IS, Flavell RA. A central role of CD40 ligand in the regulation of CD4+ T cell responses. Immunol Today 1996; 17:410-4. 23. Noelle RJ, Mackey M, Foy T, Buhlman J, Burns C. CD40 and its ligand in autoimmunity. Ann N Y Acad Sci 1997; 815:384-91. 24. Allen RC, Armitage RJ, Conley ME, et al. 1993. CD40 ligand causes X-linked immunodeficiency with hyper- IgM. Nature 361: 539-41. 25. Korthauer U, Graf D, Mages HW, et al. Defective expression of T cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature 1993; 361:539-41. 26. Reding MT, Wu H, Krampf M, et al. CD4+ T cell response to factor VIII in hemophilia A, acquired hemophilia, and healthy subjects. Thromb Haemost 1999; 82:509-15. Haematologica vol. 85(supplement to n. 10):October 2000
Haematologica 2000; 85(suppl. to n.10) p. 40-44 Registries of Immunotolerance Protocol The Maintenence of Tolerance after Successful Immune Tolerance Induction in Hemophilia A and B: The North American Registry D. DIMICHELE, B. KRONER AND THE FACTOR VIII / IX SUBCOMMITTEE OF THE INTERNATIONAL SOCIETY FOR THROMBOSIS AND HEMOSTASIS Cornell and the Research Triangle Institute, New York, NY and Rockville, MD, USA Abstract The North American Immune Tolerance Registry (NAITR) was initiated with the goal of determining, by questionnaire, immune tolerance (ITT) practices in hemophilia treatment centers in Canada and the United States. Sixty-eight centers (40%) responded. Of the 130 registry subjects with hemophilia A who completed ITT, 93 (72%) achieved tolerance. Of the 11 completed ITT courses in patients with hemophilia B, 4 (36%) were successful. Maintenance therapy was defined as any clotting factor regimen administered subsequent to the patient achieving the treating physician's criteria for successful immune tolerance. Seventy-five (81%) of 93 individuals in the hemophilia A cohort who successfully achieved tolerance were maintained on a regular (prophylactic factor VIII (FVIII) regimen for a variable time period post-ITT. The median dose used was 150 units/kg/week (range: 17-700). Forty-eight (64%) subjects remained tolerant while receiving regular doses of FVIII for a median observation period of 13 months (range 0-129 months). Of 27 patients whose maintenance therapy had been stopped, 17 (68%) remained tolerant over a median period of 19 months (range 1-54 months) and 9 relapsed. Among the relapses, 3 occurred after maintenance therapy was stopped; 6 were noted on prophylactic FVIII at a median time of 11 months (range 2-61 months). The definition of tolerance was reviewed for the 9 subjects who relapsed and was defined by a normal recovery and survival in only 1/9 patients. Among the 11 hemophilia B subjects in the cohort who completed tolerance, 4 had a successful outcome. Four individuals were placed on maintenance regimens of 25-100 units FIX/kg/day and all remained tolerant. ©2000, Ferrata Storti Foundation Key Words: hemophilia A, hemophilia B, immune tolerance, inhibitors Correspondence: Donna DiMichele, MD, New York Presbyterian Hospital - Cornell University, 525 East 68th Street, Room P-695, New York, NY 10021 - Phone: international +212-746-3418 - Fax: international +212-746-8986 - E-mail: dmdimich@mail.med.cornell.edu The North American Immune Tolerance Registry (NAITR) was a project of the ISTH Factor VIII/IX Subcommittee conceived in 1992 by Dr. Carol Kasper. The NAITR was initiated with the goal of further determining immune tolerance (ITT) practices in Canada and the United States with respect to the identification of 1) therapeutic regimens in use; 2) therapeutic outcomes; 3) predictors of successful outcome, 4) complications of therapy and 5) the maintenance of successful tolerance over time. We now report the data accumulated from the NAITR between March 1993 and August 1997 with respect to maintenance of tolerance after successful induction in hemophilia A and B inhibitor patients. Design and Methods Data collection Data collection forms were initially sent in March 1993 to 168 hemophilia treatment centers (HTCs) in the United States (US) and Canada. Data updates were requested from participating HTCs in March 1994 and April 1996. The last update on the data set was performed in August 1997 to include several additional participating centers. Data forms were completed by the HTC medical directors or hemophilia nursing staff. The collection tool was intended to study the following parameters: 1) the frequency of past and current use of ITT among hemophilia A and B patients with inhibitors; 2) the therapeutic regimens in use including treatment product purity, dosing and duration of therapy; 3) the clinical outcome (success or failure) relative to the following aspects of treatment: a) duration of ITT; b) interval between inhibitor diagnosis and initiation of ITT; c) age at ITT induction; d) HIV status; e) race; f) and inhibitor titers including i) historical pre-ITT peak; ii) titer immediately prior to ITT induction (pre-induction titer) and iii) peak titer on ITT. Data were also collected on dosing and product regimens Haematologica vol. 85(supplement to n. 10):October 2000
Page 1 and 2: Haematologica established in 1920 e
Page 3 and 4: Acknowledgments We wish to thank th
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Page 11 and 12: 8 J. Oldenburg et al. Tuddenham et
Page 13 and 14: 10 J. Oldenburg et al. Table 4. Mut
Page 15 and 16: 12 J. Oldenburg et al. reactions ac
Page 17 and 18: 14 J. Oldenburg et al. Dr. Schwaab
Page 19 and 20: 16 J. Ingerslev be established more
Page 21 and 22: 18 J. Ingerslev sion monitoring dem
Page 23 and 24: 20 J. Ingerslev REFERENCES 1. Hay C
Page 25 and 26: 22 CRM Hay Side effects of Hyate:C
Page 27 and 28: 24 CRM Hay tion by porcine factor V
Page 31 and 32: 28 P. Lollar these epitopes by site
Page 33 and 34: 30 P. Lollar titer and an anti-porc
Page 35 and 36: 32 Immune Tolerance and the Treatme
Page 37 and 38: 34 Immune Tolerance and the Treatme
Page 39 and 40: 36 B.M. Ewenstein et al. exposed, 7
Page 41: 38 B.M. Ewenstein et al. Table 1. H
Page 45 and 46: 42 D. DiMichele et al. Discussion T
Page 47 and 48: 44 D. DiMichele et al. Italy and in
Page 49 and 50: 46 H. Lenk et al. Figure 1. Maximum
Page 53 and 54: 50 E. Berntorp et al. standing inhi
Page 57 and 58: 54 C.R.M. Hay Logistic barriers to
Page 59 and 60: 56 C.R.M. Hay ed to go for a fully
Page 61 and 62: 58 C.M. Kessler hemophilia A, have
Page 63 and 64: 60 C.M. Kessler in eradicating allo
Page 65 and 66: 62 C.M. Kessler ously. Do you see d
Page 69 and 70: 66 L. Nemes et al. Figure 1. A gian
Page 71 and 72: 68 L. Nemes et al. trast to the ear
Page 73 and 74: 70 E. Berntorp Hemophilia A severe
Page 75 and 76: 72 E. Berntorp VIII. MARIANI: It wo
Page 77 and 78: 74 R. Landolfi et al. Table 1. Resu
Page 79 and 80: 76 H-H. Brackmann et al. Table 1a.
Page 83 and 84: 80 R.B. Butler of progress and perm
Page 85 and 86: 82 B. Gargallo emotional consequenc
Page 87 and 88: 84 L.M. Aledort et al. Success rate
Page 91 and 92: 88 D. Scandella et al. Seven non-in
Page 93 and 94:
90 S. Lacroix-Desmazes et al. demon
Page 95 and 96:
92 S. Lacroix-Desmazes et al. 244:1
Page 97 and 98:
94 J-M.R. Saint-Remy linking of sur
Page 99 and 100:
96 J-M.R. Saint-Remy identification
Page 101 and 102:
98 M.D. Kazatchkine et al. normal l
Page 103 and 104:
Haematologica 2000; 85(suppl. to n.
Page 105 and 106:
102 L.W. Hoyer et al. have prevente
Page 107 and 108:
104 J.G. Gilles et al. Table 1. The
Page 109 and 110:
106 J.G. Gilles et al. typic intera
Page 111 and 112:
Haematologica 2000; 85(suppl. to n.
Page 113 and 114:
110 D. Lillicrap a transgene in tis
Page 115 and 116:
112 D. Lillicrap DI MICHELE: I am a
Page 117 and 118:
114 G.C. White et al. cost, time, a
Page 119 and 120:
116 G.C. White et al. Blood 62:141-
Page 121:
II Immune Tolerance and the Treatme
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