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

More documents

Recommendations

Info

Immune Tolerance and the Treatment of Hemophilacs with an Inhibitor 55 Tolerance Registry and the North American Immune Tolerance Registry. Vox Sang 1999; 77:33-7. 11. Smith MP, Spence KJ, Waters EL, et al. Immune tolerance therapy for haemophilia A patients with acquired factor VIII allo-antibodies: comprehensive analysis of experience in a single institution. Thromb Haemost 1999; 81:35-8. 12. Rocino A, DiBiasi R. Successful immune tolerance treatment with monoclonal or recombinant factor VIII concentrates in high responding inhibitor patients. Vox Sang1999; 77:65-9. 13. Kreuz W, Mentzer D, Auerswald G, Becker S, Joseph- Steiner J. Successful immunetolerance therapy of FVI- II inhibitor in children after changing from high to intermediate purity F VIII concentrate. Haemophilia 1996; 2:19. 14. Battle , et al.1999 French Immune Tolerance experience with recombinant factor VIII. Haemophilia 1999; in press. DISCUSSION 7 Immune tolerance Induction: Prospective Clinical Trials Hay C, (Manchester, UK) LENK: You told us that there is a difference in the duration of the treatment with higher doses but not in the result. I think what I have shown with the German Registry is that in those patients with between 5 and 100 BU we have a success rate of more than 90%, and so I believe there is a higher success rate. Nevertheless, in our experience there is an extremely high success rate in the between 5 and 100 BU group. HAY: The Van Kreveld data suggests that they have around an 80% success rate with unselected patients. I find it quite difficult to interpret the success rate of the Bonn Regime because the published results with respect to forty years of the Bonn Regime certainly don’t lay claim to a hundred percent success. Some of the data which regard how long some of the patients were going through tolerance are missing and that makes it impossible for me to evaluate that data using the criteria which we have been using because we made a judgement on how long we were prepared to continue with immune tolerance and as you know in most countries people are not prepared to continue forever. Using our criteria for failure the maximum time that you would be tolerized before being considered a failure would be 33 months. If you use those criteria I am not so sure that the Bonn Regime would be seen to have such a high success rate, particularly with those in whom there had been a significant interuption in treatment or who were described in the reports as undergoing prolonged treatment. We need to ask ourselves the question what is prolonged treatment and the answer is that it is a matter of judgement; one person’s prolonged treatment is interminable to another. ESCAURNA: With regard to the cost-effectiveness and the data with which we are familiar with, the low dose regime costs more as it lasts longer than the high dose regime. Do you also include the costs which arise from recombinant factor rVIIa or PPCs during that period because patients who need a longer treatment period bleed more than the other patients. In addition to the issue of cost effectiveness do you also calculate the complications which derive from those bleedings. Will you keep a record of such occurrences HAY: I think it’s extremely important that we collect that data. We’ll collect data on all concomitant hemostatic treatments, on-line infections and intercurrent bleeding because these may differ significantly. Those are the kind of safety details that will be reported to the data safety committee so that if we find that in one regime bleeding is far greater than in another we may be faced with a criterion to stop. KREUTZ: If we speak about success rates we have to understand that the definitions of success in all the studies are different. Dr.Brackman and my group in Frankfurt have other definitions of success rates. Consequently, I don’t think you can say that the success rates are the same. HAY: With regard to criteria and the data of the Van Kreveld Regime I wish to emphasize the normalization of half life and recovery. I believe that you were using the same criteria and so I think that those two studies are comparable in that respect. LAURIEN: The Germans seem very determined to continue with what they are doing. Thus it is important to start your protocol and show data to us which compares low dose to 200 once a day. We need this type of trial. HAY: We’re certainly not waiting for Germany although we would welcome their participation. The only reason that we haven’t started already is that it seemed an unsuitable time to start because of supply issues which I think are about to improve rather than being resolved. I do understand that they are now following our protocol although without the randomization which I think is very sad because even with the best will in the world I’m not entirely certain what is going to happen to that data. The way our study is designed means we can’t incorporate that data in any way because we’ve decid- Haematologica vol. 85(supplement to n. 10):October 2000
56 C.R.M. Hay ed to go for a fully randomized design rather than the original compromise of a comprehensive study. The original compromise was to permit German clinicians to participate in the study. DI MICHELE: My final comment relates to what Dr.Laurien said; I don’t think anyone is going to agree with this protocol one hundred percent. However, I do want to mention the fact that this protocol has been several years in development and I believe that I’m speaking on behalf of all the principal members of the steering committee when I say that the input from everyone, including the dissenting views, has been very important because all the critical discussion which has led to this has resulted in an end protocol that we feel very good about and that we can bring to the world with a lot of consensus. There are views that are discrepant from ours but I believe that the dissenting view has been very important in shaping this protocol. Nonetheless, as you say Dr. Laurien we will go ahead. 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
Page 5 and 6:
Haematologica 2000; 85(suppl. to n.
Page 7 and 8: 4 J.M. Lusher (range 1-34) for pati
Page 9 and 10: 6 J.M. Lusher ALEDORT: I’d just l
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 29 and 30: Haematologica 2000; 85(suppl. to n.
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 and 42: 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: 54 C.R.M. Hay Logistic barriers to
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 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
show all

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

Create successful ePaper yourself

Delete template?

Save as template?