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

More documents

Recommendations

Info

Immune Tolerance and the Treatment of Hemophilacs with an Inhibitor 65 Table 1. Control group. M/F Age at dx Underlying condition Initial bleeding res. FVIII:C Initial BIA rem. time* rem. duration** eradication treatment F 36 PSS sc., musc. hematomas 1 3200 – – CPH+st. F 66 Idipathic sc., musc. hematomas 2 610 8 36 st F 27 Post-partum Uterine 2 5.5 3 1 st. F 85 Idiopathic Hematuria 1 15 107 12 st. M 69 Idiopathic Pharyngeal 5 20 2 3 st. M 62 Idiopathic Femoral hematomas 1 437 – – CPH+st. Mean 57.5 2 714 28.25 13 *rem. time: time needed to achieve remission in weeks; **rem. duration: duration of remission (follow-up); BIA: Bethesda inhibitor assay Table 2. ITI group. Pt. M/F Age at dx Underlying condition Initial bleeding res. FVIII:C Initial BIA rem. time* rem. duration** JM M 70 Idiopathic sc., musc. hematomas 3.5 21 3 58 JT F 53 Idiopathic sc., musc. hematomas 4 20 4 21 PD F 62 Idiopathic sc., musc. hematomas 3.5 8 3 53 FR M 74 Gastric cc. sc., musc. hematomas 1.4 19 2 20 Gy.Sz M 55 Renal cc.+IFNα tx Retroperitoneal 5 320 10 24 PF M 79 Gastric cc. Retroperitoneal 4 22 10 36 LL M 65 Idiopathic sc., musc. hematomas 2 30 3 35 EB M 58 Psoriasis Pharyngeal 1 60 3 43 IJ F 6ç Psoriasis Retroperitoneal 1 1128 – – JB F 49 Idiopathic+MGUS Retroperitoneal 7 64 12 15 KL F 75 Idiopathic Femoral hematoma 14 28 3 25 MK F 60 PSS Brachial hematoma 16 10.3 2 18 JA F 57 Idiopathic CNS, intra-abdominal 9 6 4 7 AP M 74 Idiopathic Femoral hematoma 2 58 5 3 Mean 64 5.2 128.2 4.6 25.6 *rem. time: time needed to achieve remission in weeks; **rem. duration: duration of remission (follow-up); BIA; Bethesda inhibitor assay viduals presenting with acquired hemophilia and severe hemorrhage need rapid and effective treatment. On the basis of some earlier experience with synchronization of plasma exchange therapy of various autoimmune disorders, 4,5 and some limited experience with the combined administration of factor VIII and immunosuppressive treatment, 6-8 we have developed a new aggressive protocol for the treatment of patients with acquired factor VIII antibody. Design and Methods We evaluated the results of 14 consecutive non-hemophiliac patients with factor VIII inhibitor treated in a single center with our ITI protocol between 1992 and 1999, comparing them to 6 historical control patients treated with the traditional immunosuppressive therapy (steroid ± cyclophosphamide) between 1988 and 1992 in the same setting. The treatment of acute bleeding episodes was not different (PCC, FEIBA, porcine and human FVIII concentrates, plasmapheresis and transfusions) in the two study groups. Our ITI protocol consists of 3 weeks of treatment with: I. human FVIII, 1st week: 30 U/kg/day, 2nd week: 20 U/kg/day, 3rd week: 15 U/kg/day, and II. cyclophosphamide 200 mg/day to a total dose of 2-3 grams, and III.methylprednisolone 1st week: 100 mg/day intravenously; 2-3rd week: tapering of the dose gradually. I/II. were immediately discontinued if FVIII:C normalized within the 3 weeks of treatment. After the disappearance of the inhibitor no further maintenance immunosuppression was given. High purity (Beriate-P, Hemoctin SDH, Koate- HP) and ultra-high purity (Octonativ-M, Hemofil- M) FVIII concentrates were used for the ITI. We performed aPTT and mixing tests before and after Haematologica vol. 85(supplement to n. 10):October 2000
66 L. Nemes et al. Figure 1. A giant life-threatening dorsal hematoma causing severe anemia in patient #1 of the control group. Figure 3. Subcutaneous brachial haematoma in patient #7 of the ITI group. times a week. The definition of success was the disappearance of the inhibitor in the Bethesda assay system and the persistent normalization of the FVIII:C value (i.e. >70% activity of the normal). The characteristics of the control and the ITI groups are demonstrated in Tables 1 and 2. The sex ratio, mean age at diagnosis, the initial and peak inhibitor titers and residual FVIII:C values were similar in the two groups. Table 3. A summary of the patients’ mean values. Figure 2 (left). Extensive subcutaneous hematomas in patient #4 of the ITI group. Figure 5 (right). Gross intra-abdominal and retroperitoneal hematoma causing a life-threatening condition in patient #6 of the ITI group. Figure 4. Subcutaneous and retroperitoneal hematoma in patient #5 of the ITI group. two hours of incubation, Bethesda inhibitor assay, porcine FVIII cross-reactivity, FVIII:C before and after FVIII administration (recovery), three Female/Male 11 9 Age at diagnosis: 62 years (27-85 years) Residual FVIII:C: 4.3% (1-16%) Initial human inhibitor titer: 304.6 BU (5.5-3,200 BU) Peak human inhibitor titer: 356.5 BU (8-3,200 BU) (maximal value after FVIII challenge) Initial porcine cross-reactivity: 12.4 IU/mL (0-104 IU/mL) (measured in 11 patients) Peak porcine cross-reactivity: 12.65 IU/mL (0-104 IU/mL) (measured in 11 patients) Some typical bleeding manifestations are shown in Figures 1 to 5. Results Typical courses of the ITI therapy are shown in Figures 6 and 7. Eradication of the inhibitor occurred in 13/14 patients in the ITI group versus 4/6 patients in the control group. The comparison of the control and ITI groups is shown in Table 4. The main difference between the two groups was in the time needed for complete disappearance of the inhibitor (4.6 weeks for ITI vs. 28.3 weeks for controls). In the ITI group we have observed only two relapses during the relatively long mean follow-up period (25.6 months), and in both cases the same re-induction protocol was successful again. No bleeding-related mortality occurred in the ITI group in contrast to that of 33% in the controls. Apart from the well-known adverse 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 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 67: Haematologica 2000; 85(suppl. to n.
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 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?