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Tolerance induction using the Malmo treatment model 1982-1995

Freiburghaus, Christian LU ; Berntorp, Erik LU ; Ekman, Maj LU ; Gunnarsson, Margoth LU ; Kjellberg, B and Nilsson, I M (1999) In Haemophilia 5(1). p.32-39
Abstract
The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmo centre regarding tolerance induction according to the Malmo Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been... (More)
The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmo centre regarding tolerance induction according to the Malmo Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been made to induce tolerance. Ten of the 16 haemophilia A (62.5%) and 6/7 patients with haemophilia B (86%) became tolerant after the treatment. The chances of success or failure are roughly equal, if the series is considered in a historical perspective. The data showed that the chances of success in tolerance induction with the Malmo protocol were best in those patients with low inhibitor titres, with relatively low historical inhibitory peak and with a long interval since the previous replacement therapy. This was especially true where no inflammatory state was present at the start or during tolerance induction. The advantage with this method compared to the high-dose regimen is that in the successful cases tolerance can be achieved within 3-4 weeks. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factor IX, factor VIII, haemophilia, inhibitors, tolerance induction
in
Haemophilia
volume
5
issue
1
pages
32 - 39
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:10215945
  • scopus:0033041458
ISSN
1351-8216
DOI
10.1046/j.1365-2516.1999.00195.x
language
English
LU publication?
yes
id
5c5cc7a4-31e6-40e8-889f-4a42c774fcf3 (old id 1115052)
date added to LUP
2008-07-07 13:08:51
date last changed
2017-03-05 03:24:19
@article{5c5cc7a4-31e6-40e8-889f-4a42c774fcf3,
  abstract     = {The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmo centre regarding tolerance induction according to the Malmo Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been made to induce tolerance. Ten of the 16 haemophilia A (62.5%) and 6/7 patients with haemophilia B (86%) became tolerant after the treatment. The chances of success or failure are roughly equal, if the series is considered in a historical perspective. The data showed that the chances of success in tolerance induction with the Malmo protocol were best in those patients with low inhibitor titres, with relatively low historical inhibitory peak and with a long interval since the previous replacement therapy. This was especially true where no inflammatory state was present at the start or during tolerance induction. The advantage with this method compared to the high-dose regimen is that in the successful cases tolerance can be achieved within 3-4 weeks.},
  author       = {Freiburghaus, Christian and Berntorp, Erik and Ekman, Maj and Gunnarsson, Margoth and Kjellberg, B and Nilsson, I M},
  issn         = {1351-8216},
  keyword      = {factor IX,factor VIII,haemophilia,inhibitors,tolerance induction},
  language     = {eng},
  number       = {1},
  pages        = {32--39},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Tolerance induction using the Malmo treatment model 1982-1995},
  url          = {http://dx.doi.org/10.1046/j.1365-2516.1999.00195.x},
  volume       = {5},
  year         = {1999},
}