Abstract
Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/ factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure. Patients with severe or moderate haemophilia A and high responding inhibitors who had at least one poor prognostic factor for ITI failure were prospectively followed-up. Success was defined by undetectable inhibitor, recovery and half life >66% of expected values. ITI dose regimens were chosen by each haemophilia centre. Seventeen haemophiliacs (16 severe, one moderate), aged 4-54 years (median 23) were followed-up for 6-71 months. Poor prognostic factors were delayed-onset ITI (n = 16), age >6 years (n = 16), previously failed ITI (n = 4), inhibitor peak >200 BU (n = 2) and inhibitor >10 BU when ITI was started (n = 4). Complete success was obtained in nine patients (53%) after 4-30 months of treatment (median 24), including two of four patients who had previously failed ITI. Seven patients achieved a partial success, with sustained low inhibitor titres (median 1.5 BU, range 1.1-2.8) but abnormal recovery and/or half-life, while the remaining patient withdrew ITI after 12 months when the inhibitor titer was still 70 BU. These findings suggest that high purity VWF/FVIII complex concentrates are effective in ITI, even in patients at high risk of failure.
| Original language | English |
|---|---|
| Pages (from-to) | 373-379 |
| Number of pages | 7 |
| Journal | Haemophilia |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jul 2007 |
Fingerprint
Keywords
- Haemophilia A
- Immune tolerance
- Inhibitors
- Rescue treatment
- VWF
ASJC Scopus subject areas
- Hematology
Cite this
Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. / Gringeri, Alessandro; Musso, R.; Mazzucconi, M. G.; Piseddu, G.; Schiavoni, M.; Pignoloni, P.; Mannucci, P. M.; Bernasconi, S.; Brito, D.; Castaman, G.; Coppola, A.; Di Minno, G.; Gamba, G.; Iannaccaro, P. G.; Landolfi, R.; Perja, M. Muça; Prieto, M.; Santagostino, E.; Schinco, P. C.; Villar, A.
In: Haemophilia, Vol. 13, No. 4, 07.2007, p. 373-379.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response
AU - Gringeri, Alessandro
AU - Musso, R.
AU - Mazzucconi, M. G.
AU - Piseddu, G.
AU - Schiavoni, M.
AU - Pignoloni, P.
AU - Mannucci, P. M.
AU - Bernasconi, S.
AU - Brito, D.
AU - Castaman, G.
AU - Coppola, A.
AU - Di Minno, G.
AU - Gamba, G.
AU - Iannaccaro, P. G.
AU - Landolfi, R.
AU - Perja, M. Muça
AU - Prieto, M.
AU - Santagostino, E.
AU - Schinco, P. C.
AU - Villar, A.
PY - 2007/7
Y1 - 2007/7
N2 - Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/ factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure. Patients with severe or moderate haemophilia A and high responding inhibitors who had at least one poor prognostic factor for ITI failure were prospectively followed-up. Success was defined by undetectable inhibitor, recovery and half life >66% of expected values. ITI dose regimens were chosen by each haemophilia centre. Seventeen haemophiliacs (16 severe, one moderate), aged 4-54 years (median 23) were followed-up for 6-71 months. Poor prognostic factors were delayed-onset ITI (n = 16), age >6 years (n = 16), previously failed ITI (n = 4), inhibitor peak >200 BU (n = 2) and inhibitor >10 BU when ITI was started (n = 4). Complete success was obtained in nine patients (53%) after 4-30 months of treatment (median 24), including two of four patients who had previously failed ITI. Seven patients achieved a partial success, with sustained low inhibitor titres (median 1.5 BU, range 1.1-2.8) but abnormal recovery and/or half-life, while the remaining patient withdrew ITI after 12 months when the inhibitor titer was still 70 BU. These findings suggest that high purity VWF/FVIII complex concentrates are effective in ITI, even in patients at high risk of failure.
AB - Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/ factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure. Patients with severe or moderate haemophilia A and high responding inhibitors who had at least one poor prognostic factor for ITI failure were prospectively followed-up. Success was defined by undetectable inhibitor, recovery and half life >66% of expected values. ITI dose regimens were chosen by each haemophilia centre. Seventeen haemophiliacs (16 severe, one moderate), aged 4-54 years (median 23) were followed-up for 6-71 months. Poor prognostic factors were delayed-onset ITI (n = 16), age >6 years (n = 16), previously failed ITI (n = 4), inhibitor peak >200 BU (n = 2) and inhibitor >10 BU when ITI was started (n = 4). Complete success was obtained in nine patients (53%) after 4-30 months of treatment (median 24), including two of four patients who had previously failed ITI. Seven patients achieved a partial success, with sustained low inhibitor titres (median 1.5 BU, range 1.1-2.8) but abnormal recovery and/or half-life, while the remaining patient withdrew ITI after 12 months when the inhibitor titer was still 70 BU. These findings suggest that high purity VWF/FVIII complex concentrates are effective in ITI, even in patients at high risk of failure.
KW - Haemophilia A
KW - Immune tolerance
KW - Inhibitors
KW - Rescue treatment
KW - VWF
UR - http://www.scopus.com/inward/record.url?scp=34447287337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34447287337&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2516.2007.01484.x
DO - 10.1111/j.1365-2516.2007.01484.x
M3 - Article
C2 - 17610550
AN - SCOPUS:34447287337
VL - 13
SP - 373
EP - 379
JO - Haemophilia
JF - Haemophilia
SN - 1351-8216
IS - 4
ER -