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

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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