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

70
E. Berntorp
Hemophilia A severe 4 years, 15 kg. High-responder >450
BU. Malmö protocol with continuous infusion of FVIII
(Recombinate). Attempt 1(2)
BU/FVIII:C IU/dL
900
800
700
600
500
400
300
200
100
0
0 2 4 6 8 10 12 14 16
FVIII
IVGG
CTX
Inhibitor BU
FVIII:C IU/dL
Intermittent
Day
Cont. Infusion 5.3-13.3 IU/kg/h
(127-319 IU/kg/24 h)
injection
Figure 1A. Severe hemophilia A, 4 years, 15 kg. Highresponder
>450 BU. Malmö protocol with continuous
infusion of FVIII (Recombinate). Attempt 1 (2).
Hemophilia A severe 8 years, 23 kg. High-responder >450
BU. Modified Malmö protocol (CTX replaced by
prednisone 60mg/m2/day po) (Recombinate). Attempt
2(2)
BU/FVIII:C (IU/dL)
700
600
500
400
300
200
100
0
0 2 4 6 8 10 12
IVGG x 5
Pred x 10 FVIII
Day
Inhibitor BU
FVIII:C IU/dL
Intermittent injection
Cont. Infusion 27-54 IU/kg/h
(648-1296 IU/kg/24 h)
Figure 1B. Hemophilia A severe 8 years, 23 kg. Highresponder
>450 BU. Modified Malmö protocol (CTX
replaced by prednisone 60 mg/m2/day p.o.) (Recombinate).
Results
Hemophilia A
Three hemophilia A patients were treated. In
one patient, who was a high-responder with a historical
peak above 450 BU, the first attempt was
performed using the original Malmö protocol
with cyclophosphamide but with the intermittent
injections replaced by continuous infusion (Figure
1A). The inhibitor reappeared after 6 days and
had increased to 800 BU after 2 weeks. The number
of FVIII units given was 5.3-13.3 units per kg
per hour. Four years later, this patient was treated
again but now the protocol was modified to
include prednisone instead of cyclophosphamide
(Figure 1B). The FVIII level during the first few
days was kept higher than during the first
attempt, approximating 3 IU/mL, which was
achieved by giving a continuous infusion of 27
units per kg per hour. However, the VIII:C level
dropped after only 4-5 days. The infusion was
doubled but a brisk anamnestic response was
seen, reaching a peak of around 600 BU, and
remaining at this level until day 13 of the observation
period. As in the first attempt the treatment
was discontinued, as the IT was obviously a
failure, according to previous experience with the
Malmö protocol. 5
Of the other 2 hemophilia A patients, one was
a high responder with more than 300 BU. He
was treated using protein A adsorption followed
by continuous infusion of IVgG and cyclophosphamide.
The VIII:C level went up to more than
2 IU/mL during the first days but then declined.
The inhibitor reappeared after 6 days and
peaked at 1,000 BU. The treatment was discontinued
after 8 days, as it was an obvious failure
in this case also. The number of units of FVIII
Hemophilia B severe. 5 years, 24 kg. Highresponder
>90 BU. Malmö protocol with
continuous infusion of FIX
BU/FIX:C IU/dL)
500
450
400
350
300
250
200
150
100
50
0
Protein A ads
IVGGxV
CTXxX
-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
FIX
Inhibitor BU
FIX:C IU/dL
Intermittent injedction
Day
Cont.infusion 5-13 IU/kg/h
(125-305 IU/kg/24 h)
Figure 2. Hemophilia B severe. 5 years, 24 kg. Highresponder
>90 BU. Malmö protocol with continuous
infusion of FIX.
given was 6-29 per kg per hour.
In the third patient cyclophosphamide was
replaced by prednisone. The VIII:C level was kept
very high, around 5 units per ml during the first
6 days, but the inhibitor reappeared after a week
and peaked at 70 BU on day 14, exceeding the
historical peak of 47 BU. The inhibitor declined
to a plateau of around 40 BU, and the patient
was kept on a Bonn-like regimen. He became
tolerant one year after start of treatment.
Haemophilia B
Two patients were treated as reported earlier. 6
Both patients had already been treated unsuccessfully
according to the Malmö protocol. Both
Haematologica vol. 85(supplement to n. 10):October 2000