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

Haematologica 2000; 85(suppl. to n.10)
p. 40-44
Registries of
Immunotolerance Protocol
The Maintenence of Tolerance after Successful Immune Tolerance
Induction in Hemophilia A and B: The North American Registry
D. DIMICHELE, B. KRONER AND THE FACTOR VIII / IX SUBCOMMITTEE OF THE INTERNATIONAL SOCIETY FOR
THROMBOSIS AND HEMOSTASIS
Cornell and the Research Triangle Institute, New York, NY and Rockville, MD, USA
Abstract
The North American Immune Tolerance Registry
(NAITR) was initiated with the goal of determining,
by questionnaire, immune tolerance (ITT) practices
in hemophilia treatment centers in Canada and the
United States. Sixty-eight centers (40%) responded.
Of the 130 registry subjects with hemophilia A who
completed ITT, 93 (72%) achieved tolerance. Of the
11 completed ITT courses in patients with hemophilia
B, 4 (36%) were successful. Maintenance therapy
was defined as any clotting factor regimen
administered subsequent to the patient achieving
the treating physician's criteria for successful
immune tolerance. Seventy-five (81%) of 93 individuals
in the hemophilia A cohort who successfully
achieved tolerance were maintained on a regular
(prophylactic factor VIII (FVIII) regimen for a variable
time period post-ITT. The median dose used
was 150 units/kg/week (range: 17-700). Forty-eight
(64%) subjects remained tolerant while receiving
regular doses of FVIII for a median observation period
of 13 months (range 0-129 months). Of 27
patients whose maintenance therapy had been
stopped, 17 (68%) remained tolerant over a median
period of 19 months (range 1-54 months) and 9
relapsed. Among the relapses, 3 occurred after
maintenance therapy was stopped; 6 were noted on
prophylactic FVIII at a median time of 11 months
(range 2-61 months). The definition of tolerance was
reviewed for the 9 subjects who relapsed and was
defined by a normal recovery and survival in only
1/9 patients. Among the 11 hemophilia B subjects
in the cohort who completed tolerance, 4 had a successful
outcome. Four individuals were placed on
maintenance regimens of 25-100 units FIX/kg/day
and all remained tolerant.
©2000, Ferrata Storti Foundation
Key Words: hemophilia A, hemophilia B, immune tolerance,
inhibitors
Correspondence: Donna DiMichele, MD, New York Presbyterian
Hospital - Cornell University, 525 East 68th Street, Room P-695, New
York, NY 10021 - Phone: international +212-746-3418 - Fax: international
+212-746-8986 - E-mail: dmdimich@mail.med.cornell.edu
The North American Immune Tolerance Registry
(NAITR) was a project of the ISTH Factor
VIII/IX Subcommittee conceived in 1992
by Dr. Carol Kasper. The NAITR was initiated
with the goal of further determining immune
tolerance (ITT) practices in Canada and the
United States with respect to the identification
of 1) therapeutic regimens in use; 2) therapeutic
outcomes; 3) predictors of successful outcome,
4) complications of therapy and 5) the
maintenance of successful tolerance over time.
We now report the data accumulated from the
NAITR between March 1993 and August 1997
with respect to maintenance of tolerance after
successful induction in hemophilia A and B
inhibitor patients.
Design and Methods
Data collection
Data collection forms were initially sent in
March 1993 to 168 hemophilia treatment centers
(HTCs) in the United States (US) and Canada.
Data updates were requested from participating
HTCs in March 1994 and April 1996. The
last update on the data set was performed in
August 1997 to include several additional participating
centers. Data forms were completed
by the HTC medical directors or hemophilia
nursing staff. The collection tool was intended to
study the following parameters: 1) the frequency
of past and current use of ITT among hemophilia
A and B patients with inhibitors; 2) the
therapeutic regimens in use including treatment
product purity, dosing and duration of therapy;
3) the clinical outcome (success or failure) relative
to the following aspects of treatment: a)
duration of ITT; b) interval between inhibitor
diagnosis and initiation of ITT; c) age at ITT
induction; d) HIV status; e) race; f) and inhibitor
titers including i) historical pre-ITT peak; ii) titer
immediately prior to ITT induction (pre-induction
titer) and iii) peak titer on ITT. Data were
also collected on dosing and product regimens
Haematologica vol. 85(supplement to n. 10):October 2000