322.

DISORDERS OF COAGULATION OR FIBRINOLYSIS | NOVEMBER 13, 2019

Low-Dose Immune Tolerance Induction for Hemophilia

a Children with Poor-Risk High-Titer Inhibitors
*,1 *,2 *,2 *,2
Zekun Li, MBBS, Zhenping Chen, PhDMD, Xiaoling Cheng, Xinyi Wu,
*,2 *,2 *,2 3,4 *,2
Li Gang, Zhen Yingzi, Cai Siyu, Man-Chiu Poon, Runhui Wu, MD PhD
1
Beijing Children's hospital, Capital Medical University, Beijing, China
2
Beijing Children's Hospital, Capital Medical University, Beijing, China
3
Department of Medicine, Pediatrics and Oncology, and Southern Alberta Rare Blood and
Bleeding Disorders Comprehensive Care Program, University of Calgary, Calgary, Canada
4
University of Calgary Cumming School of Medicine, Alberta, Canada

bloodjournal Blood blood (2019) 134 (Supplement_1) : 1122.

http://doi.org/10.1182/blood-2019-132021

Background:

Low-dose immune tolerance induction (ITI) +/- immunosuppression as a practical ITI strategy in China
showed a relatively satisfactory success rate and economic advantages in pilot study. However, the
outcome still needs to be verified by larger cohort.

Aim:

To report the efficacy of this low-dose ITI +/- immunosuppression strategy in hemophilia A children ≥ 10
BU.

Methods:

This was a single center, prospective study in 53 hemophilia A subjects from Sep 2016 to Apr 2019. All

subjects having ≥ 10 BU receiving ~50IU/kg FVIII every other day using domestic intermediate purity
pdFVIII/VWF products, either alone or in combination with rituximab and prednisone judging by inhibitors
and ITI response.

Results:
Finally, 46 subjects received this strategy at a median of 3.2 (IQR, 2.3-6.5) years old, their pre-ITI inhibitor
titer was median 30.0 (range, 10.1-416) BU. Analysis at median 15.1 (range 3.0-34.4) months follow-
up, success (inhibitor <0.6BU) was achieved in 32 (69.6%) subjects, partial success (inhibitor <5BU but
>0.6BU) in 11 (23.9%) subjects, and failure in 5 (10.9%) subjects. Between subjects administered ITI-
alone and ITI- immunosuppression, no significant difference was observed in time to success (median
8.5; IQR 6.7-11.7 vs 10.2; IQR 5.1-25.1, P=0.164). The mean monthly bleeding rate on ITI was 0.49
which declined 59.3% compared with pre-ITI period. Subjects administered ITI-immunosuppression
(0.54 ± 0.46) was higher than ITI-alone (0.42 ± 0.69) although with no significantly difference (P=0.089).
Seven (21.9%) subjects experienced inhibitor recurrence, 4 subjects treated with ITI-alone, 3 with ITI-
immunosuppression. Recurrence occurred at a median of 4.8 (range, 2.8-10.8) months after successful
ITI with inhibitor titer transiently rising to median 0.7 (range, 0.7-1.5) BU.

Conclusion:

This low-dose ITI +/- immunosuppression therapy in subjects with pre-ITI inhibitor ≥ 10 BU showed a
success rate similar to other high/intermediate-dose regimen for the whole inhibitor patients. The subjects
treated with ITI-immunosuppression did not showed higher recurrence at present, while a longer time
follow-up is still needed.

Disclosures
Poon: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees;
Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioverativ/
Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; World
Federation of Hemophilia: Other: Not-for-profit organization affiliation: volunteer ; Novo Nordisk:
Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Participation
in sponsored research; CSL-Behring: Consultancy, Membership on an entity's Board of Directors or
advisory committees, Other: Grant Funding; Bayer: Consultancy, Membership on an entity's Board of
Directors or advisory committees, Other: Grant Funding; Takeda/Shire: Consultancy, Membership on an
entity's Board of Directors or advisory committees; Octapharma: Consultancy, Membership on an entity's
Board of Directors or advisory committees.

Author notes
*Asterisk with author names denotes non-ASH members.

© 2019 by the American Society of Hematology