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Low-dose Immune Tolerance Induction in Hemophilia

A Single-Center Experience

Zulfikar, Bulent MD; Koc, Basak MD; Ozdemir, Nihal MD

Journal of Pediatric Hematology/Oncology: August 2019 - Volume 41 - Issue 6 - p e355–e358
doi: 10.1097/MPH.0000000000001391
Online Articles: Original Articles

Introduction: The development of inhibitors against factors VIII/IX is the most serious complication in hemophilia. The best treatment strategy for inhibitor eradication is immune tolerance induction (ITI). The aim of this study was to evaluate patients treated with low-dose ITI at a single center with limited resources.

Materials and Methods: In total, 29 (8.05%) of 360 hemophilia A patients exhibited inhibitors. The data from hemophilia patients with inhibitors undergoing ITI between 1999 and 2017 were collected and analyzed.

Results: Seventeen ITIs administered to 15 hemophilia A patients with inhibitors were analyzed, and the data from 13 ITIs conducted in 12 patients were evaluated. The median age at ITI onset was 10 years (range: 1.25 to 52 y). The maximum inhibitor titer before ITI was 30 Bethesda Units (BU) (range: 4.48 to 135), and the median inhibitor titer was 1.25 BU (range: 0 to 5.6) at the onset of ITI. The median time interval between the inhibitor development and ITI onset was 60 months (range: 7 to 264 mo). The median inhibitor titer during ITI was 3.4 BU (range: 0 to 158.7). At the end of the treatment, 4 of the 12 patients (33.3%) exhibited a complete response, 4 (33.3%) had partial responses (with continuing ITI), and 4 (33.3%) exhibited ITI failure.

Conclusions: Treatment of hemophilia patients with inhibitors is challenging, and ITI is the best treatment method; however, a high-dose daily ITI regimen cannot be given to every patient in every country due to its high cost. Our results show that low-dose ITI may be a choice for selected patients with inhibitors.

Department of Pediatric Hematology and Oncology, Cerrahpasa Medical Faculty and Oncology Institute, Istanbul University, Istanbul, Turkey

B.Z. has received research fund from Pfizer.

B.Z. is on advisory board for Pfizer, Shire, Novo Nordisk, Sobi and consultant for Roche. The remaining authors declare no conflict of interest.

Reprints: Basak Koc, MD, Oncology Institute, Istanbul University, Capa Kampüsü 34093, Istanbul, Turkey (e-mail:

Received September 12, 2018

Accepted November 25, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.