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Background: Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI. Estimating the individual chance of ITI success allows clinicians, patients, and their families to support shared decision-making. Objectives: We aimed to identify clinical predictors of ITI success and to develop a clinical prediction model to estimate the chance of successful ITI in persons with severe HA. Methods: This multicenter study included persons with severe HA who received ITI. Clinical data were collected. Successful ITI was defined by a negative inhibitor titer and an adequate response to FVIII concentrates. A multivariable logistic regression model was developed. Model performance and internal validation were performed. Results: Of 206 participants with a median age of 19.8 months (IQR, 12.1-38.8) at ITI start, 148 (71.8%) achieved ITI success. Our clinical prediction model included 4 predictors of ITI success: cumulative number of FVIII exposure days at inhibitor development, peak inhibitor titer, ethnicity, and F8 mutation type. The C statistic was 0.801 (95% CI, 0.70-0.87). Conclusion: In our study, including 206 people with severe HA and inhibitors, we developed a clinical prediction model to estimate the chance of successful ITI. After future external validation, this clinical prediction model may be useful for informing clinicians and families.

Abstract The corneomandibular reflex was first described in 1902 by German doctor Von Sölder, who reported the presence of the reflex in patients and in the general population. For him, the corneomandibular reflex represented an exaggeration of the normal response. This was one of the more than 250 reflexes described in the beginning of the 20th century, during the so called "race of the reflexes".

Fanconi anaemia (FA) is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. Treatment of these complications with radiation and alkylating agents may enhance chromosomal breakage. We have evaluated the effect of amifostine (AMF) on basal and mitomycin C (MMC)-induced chromosomal breakage in FA blood cells using the micronucleus assay. The basal micronuclei count was higher among FA patients than healthy subjects. Pre-treatment with AMF significantly inhibited micronucleation induced by MMC in healthy subjects (23.4 ± 4.0 – MMC vs 12.3 ± 2.9 – AMF →MMC) MN/1000CB, p < 0.01, one way ANOVA) as well as in FA patients (80.0 ± 5.8 – MMC vs 40.1 ± 5.8 – AMF →MMC) MN/1000CB, p < 0.01, ANOVA). Release of ROS by peripheral blood mononuclear cells treated with AMF →MMC and measured by chemoluminometry showed that AMF-protection was statistically higher among FA patients than in healthy individuals. Based on these results we suggest that AMF prevents chromosomal breakage induced by MMC, probably by its antioxidant effect.