Successful long-time treatment with mycophenolate-mofetil in a child with acquired factor VIII inhibitor.

UNLABELLED: Here, we report about a boy (age: 18 years) who developed an acquired factor VIII inhibitor at the age of 9 years. He presented with bleeding in his right ankle, multiple haematomas and a high-titer factor VIII type II inhibitor (400 BU). THERAPY: He received treatment with MMF (CellCept®), dexamethasone-immunoglobulin pulses, and rituximab together with high dose FVIII (Hannover protocol). His inhibitor titer decreased rapidly, and half-life and recovery normalized. Inhibitor titres increased after reduction of the factor VIII dose, and increased further after MMF was stopped. A second treatment course with MMF again resulted in reduction of the titre, improvement in half life and recovery, and no more bleedings. Inhibitor reappeared with MMF dose reduction, again accompanied by severe bleeding. Additional rituximab stopped the bleedings, and treatment with MMF has been continued since. CONCLUSION: Although the laboratory parameters showed no complete remission, severe bleedings and expensive factor replacement could be avoided by long-term treatment with MMF.

[Regional coordination of paediatric oncological care in northwestern Lower Saxony, Germany--network funded by health insurance companies]. / Verbund PädOnko Weser-Ems--Regionale ambulante Versorgung pädiatrisch-onkologischer Patienten aus der Weser-Ems-Region im Rahmen einer Integrierten Versorgung.

The cure rates in pediatric oncology have been substantially improved due to standardized treatment strategies and centralization of therapy. Close clinical and hematological monitoring is mandatory for patients between periods of chemotherapy for early detection and treatment of therapy-related complications such as infections. This results in frequent and time-consuming outpatient examinations for the patient and family at the oncological center in order to evaluate clinical condition and hematological findings. In widespread regions such as the Weser-Ems area in northwest Lower Saxony, Germany, the long distances between patients' home and the oncological center lead to higher risks and impairment of quality of life (QoL) for the patients and their families. Accordingly, in 2001 pediatric hospitals and practices, patient care services and patients' support groups in Weser-Ems founded a network (Verbund PädOnko Weser-Ems). The "Verbund PädOnko" aims at coordinated, high-quality regional outpatient patient treatment in order to reduce risks of long-distance transports to reach the oncological center. Since 2005 a newly established mobile care team realized 1 443 home visits covering a total of 150 300 km. Since 2007 the network has been funded by health insurance organisations. Internal and external benchmarking was performed showing that the rate of short term inpatient treatments were reduced. Treatment quality was assured and the QoL of the patients and their families was improved through the work of the network. The "Verbund PädOnko Weser-Ems" network represents a promising prototype model for the regional coordination of outpatient treatment and care of patients with rare diseases in wide spread areas.

[Inhibitor development after early high exposure and cerebral haemorrhage. Costs and factor demand for a successful immunotolerance induction therapy]. / Inhibitorentwicklung nach früher hoher Exposition und Hirnblutung. Kosten einer erfolgreichen Immuntoleranztherapie.

Severe haemophilia A was diagnosed postpartum in a newborn. The mother was known as a conductor (intron 22 inversion) and an uncle had a persistently high titer inhibitor after failed ITI. Due to a cephalhaematoma, a high-dose pdFVIII substitution was given within the first days after birth. At the age of six month a severe cerebral haemorrhage occurred, making a high-dose pdFVIII substitution and neurosurgical intervention necessary. Several days later a porth-a-cath-system was implanted. The development of a high titer inhibitor occured six days later, an ITI was started according to the Bonn Protocol. Initially rFVIIa was given in addition to the pdFVIII substitution. Seven days after the beginning of treatment the inhibitor was no longer detectable. At monthly intervals the FVIII dosage was reduced until the dosage complied with a prophylaxis in severe haemophilia A. The duration of the ITI was nine months. A total of 30 mg rFVIIa and 276000 IU pdFVIII were used; costs in total: 280173.60 Euro.

Inhibitor-Immunology-Study. Different HLA-types seem to be involved in the inhibitor development in haemophilia A.

UNLABELLED: The development of inhibitors is one of the most important complications of replacement therapy in haemophilia, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors. Cytokines and their receptors, T-cell receptors, and the Major Histocompatibility Complex may play important roles in the development of inhibitors. Earlier studies showed non significant associations between HLA class and inhibitor development. Later studies found an increased risk of inhibitor development if there was a combination between certain factor VIII mutations and HLA antigens. We performed HLA typing in 50 patients with haemophilia A in an effort to find associations with inhibitor development. RESULTS: 25 patients had developed an inhibitor (11 low titre, 14 high titre), and 25 never had. In logistic regression analysis, HLA-A 34, DRB1 0405, DRB1 1301 seemed to be involved in inhibitor development and HLA-A 30, B 13, B15, B 57, Cw 12, DQB1 0303, DPB1 0201 protection against inhibitor development. In our patients, the HLA-associations with inhibitor development were different from those in previous publications.