Our results suggest that the chosen antiangiogenic drug combination is particularly beneficial for patients with MB and warrants further investigation.

Dasatinib is considered an effective drug in imatinib-resistant chronic myeloid leukemia. Although reported to be well-tolerated, severe events such as pleural or pericardial effusion have been reported at 140 mg daily. We examined our chronic myeloid leukemia patients treated with dasatinib at 100 mg or 50 mg daily and identified 4 of 13 patients who developed marked effusion formation. In 2 patients, grade III/IV pleural and/or pericardial effusions were recorded. All 4 patients had received previous anti-leukemia therapy but none had preexisting cardiac or pulmonary diseases. In 3 patients, dasatinib had to be discontinued despite treatment with diuretics and glucocorticosteroids. In conclusion, dasatinib-treated chronic myeloid leukemia patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at 100 mg or 50 mg daily. Therefore, all patients should be examined for pre-existing comorbidity and risk factors before starting dasatinib and all should have repeated chest Xrays during long-term dasatinib therapy.

Neuroendocrine tumors (NETs) are rare neoplasms predominantly arising in the gastrointestinal-tract or the lungs of adults. To date, only ten cases of primary central nervous system (CNS) NETs have been reported, with just three of them describing a neuroendocrine carcinoma (NECA) and none occurring in a child. We report on a previously healthy 5-year-old boy, who presented with headaches, nausea and vomiting, and was diagnosed with a left cerebellar solid mass with a cystic component. After gross-total resection, histology revealed a neuroendocrine carcinoma. Molecular analysis of the tumor tissue showed a KRAS-splice-site mutation (c451-3C > T). The KRAS-mutation was discovered to be a maternal germline mutation, previously described as likely benign. After extensive search for an extracranial primary tumor, including Ga-68 DOTANOC-PET-CT, the diagnosis of a primary CNS NECA was established, and proton irradiation was performed. Unfortunately, the patient developed an in-field recurrence just 5 weeks after the end of radiotherapy. The tumor was re-resected with vital tumor tissue. Six cycles of chemotherapy were initiated, consisting of cisplatin, carboplatin, etoposide and ifosfamide. The patient remains disease free 22 months after the end of treatment, supporting the beneficial effect of platinum- and etoposide-based chemotherapy for this tumor entity.

4496 The multikinase BCR/ABL inhibitor dasatinib exerts major growth-inhibitory effects in imatinib-resistant patients with chronic myeloid leukemia (CML). Although previously reported to be a well-tolerated drug, several side effects such as pleural and pericardial effusion have been reported at a dose of 140 mg daily. Therefore, the approved standard dose of dasatinib was reduced to 100 mg daily. More recent data suggest that freshly diagnosed patients with CML treated with dasatinib at 100 mg once daily may still develop pleural effusions, but the frequency of this side effect was reported to be lower compared to patients receiving 140 mg daily dasatinib. Moreover, effusion formation was reported to be less severe, with almost no grade 3/4 events, in patients receiving 100 mg daily dasatinib. We examined a cohort of CML patients (n=13) treated with dasatinib at 100 mg or 50 mg daily, for development of severe non-hematologic side effects. Patients received dasatinib for at least 3 months (range: 3–38 months; observation period: March 2005 to June 2010). Of these 13 patients, 4 had previously received 140 mg dasatinib daily. In all 4 patients, the dose of dasatinib was reduced to 100 mg or 50 mg daily because of effusion formation. In the other 9 patients, the initial dose of dasatinib was 100 mg daily. Of these 9 patients, 2 patients in chronic phase (CP) received dasatinib as frontline therapy. Four of our 13 patients developed severe effusions (grade 3/4) while on dasatinib at 100 mg or 50 mg daily, including one CP patient receiving dasatinib as frontline therapy. In two patients, massive pleural effusions were recorded, and two developed pericardial effusion together with pleural effusions. In two patients, effusion formation required paracentesis and surgical intervention. No pre-existing cardiac or pulmonary diseases were known in these 4 patients. In 3 patients, dasatinib had to be discontinued despite treatment with low dose glucocorticosteroids and diuretics. After switching to an alternative BCR/ABL inhibitor, no further effusion formation occurred. In summary, dasatinib-treated patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at a dose of 100 mg or 50 mg daily. Therefore, all patients should be examined carefully for pre-existing relevant comorbidities and cardiovascular risk factors before dasatinib is started, and all patients should have repeated chest × ray controls during long-term treatment with dasatinib. Disclosures: Valent: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

Headaches in children are a common, but unspecific symptom that can have many underlying causes, ranging from unspecific tension headache through migraine and up to encephalitis and intracranial hypertension. We present the case of a 14-year-old boy who presented to our emergency department with headache, nausea as well as vomiting and developed seizures later on. The initial diagnosis was complicated by a magnetic resonance imaging which did not show any signs of inflammation, but was of limited informative value due to orthodontic appliances. Despite the unremarkable imaging, prophylactic antiviral and antibiotic treatment was started after lumbar puncture. Herpes simplex virus as well as human herpes virus 7 were confirmed in the cerebrospinal fluid. Although both viruses are ubiquitous, severe infections are a rare complication. Immunodeficiency syndromes are predisposing factors for serious complications and genetic analysis of UNC93B and TLR-3 might be helpful for decision-making. No genetic or immunologic predisposition was found in our patient. The patient’s condition deteriorated rapidly, so he had to be admitted to the pediatric intensive care unit, where he was intubated and his antiviral treatment with acyclovir was extended by foscarnet. After prolonged mechanical ventilation, he slowly improved. With intensive neurorehabilitation, he could finally return to his daily life activities 3 months after diagnosis. Despite headaches being an unspecific symptom, the possibility of a herpes simplex virus encephalitis should always kept in mind, especially in patients presenting with additional symptoms such as vomiting, altered mental status and/or focal neurological deficits. An initial magnetic resonance imaging might be misleading if orthodontic appliances are in place. Initiation of treatment without delay is crucial for neurologic outcome of herpes simplex virus encephalitis.