Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
ROHHAD (rapid onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic
 dysregulation) syndrome is a rare pediatric disorder associated with a cancer called
 neuroblastoma and presumed to be driven by an attack of the immune system on specific area in
 the brain. Patients develop severe symptoms and often succumb to this disease. Based on the
 researchers' experience the investigators conduct a clinical trial to study intensive
 immunosuppression with high-dose cyclophosphamide in these patients. In addition to
 describing the symptomatic improvement, the investigators' trial seeks to define objective
 markers of disease activity.
Baseline evaluation will include:

 Sleep study and pulmonary evaluation Hormone levels Determination of up to 6 key
 ROHHAD-related symptoms to be followed Hyperphagia questionnaire
 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) positron emission tomography (PET)
 scan Dual energy x-ray absorptiometry (DXA) scan Cerebrospinal fluid (CSF) analysis

 Patients will be treated with cyclophosphamide, 50 mg/kg (ideal body weight)/dose daily for 4
 days, with Mesna and hydration as prophylaxis against hemorrhagic cystitis. Supportive care
 will include mucosal care, transfusions, infection prophylaxis, and empiric treatment for
 febrile neutropenia.

 Composite severity score will be assessed to measure response of key symptoms, and formal
 neuropsychological testing, sleep study, and hormone studies will be performed.
Inclusion Criteria:

 -  Diagnosis of ROHHAD syndrome confirmed by two physicians.

 -  Any symptomatic improvement in response to a course of rituximab (five weekly doses)
 as assessed by parents and/or treating physician

 -  Normal brain MRI

 -  Cared for at home by the family

 -  Patients requiring bilevel positive airway pressure (BiPAP) support are eligible

 -  Negative pregnancy test for post pubertal female patients

 Exclusion Criteria:

 -  Cardiac ejection fraction <40% or shortening fraction <20%.

 -  Inadequate pulmonary function, i.e. forced vital capacity or forced expiratory volume
 at one second < 50% of predicted for children greater than 8 years of age, or oxygen
 saturation <93% on pulse oximetry for younger children.

 -  Ventilator dependent

 -  Known chromosomal abnormality

 -  Active cancer diagnosis. Neuroblastoma that requires only follow up is eligible.

 -  Pregnancy