Vinblastine/Prednisone Versus Single Therapy With Cytarabine for Langerhans Cell Histiocytosis (LCH)

Inclusion Criteria: 1. Patient must have biopsy-confirmed diagnosis of Langerhans cell histiocytosis. 2. Patient must be between 0-21 years of age. 3. Patient must have a Karnofsky performance score ≥ 50% or Lansky performance score ≥ 50%. Exclusion Criteria: 1. Patient may not have received any prior systemic cytotoxic or other chemotherapies for LCH or any other malignant disorder prior to the initiation of protocol therapy on TXCH LCH0115 with the exception of: Steroid pretreatment: Systemic glucocorticosteroids (prednisone, methylprednisone, dexamethasone, etc.) for less than or equal to 120 hours (5 days) in the 7 days prior to initiating protocol therapy or for less than or equal to 336 hours (14 days) in the 28 days before the initiation of protocol therapy does not affect eligibility. The dose of steroid previously given does not affect eligibility. Patients who have only received surgical or radiation therapy, intralesional injection of steroids, inhalational steroids, systemic mineralocorticoids (hydrocortisone), or topical steroids may also be enrolled. 2. Patient may not have disease limited to a single skin or bone site, with the following exceptions: * Central Nervous System (CNS) risk lesions/special site disease: patients with single bone sites that are CNS-risk (sphenoid, mastoid, orbital, zygomatic, ethmoid, maxillary, or temporal bones, the cranial fossa, pituitary gland or neurodegenerative disease) or are "special sites" (odontoid peg, vertebral lesion with intraspinal soft tissue extension) require systemic therapy as standard of care and thus are eligible for the study. * Functionally critical lesions: A single lesion not described above which may cause "functionally critical anatomic abnormality" wherein attempts at local therapy (such as surgical curettage or radiation) would cause unacceptable morbidity. These patients may be enrolled with written approval of the Coordinating Center PI or Vice-Chair and documentation of the rationale justifying systemic therapy. * Asynchronous multisite LCH presentation: A patient may also have any single site of disease involvement at the time of enrollment if they previously had at least one other site of LCH disease in the past (which may have been treated with local therapy/surgery as described), as long as no systemic therapy was previously given per protocol guidelines. 3. Patient may not have severe renal disease (creatinine greater than 3 times normal for age OR creatinine clearance \< 50 ml/m2/1.73m\^2). 4. Patient may not have severe hepatic disease (direct bilirubin greater than 3 mg/dl OR aspartate aminotransferase (AST) greater than 500 IU/L), unless hepatic injury is due to LCH. 5. Female patients may not be pregnant or breastfeeding. 6. Patients of reproductive potential not willing to use an adequate method of birth control for the duration of the study. 7. Patients who are HIV positive may not be enrolled. NOTE: Patients excluded for laboratory abnormalities or performance score only may be enrolled on the study with written approval from the Coordinating Center PI or Vice-Chair.