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This phase I trial investigates the side effects and effectiveness of chemotherapy followed by a donor (allogeneic) stem cell transplant when given to patients with high grade brain cancer. Chemotherapy drugs, such as fludarabine, thiotepa, etoposide, melphalan, and rabbit anti-thymocyte globulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.

PRIMARY OBJECTIVE:

I. To assess tolerability of allogenic hematopoietic cell transplantation (HCT) among patients with chemo-responsive high-grade central nervous system (CNS) malignancies as defined by transplant-related mortality (TRM) at day 30 as well as rate of grade III organ toxicity or higher (Bearman Regimen-Related Toxicities Scale) attributable to conditioning occurring within 30 days.

SECONDARY OBJECTIVES:

I. Median time to platelet and neutrophil engraftment. II. Incidence of acute graft-versus-host disease (aGVHD) by day 100. III. Incidence of chronic GVHD at day 100 and one year. IV. Rate of grade II organ toxicity through day 100. V. Rate of graft failure (primary and secondary) through day 100. VI. Rate of infectious complications through day 100. VII. Progression free survival at day 180. VIII. Cumulative incidence of relapse, overall survival, and progression-free survival at 100 days and 1 year.

OUTLINE:

Patients receive thiotepa intravenously (IV) over 2-4 hours and etoposide IV over 60 minutes on days -8 to -6, melphalan IV over 20 minutes on days -5 and -4, and fludarabine phosphate IV over 1 hour on days -5 to -3. Patients receiving umbilical cord transplant only also receive lapine T-lymphocyte immune globulin IV over 4-12 hours on days -4 and -3. Patients then undergo HCT on day 0. Patients also receive tacrolimus IV or cyclosporine IV beginning on day -2 to and mycophenolate mofetil orally (PO) every 8 hours or IV from days 0-40 and tapered to day 90.

After completion of study treatment, patients are followed up at 100, 180, 270 and 360 days.

Inclusion Criteria:

• Pathological criteria for any high grade primary or recurrent malignant brain tumor - medulloblastoma (patients who are ineligible for tandem autologous transplants or who are at least 3 months post autologous HCT), primitive neuroectodermal tumor (PNET), atypical teratoid rhabdoid tumor (ATRT), malignant glioma, CNS germ cell tumor, intracranial sarcomas, choroid plexus carcinoma, anaplastic ependymoma. High grade tumors defined as those that are grade III or higher based on World Health Organization (WHO) classification grading system or for medulloblastoma: group 3 and 4 molecular subtypes

• Patients have to be in at least, a chemo-responsive disease status

• Available suitable HCT donor

• Creatinine clearance or glomerular filtration rate (GFR) >= 50 ml/min/1.73m^2, and not requiring dialysis

• Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) >= 50% predicted. If unable to perform pulmonary function tests, then O2 saturation >= 92% in room air

• Bilirubin =< 3x upper limit of normal (ULN) (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5x for age

• DONOR: HCT will be done using stem cell sources in the following order of preference (and fulfilling minimal cell dose requirements per institutional standards):

  • Matched related donor bone marrow (10 of 10 human leukocyte antigen [HLA] alleles [HLA-A, B, C, DR, and DQ]). Matched related donor peripheral blood stem cell (PBSC) is allowed only if collection of bone marrow (BM) is not available or refused by guardian/donor

  • Matched allogeneic umbilical cord blood: related

    • High-resolution matching at A,B, DRB1 (minimum 4/6)
    • Killer-cell immunoglobulin-like receptor (KIR) major histocompatibility complex (MHC) class 1 preferential mismatch (minimum 4/6)

  • Matched allogeneic umbilical cord blood: unrelated

    • High-resolution matching at A,B, DRB1(minimum 4/6)
    • KIR MHC class 1 preferential mismatch (minimum 4/6)

Exclusion Criteria:

• Lack of histocompatible suitable graft source
• End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning regimen
• Renal failure requiring dialysis
• Congenital heart disease resulting in congestive heart failure
• Ventilatory failure: requires invasive mechanical ventilation
• Human immunodeficiency virus (HIV) infection
• Uncontrolled bacterial, viral, or fungal infections
• A female of reproductive potential who is pregnant, planning to become pregnant during the study, or is nursing a child
• Any patient who does not fulfill inclusion criteria listed above