OBJECTIVES:

• Determine the dose-limiting toxicity of amifostine chemoprotection with peripheral blood stem cell transplantation plus chemotherapy in patients with high-risk or relapsed solid tumors or brain tumors.
• Determine response or time to disease progression in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of amifostine. Patients are stratified according to age (1 to 18 vs 19 to 45 years).

All patients receive filgrastim (G-CSF) IV for 1 week. On day 6 of G-CSF administration, patients undergo peripheral blood stem cell (PBSC) harvest followed by chemotherapy.

Patients receive oral busulfan every 6 hours on days -8 to -6 followed by melphalan IV over 30 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2. Patients receive amifostine IV over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. PBSC are reinfused on day 0.

Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed on day 50; at 3, 6, and 9 months; and at 1, 2, and 3 years post PBSC transplantation.

PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed high-risk or relapsed solid tumors or brain tumors, including:

  • Metastatic or relapsed Ewing's sarcoma
  • Metastatic or relapsed rhabdomyosarcoma
  • Refractory Wilms' tumor
  • Diffuse anaplastic Wilms' tumor
  • Stage III or IV neuroblastoma
  • Recurrent retinoblastoma
  • Metastatic or relapsed germ cell tumors
  • Metastatic or relapsed other soft tissue sarcomas
  • Small cell ovarian sarcoma
  • Metastatic or relapsed primitive neuroectodermal tumors of the bone
  • Recurrent brain tumors
  • Desmoplastic small round cell tumors
  • Recurrent or metastatic chordomas
  • Metastatic or relapsed hepatoblastoma
• No osteogenic sarcoma
• Patients receive peripheral blood stem cell transplantation only if in complete remission or in very good partial remission with no disease progression
• Must have radiologic, nuclear image, or histologic verification of relapse

PATIENT CHARACTERISTICS:

Age:

• 1 to 45

Performance status:

• Karnofsky 70-100%

Life expectancy:

• More than 4 months

Hematopoietic:

• No uncontrolled bleeding
• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin count at least 10 g/dL

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT or SGPT less than 2.5 times ULN

Renal:

• Creatinine less than 2 times ULN
• Creatinine clearance greater than 70 mL/min

Cardiovascular:

• Cardiac shortening fraction greater than 30%
• Cardiac ejection fraction greater than 45%
• No congestive heart failure
• No uncontrolled hypertension

Pulmonary:

• No asthma

Other:

• Not pregnant or nursing
• No uncontrolled metabolic disease
• No active severe infection
• No allergy to aminothiol compounds

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 week since prior hematopoietic growth factor and recovered
• No prior bone marrow transplantation

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Recovered from any prior therapy
• No other concurrent investigational agents