Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors

OBJECTIVES:

• Determine whether autologous transplantation of mobilized CD34+ peripheral blood stem cells (PBSC) can provide complete hematologic reconstitution after myeloablative chemotherapy comprising etoposide (VP-16) and carboplatin (CBDCA) in patients with metastatic or recurrent rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma/primitive neuroectodermal tumor, germ cell tumors, childhood brain tumors, or hepatoblastoma.
• Determine the frequency and yield of CD34+ PBSC and granulocyte-macrophage colony-forming units (GM-CFU) that are mobilized, harvested, and purified after a single priming course of high-dose cyclophosphamide (CTX) followed by filgrastim (G-CSF).
• Correlate the number of CD34+ cells and GM-CFU in the autologous PBSC graft with time to engraftment of white blood cells, neutrophils, and platelets in these patients.
• Determine the optimal day of PBSC harvest after a single priming course of high-dose CTX and G-CSF in these patients.
• Determine whether CD34+ PBSC rescue and daily post-transplantation G-CSF decrease the time to hematopoietic recovery after high-dose VP-16 and CBDCA compared to historical results achieved in similar patients rescued with bone marrow.
• Compare the tumor cell content of marrow, mobilized blood, and purified CD34+ PBSC graft preparations.
• Determine the optimal timing of PBSC mobilization and harvest in relation to extent of prior chemotherapy in these patients.
• Determine the feasibility of a single leukapheresis for PBSC harvest in children.
• Determine the toxic effects of this regimen in these patients.
• Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of cyclophosphamide.

Mobilization/harvest: Patients receive cyclophosphamide IV over 90 minutes on day 0 and filgrastim (G-CSF) subcutaneously or IV over 30 minutes on days 2-15 or until blood counts recover. Peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on day 15. Bone marrow is also harvested in case insufficient PBSC are harvested.

Preparative regimen/transplantation: Patients receive carboplatin IV over 1 hour and etoposide IV continuously on days -6 to -4. Cyclophosphamide is administered IV over 1 hour on days -3 and -2 or IV continuously on days -3 and -2, -4 to -2, -5 to -2, or -6 to -2. PBSC or bone marrow is reinfused on day 0.

Cohorts of 3-10 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which 20% of patients experience dose-limiting toxicity.

At least 6 additional patients receive cyclophosphamide at the MTD.

PROJECTED ACCRUAL: A minimum of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven malignant solid tumor, including any of the following:

• Rhabdomyosarcoma
• Neuroblastoma
• Ewing's sarcoma/primitive neuroectodermal tumor
• Germ cell tumors
• Childhood brain tumors
• Hepatoblastoma
• Metastatic disease OR has failed at least first-line therapy
• Ineligible for higher priority protocols

PATIENT CHARACTERISTICS:

Age:

• Under 36 at transplantation

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm3
• Platelet count at least 75,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Liver function tests no greater than 2 times normal OR
• No active hepatitis on liver biopsy
• No hepatitis B infection

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Glomerular filtration rate (preferably measured) greater than 60% of normal

Cardiovascular:

• Left ventricular ejection fraction at least 45%
• No active congestive heart failure
• No active arrhythmia

Pulmonary:

• Age 8 and under: clinically normal pulmonary function
• Over age 8: FEV1 and FVC at least 50% predicted
• Arterial blood gases normal and DLCO at least 50% if spirograms difficult to
• interpret due to poor patient effort, recent surgery, or pulmonary tumor
• involvement

Other:

• No mucositis or mucosal infection prior to myeloablative chemotherapy
• HIV negative
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics