• Maximum tolerated dose of tomotherapy [ Designated as safety issue: Yes ]
  

• Feasibility of performing PET scans and "spot radiation" to PET-positive lesions after transplantation [ Designated as safety issue: No ]
  
• Change in bone mineral density and turnover from baseline to 6 and 12 months after transplantation [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of tomographic total marrow irradiation (TMI) when given prior to an alkylator-intensive conditioning regimen in patients with high-risk or relapsed solid tumors.

Secondary

• To determine the feasibility of performing PET scans and spot radiation to PET-positive lesions after transplantation.
• To determine the change in bone mineral density and turnover in patients treated with an alkylator-intensive conditioning regimen and TMI.

OUTLINE:

• Mobilization chemotherapy and peripheral blood progenitor cell (PBPC) collection: Patients receive ifosfamide IV and etoposide IV on days -10 and -30. Beginning 24 hours after completion of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously (SC) or IV until blood counts recover. Patients then receive an increased dose of G-CSF SC or IV once daily for 3 consecutive days. Beginning on day -97, patients undergo up to 4 collections of PBPCs. Patients who do not yield an adequate number of cells undergo bone marrow harvest.
• Bone marrow harvest: Patients undergo bone marrow aspirate and biopsy 2 weeks after the last dose of G-CSF.

If the aspirate or biopsy is morphologically free of tumor cells and demonstrates > 20% cellularity, then patients receive sargramostim (GM-CSF) daily for 5 days followed by bone marrow harvest.

• Total marrow irradiation (TMI) with tomotherapy: Patients undergo escalating doses of TMI* to all bony sites using helical tomotherapy image-guided intensity-modulated radiotherapy on days -11 to -9.

NOTE: *Patients with primary CNS tumors do not receive TMI but are eligible to receive chemotherapy and hematopoietic progenitor cell rescue in accordance with the protocol.

• Conditioning regimen: Patients receive busulfan IV over 2 hours four times daily on days -8 to -6, high-dose melphalan IV over 30 minutes on days -5 to -4, and thiotepa IV over 2 hours on days -3 to -2.
• Autologous CD34+ hematopoietic progenitor cell transplantation: Patients undergo reinfusion of autologous G-CSF-mobilized peripheral blood or bone marrow progenitor cells on day 0. Patients also receive G-CSF support beginning on day 0 and continuing until blood counts recover for 2 consecutive days.
• Post-transplantation radiotherapy: Patients may receive additional radiotherapy to areas of known metastatic disease, PET-positive lesions, primary disease (if not previously irradiated to maximum tolerated dose), and lungs beginning on day 60 post transplantation. Patients with prior lung metastasis may receive up to 10 fractions of whole-lung irradiation. Patients may also receive additional radiotherapy to primary disease if maximum tolerated dose has not yet been reached.

Patients undergo bone mineral density studies at baseline and at days 60, 120, and 180 post transplantation.

Patients also undergo blood sample collection periodically during study for pharmacokinetic analysis of busulfan.

Patients undergo PET scans at baseline and on day 60.

After completion of study therapy, patients are followed at days 180 and 365 and then periodically thereafter.