• Feasibility [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Graft-versus-tumor effects [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the percentage of patients with high-risk, recurrent pediatric sarcoma who achieve full donor engraftment by day 100 after treatment with induction chemotherapy followed by allogeneic/syngeneic peripheral blood stem cell transplantation.
• Determine the toxic effects of this regimen in these patients.
• Determine the incidence of graft-vs-host disease (GVHD) and the immune reconstitution rate in patients treated with this regimen.
• Determine whether allogeneic graft-vs-tumor responses after this regimen can induce clinically significant anti-tumor effects in these patients.
• Correlate evidence of increased thymic metabolic activity on fludeoxyglucose F 18 (FDG) positron-emission tomography (PET) scanning with immune reconstitution parameters in patients treated with this regimen.
• Evaluate FDG-PET scanning as a measure of disease activity in these patients by correlation with standard radiologic modalities and clinical outcome.

Secondary

• Evaluate the use of sirolimus and abbreviated tacrolimus as GVHD prophylaxis in these patients.

OUTLINE:

• Induction Chemotherapy: Patients receive induction chemotherapy comprising fludarabine IV over 30 minutes on days 1-3; etoposide IV continuously, doxorubicin IV continuously, and vincristine IV continuously on days 1-4; cyclophosphamide IV over 30 minutes on day 5; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days (until CD4 count is less than 50/mm^3) for up to 3 courses in the absence of disease progression or unacceptable toxicity.
• Preparative Regimen: Beginning 22 days after the last course of induction chemotherapy, patients begin the transplantation preparative regimen. Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3 and melphalan IV over 15 minutes on day -2. Allogeneic peripheral blood stem cells are infused on day 0. Patients then receive G-CSF SC beginning on day 0 and continuing until blood counts recover.
• Graft-vs-host disease (GVHD) prophylaxis (first 17 patients [closed to accrual as of 4/9/05]): Patients receive GVHD prophylaxis comprising cyclosporine IV over 2 hours every 12 hours beginning on day -1. Once oral feedings are tolerated, patients receive oral cyclosporine every 12 hours until day 28 (possibly longer if GVHD develops) followed by a taper over 2-4 weeks.* NOTE: *Patients with a genotypically identical twin stem cell donor do not receive GVHD prophylaxis
• GVHD prophylaxis (additional patients): Patients receive GVHD prophylaxis comprising tacrolimus IV or orally beginning on day -1 and continuing for at least 28 days and oral sirolimus beginning on day 3 and continuing for approximately 100 days.
• Lymphocyte Infusion: Approximately 28 days post-transplantation, patients receive 3 donor lymphocyte infusions every 2-4 weeks provided there has been no evidence of GVHD. Patients with persistent or progressive disease may receive adjuvant chemotherapy with standard disease-specific agents or be taken off study.

Patients are followed 1-2 times weekly for the first 100 days post-transplantation, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.