Busulfan, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk Ewing's Tumors

RATIONALE: Giving chemotherapy drugs, such as busulfan, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of tumor cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal tissues. Giving tacrolimus, sirolimus, and mycophenolate mofetil may stop this from happening.

PURPOSE: This phase II trial is studying how well giving busulfan together with melphalan and thiotepa followed by a donor stem cell transplant works in treating patients with high-risk Ewing's tumors.

OBJECTIVES:

* Evaluate disease-free and overall survival of patients with high-risk tumors of the Ewing's family treated with unmodified T-cell depleted allogeneic hematopoietic stem cell transplantation after cytoreduction comprising busulfan, melphalan, and thiotepa.
* Determine the regimen-related morbidity and mortality in these patients.
* Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
* Determine the biologic response of minimal residual disease in patients treated with this regimen.

OUTLINE: This is a prospective study.

* Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -8 to -6, melphalan IV over 20 minutes on days -5 to -3, and thiotepa IV over 4 hours on day -2.
* Allogeneic hematopoietic stem cell transplant: Patients undergo allogeneic bone marrow or T-cell depleted peripheral blood stem cell transplantation on day 0.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive treatment according to institutional guidelines and are given treatment against infection.

After completion of study treatment, patients are followed periodically for at least 3 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of high-risk tumors of the Ewing's family as defined by 1 of the following:

  * Biopsy-proven disease with distant metastases to sites other than the lung
  * Relapsed disease after completion of prior standard front-line therapy or high-dose chemotherapy
* Currently in complete remission (CR) with no evidence of disease (with or without minimal residual disease) or very good partial remission (i.e., CR with an abnormal bone scan) after prior standard or high-dose chemotherapy with local control
* HLA-compatible stem cell donor available

  * Compatible donors include those matched at both HLA-A, -B, -C, -DR and 1 of 2 -DQ alleles by high-resolution molecular typing
  * Related or unrelated donor

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 70-100% (≥ 16 years old) OR Lansky PS 70-100% (\< 16 years old)
* LVEF \> 50% at rest
* SGOT \< 3 times upper limit of normal
* Bilirubin \< 2.0 mg/dL (unless liver is involved with disease)
* Creatinine normal AND/OR creatinine clearance \> 60 mL/min
* Lung diffusion capacity \> 50% of predicted (corrected for hemoglobin) OR asymptomatic with a room air oxygen saturation of ≥ 98%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active uncontrolled viral, bacterial, or fungal infection
* No HIV-1 or -2 positivity

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior therapy with 100 mg/m² of melphalan
* No prior high-dose chemotherapy requiring autologous stem cell rescue
* No prior radiotherapy to \> 50% of the pelvic marrow space