Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas

INCLUSION CRITERIA: PATIENT The following diagnoses will be considered: Patients with Ewing's sarcoma family of tumors, or alveolar rhabdomyosarcoma in one of the following categories: Patients who present at the time of initial diagnosis with bone or bone marrow metastases may be enrolled after completion of standard front-line therapy. Standard front line therapy for alveolar rhabdomyosarcoma should include vincristine and cyclophosphamide, plus actinomycin D and/or adriamycin. For patients with Ewing's sarcoma, standard front line therapy should include vincristine, cyclophosphamide, adriamycin, ifosfamide and etoposide. Patients with recurrence of tumor at any site less than one year after completing standard front-line therapy or with a second or subsequent recurrence at any time after completing standard front-line therapy. Patients with progression or persistence of disease while receiving standard front-line chemotherapy who cannot achieve a complete response (CR) with local treatment modalities. The following patients with desmoplastic small round cell tumor are eligible after receiving front line standard therapy, which is defined as a regimen containing at least vincristine, cyclophosphamide, and adriamycin: unresectable disease metastatic tumor (abdominal and extra-abdominal disease) progressive or persistent while receiving standard therapy recurrence within one year of completing therapy Patients without evaluable tumor at the time of enrollment are eligible Patients who have previously received high-dose chemotherapy with autologous stem cell rescue are eligible for this trial. Patient age 5-35 at enrollment. Availability of a 5 or 6 antigen human leukocyte antigen (HLA)-matched first-degree relative donor (single HLA-A or B mismatch allowed). Genotypically identical twins may serve as stem cell donors. Genotypic identity must be confirmed by restrictive fragment length polymorphism (RFLP) analysis. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or, for children less than or equal 10 years of age, Lansky greater than or equal 60 Cardiac function: Left ventricular ejection fraction greater than or equal to 45% by multi-gated acquisition scan (MUGA), fractional shortening greater than or equal 28% by echocardiogram (ECHO) or left ventricular ejection fraction greater than or equal 55% by ECHO. Pulmonary function: carbon monoxide diffusing capacity (DLCO) greater than or equal to 50% of the expected value corrected for alveolar volume. Renal function: Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than or equal to 60 ml/min/1.73 m^2. Age (years) Maximum serum creatinine (mg/dl) less than or equal to 5 0.8 greater than 5, less than or equal to 10 1.0 greater than 10, less than or equal to15 1.2, greater than 15 1.5 Liver function: Serum total bilirubin less than 2 mg/dl, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit of normal. Marrow function: absolute neutrophil count (ANC) must be greater than 750/mm^3 (unless due to underlying disease in which case there is no grade restriction), platelet count must be greater than or equal to 75,000/mm^3 (not achieved by transfusion) unless due to underlying disease in which case there is no grade restriction). Lymphopenia, cluster of differentiation 4 (CD4) lymphopenia, leukopenia, and anemia will not render patients ineligible. Ability to give informed consent. For patients less than18 years of age their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent. Durable power of attorney form completed (patients greater than or equal to18 years of age only). INCLUSION CRITERIA: DONOR Weight greater than or equal 15 kilograms. First degree relative with genotypic identity at 5 or 6 HLA loci (single HLAA or B locus mismatch allowed). Genotypically identical twins may serve as stem cell donors. Genotypic identity must be confirmed by RFLP analysis. For donors less than 18 years of age, he/she must be the oldest suitable donor, their legal guardian must give informed consent, the donor must give verbal assent, and he/she must be cleared by social work and a mental health specialist to participate. For donors greater than or equal to 18 years of age, ability to give informed consent. Adequate peripheral venous access for apheresis or consent to use a temporary central venous catheter for apheresis. Donor selection criteria will be in accordance with National Institutes of Health (NIH)/Clinical Center (CC) Department of Transfusion Medicine Standards. EXCLUSION CRITERIA: PATIENT Uncontrolled fungal infection. History of untreated CNS tumor involvement. Extradural masses which have not invaded the brain parenchyma (as is commonly observed in Ewing's sarcoma family of tumors) or parameningeal tumors (as is commonly observed in rhabdomyosarcoma) without evidence for leptomeningeal spread will not render the patient ineligible. Patients with previous central nervous system (CNS) tumor involvement that has been treated and has been stable for at least 6 weeks are eligible. Lactating or pregnant females. Human immunodeficiency virus (HIV) positive (due to unacceptable risk following allogeneic transplantation). Hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive with elevated liver transaminases. All patients with chronic active hepatitis (including those on treatment) are ineligible. High risk of inability to comply with transplant protocol, or inability to give appropriate informed consent in the estimation of the principal investigator (PI), social work, or the stem cell transplant team. Fanconi Anemia EXCLUSION CRITERIA: DONOR History of medical illness which poses a risk to donation in the estimation of the PI or the Department of Transfusion Medicine physician including, but not limited to stroke, hypertension that is not controlled with medication, or heart disease. Individuals with symptomatic angina or a history of coronary bypass grafting or angioplasty will not be eligible. History of congenital hematologic, immunologic, oncologic or metabolic disorder, which poses a prohibitive risk to the recipient in the estimation of the PI. Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000/micro l). Lactating or pregnant females. Donors of childbearing potential must use an effective method of contraception during the time they are receiving growth colony stimulating factor (G-CSF). The effects of cytokine administration on a fetus are unknown and may be potentially harmful. The effects upon breast milk are also unknown and may potentially be harmful to the infant. Human immunodeficiency virus (HIV)-positive, hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive. Donors are providing an allogeneic blood product and there is the potential risk of transmitting these viral illnesses to the recipient. High risk of inability to comply with transplant protocol.