Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

Study Overview
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Brief Summary
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RATIONALE: Determination of genetic markers for soft tissue sarcoma or rhabdomyosarcoma may help doctors identify patients who are at risk for therapy-related leukemia. PURPOSE: Clinical trial to study genetic testing of children with soft tissue sarcoma or rhabdomyosarcoma to identify children who are at risk of developing leukemia from the chemotherapy used to treat sarcoma.

Detailed Description
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OBJECTIVES: Identify genetically susceptible patients to therapy-induced myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) prior to initiation of high-dose chemotherapy for sarcoma. Identify patients who are at increased risk of t-MDS/AML during or after therapy. OUTLINE: Blood is collected from patients at diagnosis (preferably before chemotherapy or transfusion), at end of therapy, and at 6 months, 1 year, 2 years, and 3 years after therapy. Blood specimens are examined by clonality analysis (HUMARA), variant cell frequency (glycophorin A assay), GST NAT2/CYP1A1 genotyping, microsatellite instability, and ras mutation detection (single strand conformation polymorphism and sequencing of mutant alleles). Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment. PROJECTED ACCRUAL: A total of 321 patients will be accrued for this study within 4 years.

Official Title
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Clinical and Biological Predictors of Therapy-Related Leukemia

Conditions
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Leukemia, Myelodysplastic Syndromes, Sarcoma

Intervention / Treatment
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* Genetic: clonality analysis
* Genetic: microsatellite instability analysis
* Genetic: mutation analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of sarcoma including: Rhabdomyosarcoma Ewing's sarcoma Primitive neuroectodermal tumor Fibrosarcoma Malignant peripheral nerve sheath tumor Synovial cell sarcoma Osteosarcoma Other soft tissue sarcoma Must be currently receiving intensive or high-dose chemotherapy for sarcoma PATIENT CHARACTERISTICS: Age: Children Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Identification of Genetical suceptibility prior to therapy<br>Determine the glutathione-s-transferase theta (GSTT1) or glutathione-s-transferase mu (GSTM1) null genotype is more frequent in individuals with t-MDS/AML. Determine the GSTT1 or GSTM1 null genotype is associated with a reduced incidence of relapse of sarcoma. Determine NAT2 or CYP1A1 genotype influences risk of t-MDS/AML. Determine development of a mutator phenotype as demonstrated by developing microsatellite instability is an early marker of individuals likely to progress to t-MDS/AML. | Genetic: microsatellite instability analysis<br> <br> Genetic: mutation analysis<br> <br> |
| Increased Risk Of T-MDS/AML before/after Therapy<br>Determine clonal hematopoiesis develops in children receiving high intensity alkylating agent chemotherapy for sarcomas. Determine development of clonal hematopoiesis is associated with increased frequency of t-MDS/AML. Determine measurement of somatic cell mutation frequency, measured by the glycophorin A (GPA) assay prior to and after chemotherapy will predict individuals at increased risk of t-MDS/AML. Identify individuals with ras gene mutations in normal peripheral blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML blood cells after therapy, and whether the identification of such mutations is associated with increased risk of t-MDS/AML. | Genetic: clonality analysis<br> <br> Genetic: microsatellite instability analysis<br> <br> Genetic: mutation analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secondary acute myeloid leukemia, secondary myelodysplastic syndromes, localized osteosarcoma, metastatic osteosarcoma, childhood soft tissue sarcoma, nonmetastatic childhood soft tissue sarcoma, metastatic childhood soft tissue sarcoma, childhood fibrosarcoma, childhood synovial sarcoma, childhood neurofibrosarcoma, previously untreated childhood rhabdomyosarcoma, localized Ewing sarcoma/peripheral primitive neuroectodermal tumor, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor