Evaluating Cell Damage in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, or Fanconi Anemia; in Patients Who Were Exposed to Alkylating Agents; and in Healthy Volunteers

Study Overview
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Brief Summary
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RATIONALE: Studying samples of bone marrow from patients with cancer and from healthy volunteers in the laboratory may help doctors learn more about changes that occur in bone marrow stromal (connective tissue) cells. It may also help doctors understand the effects of alkylating agents on bone marrow stromal cells. PURPOSE: This laboratory study is evaluating stromal cells in patients with acute myeloid leukemia, myelodysplastic syndromes, or Fanconi anemia; in patients who were exposed to alkylating agents; and in healthy volunteers.

Detailed Description
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OBJECTIVES: Primary Determine abnormal stromal function in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or Fanconi anemia; in patients who were exposed to alkylating agents; and in healthy volunteers. Secondary Determine whether clonal progenitors from patients with secondary AML or MDS are resistant to selected extracellular apoptotic cues. Determine whether stromal function in patients with secondary AML or MDS is more aberrant than stromal function in patients with primary AML or MDS. Determine whether cytotoxic agents known to induce secondary MDS or AML influence the supportive function of the bone marrow stroma. Determine whether cytoprotective agents reduce both cytotoxicity and genotoxicity in hematopoietic progenitor cells and stromal cells. OUTLINE: Patients and healthy volunteers undergo bone marrow sample collection. Progenitor cells are grown in culture. Cell survival is quantified by flow cytometric and cytogenetic analysis, sister chromatid exchange, and FISH for chromosome 11 changes (for etoposide-exposed samples only). PROJECTED ACCRUAL: A total of 24 patients and healthy volunteers will be accrued for this study.

Official Title
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Stromal Injury and Clonal Adaptation in Myelodysplasia

Conditions
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Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Genetic: cytogenetic analysis
* Genetic: fluorescence in situ hybridization
* Other: flow cytometry
* Procedure: biopsy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Meets 1 of the following criteria: Diagnosis of acute myeloid leukemia or myelodysplastic syndromes and requires bone marrow aspiration/biopsy for clinical purposes Primary or secondary disease Diagnosis of Fanconi anemia by positive mitomycin C test (age 5 to 55 years) Received prior chemotherapy containing any of the following alkylating agents: mechlorethamine, chlorambucil, cyclophosphamide, melphalan, busulfan, or topoisomerase inhibitors Healthy volunteer (age 18 and over), meeting the following criteria: CBC normal WBC > 1,000/mm³ Hemoglobin > 10 g/dL Platelet count > 70,000/mm³ No bone marrow metastases No evidence of non-hematopoietic malignancy PATIENT CHARACTERISTICS: ECOG performance status 0-2 No clinical signs and symptoms of acute or subacute infection (viral, bacterial, or fungal infection) No allergy to lidocaine or xylocaine PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 6 months since prior cytotoxic or immunosuppressive agents No prior extensive pelvic radiotherapy (> 20 Gy)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: cytogenetic analysis|nan|
|Genetic: fluorescence in situ hybridization|nan|
|Other: flow cytometry|nan|
|Procedure: biopsy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abnormal stromal function |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clonal progenitors resistant to selected extracellular apoptotic cells |  |  | 
| Comparison of stromal function between secondary vs primary acute myeloid leukemia or myelodysplastic syndromes |  |  | 
| Influence of cytotoxic agents on supportive function of the bone marrow stroma |  |  | 
| Reduction of cytotoxicity and genotoxicity in hematopoietic progenitor cells and stromal cells with use of cytoprotective agents |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, untreated adult acute myeloid leukemia, childhood myelodysplastic syndromes