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

OHSU Knight Cancer Institute

Status: Completed

Conditions: Leukemia; Myelodysplastic Syndromes

Treatments: Genetic: fluorescence in situ hybridization; Procedure: biopsy; Other: flow cytometry; Genetic: cytogenetic analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00899795

CDR0000445436 (Other Identifier)

P30CA069533 (U.S. NIH Grant/Contract)

OHSU-HEM-02008-LX

IRB00001025

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 35 patients

Sex: All

Ages: 5 to 120 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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)