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 Institute35 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Leukemia Myelodysplastic Syndromes

Eligibility

Sex: ALLMin age: 5 YearsMax age: 120 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Abnormal stromal function

Secondary Outcomes

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