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

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00899795

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

100

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Other: flow cytometry Procedure: biopsy

Detailed 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.

Study Design

Study Type:

Observational

Actual Enrollment :

35 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Stromal Injury and Clonal Adaptation in Myelodysplasia

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Outcome Measures

Primary Outcome Measures

Abnormal stromal function []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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