Clinical trial NCT00899795: 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
Official title: Stromal Injury and Clonal Adaptation in Myelodysplasia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 35
Sex: ALL
Minimum age (years): 5
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inpatient, outpatient, and normal volunteers

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.

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.

Eligibility 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)

Primary outcomes:
measure: Abnormal stromal function
Secondary outcomes:
measure: Clonal progenitors resistant to selected extracellular apoptotic cells
measure: Comparison of stromal function between secondary vs primary acute myeloid leukemia or myelodysplastic syndromes
measure: Influence of cytotoxic agents on supportive function of the bone marrow stroma
measure: Reduction of cytotoxicity and genotoxicity in hematopoietic progenitor cells and stromal cells with use of cytoprotective agents
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Grover C. Bagby, MD
role: PRINCIPAL_INVESTIGATOR
References: