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Summary

for people ages up to 1 year (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

RATIONALE: Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.

PURPOSE: This research study is looking at blood samples from newborns with Down syndrome.

Official Title

Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)

Details

OBJECTIVES:

  • To further our biological understanding of the natural history of transient myeloproliferative disorder (TMD) and its relationship to subsequent leukemia by facilitating the development of a TMD cell and protein bank, and repository of DNA/RNA from megakaryoblasts for future biological studies.
  • To investigate the biology of TMD molecular changes associated with resolution of TMD or its conversion to acute myeloid leukemia within each mortality-risk group by conducting GATA1 mutational analyses, hematopoiesis clonality studies, assessment of RAS mutations, and genomic instability studies using glycophorin A assays.
  • To determine if high-resolution microarray genomic analysis of TMD blasts (using Affymetrix SNP Genechip technology to assess gene expression, copy number variation, and loss of heterozygosity) can predict the development of subsequent leukemia.
  • To determine the relationship of minimal residual disease (monitored by peripheral blood flow cytometry and GATA1 mutational studies) to clinical remission status and development of subsequent leukemia within each mortality-risk group of TMD patients.
  • To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
  • To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
  • To examine the relationship of functional polymorphisms in Phase I and Phase II drug detoxification genes, DNA repair, and DNA synthesis pathways that may modify susceptibility to leukemia and outcome in TMD patients.
  • To determine the relationship between fibrosis-associated serum factors (e.g., platelet-derived growth factor, transforming growth factor beta, N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid) and event-free survival.

OUTLINE: This is a multicenter study.

Patients undergo peripheral blood collection periodically for biomarker analysis. Samples are analyzed for GATA1 mutations by real-time PCR, polymorphisms, cytogenetics, - and K-RAS mutations, gene expression, drug sensitivity patterns, and minimal residual disease by flow cytometry.

Patients are followed up periodically for 5 years.

Keywords

Leukemia acute myeloid leukemia/transient myeloproliferative disorder

Eligibility

For people ages up to 1 year

DISEASE CHARACTERISTICS:

  • Diagnosis of transient myeloproliferative disorder (TMD) at < 90 days of age and meeting 1 of the following criteria:
  • A diagnosis of Down syndrome or Down syndrome mosaicism AND non-erythroid and non-lymphoid blasts (any amount) in the peripheral blood verified with a second sample
  • Patients with typical physical characteristics of Down syndrome are allowed before cytogenetic or FISH confirmation of the diagnosis
  • Trisomy 21-positive leukemic blasts documented by biopsy of any organ (including

    5% non-erythroid/non-lymphoid blasts documented by bone marrow aspirate or biopsy)

  • Infants with isolated trisomy 21 positivity identified only in the leukemic blasts are allowed
  • Institutional immunophenotype characterization is required for study enrollment

PATIENT CHARACTERISTICS:

  • Not specified

PRIOR CONCURRENT THERAPY:

  • Not specified

Locations

  • Children's Hospital Central California
    Madera, California, 93638-8762, United States
  • Lucile Packard Children's Hospital at Stanford University Medical Center
    Palo Alto, California, 95798, United States
  • University of California Davis Cancer Center
    Sacramento, California, 95817, United States
  • Sutter Cancer Center
    Sacramento, California, 95816, United States
  • Childrens Hospital Los Angeles
    Los Angeles, California, 90027, United States
  • Southern California Permanente Medical Group
    Los Angeles, California, 90027, United States
  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    Los Angeles, California, 90048-1865, United States
  • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
    Long Beach, California, 90801, United States
  • Children's Hospital of Orange County
    Orange, California, 92868, United States
  • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    Loma Linda, California, 92354, United States
  • CCOP - Nevada Cancer Research Foundation
    Las Vegas, Nevada, 89109-2306, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Children's Oncology Group
ID
NCT00959283
Study Type
Observational
Last Updated
July 1, 2017