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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 Down Syndrome Myeloproliferative Disorders Leukemoid Reaction

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 and Research Center Oakland
    Oakland, California, 94609, United States
  • UCSF Helen Diller Family Comprehensive Cancer Center
    San Francisco, California, 94115, United States
  • 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
Lead Scientist
Study Type
Observational
Last Updated
July 24, 2017