Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
Trial status: Open for Enrollment
Why is this study being done?
- 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.
Who is eligible to participate?
- 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
- Not specified
PRIOR CONCURRENT THERAPY:
- Not specified