Brief Summary
This research study is looking at blood samples from newborns with Down syndrome. Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.
Brief Title
Study of Blood Samples From Newborns With Down Syndrome
Detailed Description
PRIMARY OBJECTIVES:
I. 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.
II. 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.
III. 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.
IV. 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.
V. To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
VI. To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
VII. 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.
VIII. 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.
I. 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.
II. 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.
III. 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.
IV. 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.
V. To evaluate the relationship between karyotype (including FISH analysis) and subsequent leukemia in TMD patients.
VI. To examine pharmacogenetics and in vitro drug sensitivity to cytarabine (MTT assay) in blasts from TMD patients.
VII. 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.
VIII. 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Myeloid Proliferations Associated With Down Syndrome
Eligibility Criteria
Inclusion Criteria:
* 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
* 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
Inclusion Criteria
Inclusion Criteria:
* 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
90 Days
NCT Id
NCT00959283
Org Class
Network
Org Full Name
Children's Oncology Group
Org Study Id
AAML08B1
Overall Status
Completed
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Biology Study of Transient Myeloproliferative Disorder (TMD) in Children With Down Syndrome (DS)
Primary Outcomes
Outcome Measure
Event-free survival
Outcome Time Frame
Up to 5 years
Secondary Ids
Secondary Id
NCI-2011-02193
Secondary Id
COG-AAML08B1
Secondary Id
CDR0000636115
Secondary Id
AAML08B1
Secondary Id
AAML08B1
Secondary Id
AAML08B1
Secondary Id
U10CA098543
Secondary Id
UG1CA189958
Secondary Outcomes
Outcome Time Frame
Up to 5 years
Outcome Measure
Overall survival
Outcome Time Frame
Up to 5 years
Outcome Measure
Incidence of TMD-related mortality
Outcome Time Frame
Up to 5 years
Outcome Measure
Incidence of subsequent leukemia for patients with resolved TMD
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Study Population
Newborns with transient myeloproliferative disorder (TMD)
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
0
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Lisa Gennarini
Investigator Email
lfigueir@montefiore.org
Investigator Phone