Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
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|ClinicalTrials.gov Identifier: NCT00499070|
Recruitment Status : Completed
First Posted : July 11, 2007
Last Update Posted : January 16, 2015
RATIONALE: Studying biopsy, bone marrow, and blood samples from patients with cytopenia that did not respond to treatment may help doctors learn more about the disease and plan the best treatment.
PURPOSE: This laboratory study is assessing immune function in young patients with cytopenia that did not respond to treatment.
|Condition or disease||Intervention/treatment|
|Dyskeratosis Congenita Fanconi Anemia Myelodysplastic Syndromes Pearson Marrow-pancreas Syndrome Shwachman-diamond Syndrome||Genetic: polymerase chain reaction Other: flow cytometry Other: immunologic technique Procedure: biopsy|
- To evaluate the value of TCR V beta repertoire analysis for the determination of autoimmunity in refractory cytopenia (RC).
- To evaluate which immunophenotypic hematopoietic subclones are associated with oligoclonal T-cell expansion in RC.
- To evaluate the presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in RC.
- To compare the molecular response with the hematologic response in patients with RC after treatment with immunosuppressive therapy (IST).
- To compare the molecular response with human leukocyte histocompatability antigen (HLA) expression in patients with RC after treatment with IST.
OUTLINE: This is an open-label, multicenter, nonrandomized, prospective study.
Patients undergo biopsy, bone marrow, and blood sample collection periodically for immunological studies. Samples are analyzed for TCR V beta repertoire and paroxysmal nocturnal hemoglobinuria (PNH) clone analysis via PCR heteroduplex analysis and immunophenotyping of CD14, CD16 , CD55, CD59, and CD24 expression via flow cytometry.
|Study Type :||Observational|
|Actual Enrollment :||119 participants|
|Official Title:||TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study|
|Study Start Date :||January 2007|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||August 2012|
- Genetic: polymerase chain reaction
- Other: flow cytometry
For analyzing GPI deficient clones full blood will be analyzed by phenotyping using flowcytometry. For that purpose CD14, CD16 and CD24 expression will be evaluated in CD45 positive cells. Erythroid cells will be evaluated for CD55 and CD59 expression searching for clear populations with a lack of GPI-linked molecules. In addition, immunophenotyping using flowcytometry will be performed to evaluate which differentiation stages of the major hematopoietic lineages in BM and PB are associated with TCRVβ repertoire skewing. Comparison between BM and PB will identify which is the optimal compartment to analyze the responsible hematopoietic clones.
- Other: immunologic technique
- Procedure: biopsy
- Number of patients with TCR V beta oligoclonality at diagnosis [ Time Frame: 96 months ]
- Immunophenotype of patients with oligoclonal T-cell expansion [ Time Frame: 96 months ]
- Number of patients with glycophosphatidylinositol (GPI) deficient clones [ Time Frame: 96 months ]
- Number of patients with molecular response as compared to hematological response after IST [ Time Frame: 96 months ]
- Number of patients with HLA-DR15 antigen expression and molecular response as compared to number of patients with other HLA-DR antigens and molecular response [ Time Frame: 96 months ]
- Overall survival [ Time Frame: 96 months ]
- Failure-free survival [ Time Frame: 96 months ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00499070
|St. Anna Children's Hospital|
|Vienna, Austria, A-1090|
|Ghent, Belgium, B-9000|
|University Hospital Motol|
|Prague, Czech Republic, 150 06|
|Arhus Universitetshospital - Skejby|
|Aarhus, Denmark, 8200|
|Universitaetskinderklinik - Universitaetsklinikum Freiburg|
|Freiburg, Germany, D-79106|
|Our Lady´s Hospital for Sick Children|
|Dublin, Ireland, 12|
|Fondazione I.R.C.C.S. Policlinico San Matteo|
|Pavia, Italy, 27100|
|Erasmus MC - Sophia Children's Hospital|
|Rotterdam, Netherlands, 3015 GJ|
|Hospital Sant Joan de Deu|
|Barcelona, Spain, 08950|
|University Children's Hospital|
|Zurich, Switzerland, CH-8032|
|Study Chair:||Marry M. Van Den Heuvel-Eibrink, MD, PhD||Erasmus MC - Sophia Children's Hospital|