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.
OBJECTIVES: Primary * 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. Secondary * 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
Enrollment
119
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.
St. Anna Children's Hospital
Vienna, Austria
Ghent University
Ghent, Belgium
University Hospital Motol
Prague, Czechia
Arhus Universitetshospital - Skejby
Aarhus, Denmark
Universitaetskinderklinik - Universitaetsklinikum Freiburg
Freiburg im Breisgau, Germany
Our Lady´s Hospital for Sick Children
Dublin, Ireland
Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia, Italy
Erasmus MC - Sophia Children's Hospital
Rotterdam, Netherlands
Hospital Sant Joan de Deu
Barcelona, Spain
University Children's Hospital
Zurich, Switzerland
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
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