Dyskeratosis Congenita, Fanconi Anemia, Myelodysplastic Syndromes, Pearson Marrow-pancreas Syndrome, Shwachman-diamond Syndrome
Conditions
Keywords
refractory cytopenia with multilineage dysplasia, aplastic anemia, Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Pearson marrow-pancreas syndrome
Brief summary
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.
Detailed description
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.
Interventions
GENETICpolymerase chain reaction
OTHERflow 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.
OTHERimmunologic technique
PROCEDUREbiopsy
Sponsors
University Hospital Freiburg
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of refractory cytopenia (RC) including any of the following: * Severe aplastic anemia (SAA) * Fanconi's anemia * Shwachman Diamond syndrome * Dyskeratosis congenita * Pearson syndrome * All RC patients included in the EWOG MDS 2006 protocol irrespective of therapy * Patients who have undergone hematopoietic stem cell transplantation (HSCT) may be enrolled on EWOG-MDS SCT RC RIC 06 or EWOG-MDS SCT MDS 06 protocol PATIENT CHARACTERISTICS: * Not specified PRIOR CONCURRENT THERAPY: * No prior immunosuppressive therapy for refractory cytopenia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunophenotype of patients with oligoclonal T-cell expansion | 96 months |
| Number of patients with glycophosphatidylinositol (GPI) deficient clones | 96 months |
| Number of patients with TCR V beta oligoclonality at diagnosis | 96 months |
Secondary
| Measure | Time frame |
|---|---|
| Failure-free survival | 96 months |
| Overall survival | 96 months |
| Number of patients with molecular response as compared to hematological response after IST | 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 | 96 months |
Countries
Austria, Belgium, Czechia, Denmark, Germany, Ireland, Italy, Netherlands, Spain, Switzerland
Outcome results
None listed