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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
Information provided by (Responsible Party):
Charlotte Niemeyer, MD, University Hospital Freiburg

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.

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

Detailed Description:



  • 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.

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Study Type : Observational
Actual Enrollment : 119 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Intervention Details:
  • 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

Primary Outcome Measures :
  1. Number of patients with TCR V beta oligoclonality at diagnosis [ Time Frame: 96 months ]
  2. Immunophenotype of patients with oligoclonal T-cell expansion [ Time Frame: 96 months ]
  3. Number of patients with glycophosphatidylinositol (GPI) deficient clones [ Time Frame: 96 months ]

Secondary Outcome Measures :
  1. Number of patients with molecular response as compared to hematological response after IST [ Time Frame: 96 months ]
  2. 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 ]
  3. Overall survival [ Time Frame: 96 months ]
  4. Failure-free survival [ Time Frame: 96 months ]

Biospecimen Retention:   Samples With DNA
Bone Marrow Peripheral blood cells

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients with MDS


  • 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


  • Not specified


  • No prior immunosuppressive therapy for refractory cytopenia

Information from the National Library of Medicine

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

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St. Anna Children's Hospital
Vienna, Austria, A-1090
Ghent University
Ghent, Belgium, B-9000
Czech Republic
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
Sponsors and Collaborators
University Hospital Freiburg
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Study Chair: Marry M. Van Den Heuvel-Eibrink, MD, PhD Erasmus MC - Sophia Children's Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Charlotte Niemeyer, MD, MD Prof. Dr. med. Niemeyer, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT00499070    
Other Study ID Numbers: CDR0000553058
EWOG-MDS-RC-06 ( Other Identifier: University Hospital Freiburg )
First Posted: July 11, 2007    Key Record Dates
Last Update Posted: January 16, 2015
Last Verified: January 2015
Keywords provided by Charlotte Niemeyer, MD, University Hospital Freiburg:
refractory cytopenia with multilineage dysplasia
aplastic anemia
Fanconi anemia
dyskeratosis congenita
Shwachman-Diamond syndrome
Pearson marrow-pancreas syndrome
Additional relevant MeSH terms:
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Shwachman-Diamond Syndrome
Fanconi Syndrome
Myelodysplastic Syndromes
Fanconi Anemia
Dyskeratosis Congenita
Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Congenital Bone Marrow Failure Syndromes
Bone Marrow Failure Disorders
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases
Urologic Diseases
Skin Abnormalities
Congenital Abnormalities
Genetic Diseases, X-Linked
Skin Diseases, Genetic
Skin Diseases
Exocrine Pancreatic Insufficiency
Pancreatic Diseases
Digestive System Diseases