Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment

NCT00499070 | Completed

• 2 other identifiers: CDR0000553058EWOG-MDS-RC-06
• Study Type: observational
• Target: 119
• Locations: 10 countries
• Sites: 10

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.

Conditions

Dyskeratosis Congenita; Fanconi Anemia; Myelodysplastic Syndromes; Pearson Marrow-pancreas Syndrome; Shwachman-diamond Syndrome

Keywords

refractory cytopenia with multilineage dysplasia; aplastic anemia; Fanconi anemia; dyskeratosis congenita; Shwachman-Diamond syndrome; Pearson marrow-pancreas syndrome

Outcome Measures

Primary Outcomes (3)

• Number of patients with TCR V beta oligoclonality at diagnosis

  96 months

• Immunophenotype of patients with oligoclonal T-cell expansion

  96 months

• Number of patients with glycophosphatidylinositol (GPI) deficient clones

  96 months

Secondary Outcomes (4)

• 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

• Overall survival

  96 months

• Failure-free survival

  96 months

Interventions

polymerase chain reaction GENETIC

flow cytometry OTHER

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.

immunologic technique OTHER

biopsy PROCEDURE

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

All patients with MDS

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital Freiburg: lead

Study Sites (10)

St. Anna Children's Hospital

Vienna, A-1090, Austria

Location

Ghent University

Ghent, B-9000, Belgium

Location

University Hospital Motol

Prague, 150 06, Czechia

Location

Arhus Universitetshospital - Skejby

Aarhus, 8200, Denmark

Location

Universitaetskinderklinik - Universitaetsklinikum Freiburg

Freiburg im Breisgau, D-79106, Germany

Location

Our Lady´s Hospital for Sick Children

Dublin, 12, Ireland

Location

Fondazione I.R.C.C.S. Policlinico San Matteo

Pavia, 27100, Italy

Location

Erasmus MC - Sophia Children's Hospital

Rotterdam, 3015 GJ, Netherlands

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

University Children's Hospital

Zurich, CH-8032, Switzerland

Location

Related Publications (2)

• Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Dworzak M, Hasle H, Locatelli F, De Moerloose B, Schmugge M, Mejstrikova E, Novakova M, Zecca M, Zwaan CM, Te Marvelde JG, Langerak AW, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH. Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood. Haematologica. 2015 Mar;100(3):315-23. doi: 10.3324/haematol.2014.107706. Epub 2014 Nov 25.

  PMID: 25425683 DERIVED

• Aalbers AM, van den Heuvel-Eibrink MM, Baumann I, Beverloo HB, Driessen GJ, Dworzak M, Fischer A, Gohring G, Hasle H, Locatelli F, De Moerloose B, Noellke P, Schmugge M, Stary J, Yoshimi A, Zecca M, Zwaan CM, van Dongen JJ, Pieters R, Niemeyer CM, van der Velden VH, Langerak AW. T-cell receptor Vbeta skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS. Blood Cancer J. 2014 May 2;4(5):e209. doi: 10.1038/bcj.2014.28.

  PMID: 24786393 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Bone Marrow Peripheral blood cells

MeSH Terms

Conditions

Dyskeratosis Congenita; Fanconi Anemia; Myelodysplastic Syndromes; VLCAD deficiency; Shwachman-Diamond Syndrome; Anemia, Aplastic

Interventions

Polymerase Chain Reaction; Flow Cytometry; Immunologic Techniques; Biopsy

Condition Hierarchy (Ancestors)

Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Anemia, Hypoplastic, Congenital; Anemia; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Exocrine Pancreatic Insufficiency; Pancreatic Diseases; Digestive System Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipomatosis

Intervention Hierarchy (Ancestors)

Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Marry M. Van Den Heuvel-Eibrink, MD, PhD

  Erasmus MC-Sophia Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Prof. Dr. med. Niemeyer

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: January 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: January 16, 2015

Record last verified: 2015-01

Locations

AU (1); IE (1); ES (1); CH (1); NL (1); CZ (1); IT (1); BE (1); DE (1); DK (1)