Clinical trial NCT00499070: Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
Official title: TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
First posted: 2007-07-11
Enrollment: 119
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with MDS

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.

Eligibility 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

Primary outcomes:
measure: Number of patients with TCR V beta oligoclonality at diagnosis
timeFrame: 96 months
measure: Immunophenotype of patients with oligoclonal T-cell expansion
timeFrame: 96 months
measure: Number of patients with glycophosphatidylinositol (GPI) deficient clones
timeFrame: 96 months
Secondary outcomes:
measure: Number of patients with molecular response as compared to hematological response after IST
timeFrame: 96 months
measure: 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
timeFrame: 96 months
measure: Overall survival
timeFrame: 96 months
measure: Failure-free survival
timeFrame: 96 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: St. Anna Children's Hospital
city: Ghent
country: Belgium
facility: Ghent University
city: Prague
country: Czech Republic
facility: University Hospital Motol
city: Aarhus
country: Denmark
facility: Arhus Universitetshospital - Skejby
city: Freiburg
country: Germany
facility: Universitaetskinderklinik - Universitaetsklinikum Freiburg
city: Dublin
country: Ireland
facility: Our Lady´s Hospital for Sick Children
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Zurich
country: Switzerland
facility: University Children's Hospital
Study officials:
affiliation: Erasmus MC-Sophia Children's Hospital
name: Marry M. Van Den Heuvel-Eibrink, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.