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

TCR Vbeta Repertoire and PNH Clones in Children With Refractory Cytopenia (RC). An Open Nonrandomised Multi-Center Prospective Study

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.

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