Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia

• Comparison of the Level of IS as Assessed by Immuknow Assay in Responders and Non-responders [ Time Frame: Every 2 weeks for 3 months beginning on day 1 of therapy and then monthly (for a total of 6 months) ] [ Designated as safety issue: No ]
• Reduction of VB Repertoire Associated With r-ATG/CsA Combination [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
  We will perform molecular analysis of the TCR repertoire to identify "marker" immunodominant clone specimens using VB typing.

RATIONALE: Immunosuppressive therapies, such as anti-thymocyte globulin and cyclosporine, may improve bone marrow function and increase blood cell counts. PURPOSE: This phase II trial is studying how well giving anti-thymocyte globulin together with cyclosporine as first-line therapy works in treating patients with severe aplastic anemia.

PRIMARY OBJECTIVES: To determine the response rate of r-ATG and CsA in the first line setting. SECONDARY OBJECTIVES: To determine the level of IS as assessed by Immuknow assay in responders and compare it to non-responders. OUTLINE:Patients receive anti-thymocyte globulin IV over 4-24 hours daily on days 1-5. Beginning on day 6, patients receive oral cyclosporine twice daily for 6 months followed by a taper. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Drug: cyclosporine
  Given orally
  Other Names:

  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
• Other: flow cytometry
  Correlative studies
• Biological: anti-thymocyte globulin
  Given IV
  Other Names:

  • ATG
  • ATGAM
  • lymphocyte immune globulin
  • Thymoglobulin

Inclusion Criteria:

• All patients with sAA as defined by Camitta who are candidates for IS therapy; these criteria include bone marrow cellularity < 25% or 25-50% with < 30% of hematopoietic cells; it should also have two of the following three parameters: peripheral blood neutrophils < 0.5 x 10^9/L, platelets < 20 x 10^9/L and reticulocytes < 60 x 10^9/L in anemic patients
• If cytogenetic testing has been done, it should show normal karyotype or be not informative
• Patients should be either unwilling or otherwise ineligible (age, comorbidities, lack of donor) for bone marrow transplantation as a therapeutic modality
• Not previously treated with ATG for sAA
• Patients must have ECOG performance status of 0, 1, or 2
• Vitamin B12 and folic acid deficiency must be ruled out by measurement of serum levels
• Patients must have had a bone marrow biopsy examination in the three months prior to enrolling in the study
• Must be able to provide informed consent
• Systemic and other hematologic causes of pancytopenia, based on clinical presentation, must have been ruled out

Exclusion Criteria:

• Patients with clinically evident congestive heart failure, serious cardiac arrhythmias; symptoms of coronary artery disease must be cleared by cardiology prior to therapy
• Patients who have had chemotherapy, radiotherapy, or immunotherapy or other investigational drug use within 3 weeks prior to study entry
• Pregnant women
• All females of childbearing potential must have a blood test or urine study within two weeks prior to induction registration to rule out pregnancy
• Women of childbearing potential are strongly advised to use an accepted and effective method of contraception
• Patients who have medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results