Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy 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.

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