S0020 Immunosuppressive Therapy in Treating Patients With Myelodysplastic Syndrome
S0020 Immunosuppressive Therapy in Treating Patients With Myelodysplastic Syndrome
RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be an
 effective treatment for myelodysplastic syndrome.

 PURPOSE: Phase II trial to study the effectiveness of antithymocyte globulin plus
 cyclosporine in treating patients who have myelodysplastic syndrome.
OBJECTIVES:

 -  Determine the response in patients with myelodysplastic syndromes treated with
 anti-thymocyte globulin and cyclosporine.

 -  Determine the frequency and severity of toxic effects of this regimen in these patients.

 -  Assess the correlation between response to treatment and the in vitro assessment of
 T-lymphocyte subsets in these patients.

 OUTLINE: This is a multicenter study. Patients are stratified according to myelodysplastic
 syndrome subclassification (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with
 excess blasts).

 Patients receive induction therapy comprising anti-thymocyte globulin IV over 6-12 hours on
 days 1-4 and oral cyclosporine twice daily on days 5-94 followed by a taper until day 124.
 Patients who relapse after a response of at least 60 days may receive reinduction therapy
 comprising oral cyclosporine twice daily on days 1-90 followed by a taper until day 120.
 Treatment continues in the absence of disease progression or unacceptable toxicity.

 Patients are followed monthly for 6 months, every 2 months for 2 years, and then every 6
 months for 3 years.

 PROJECTED ACCRUAL: A total of 130 patients (53 with refractory anemia [RA], 33 with RA with
 ringed sideroblasts, and 44 with RA with excess blasts) will be accrued for this study within
 14-22 months.
DISEASE CHARACTERISTICS:

 -  Morphologically confirmed myelodysplastic syndromes (MDS)

 -  Refractory anemia (RA)

 -  RA with ringed sideroblasts

 -  RA with excess blasts

 -  Low, intermediate-1, or intermediate-2 risk by International Prognostic Scoring System
 criteria

 -  MDS secondary to prior chemotherapy and/or radiotherapy for other malignant disorders
 allowed

 -  Must have received prior transfusions of at least 4 units of red blood cells for
 anemia within the past 60 days

 -  Must be concurrently registered on SWOG-S9910 and SWOG-9007

 -  Ineligible for or refused participation in SWOG-S9920 (HLA-identical sibling
 peripheral blood stem cell transplantation)

 PATIENT CHARACTERISTICS:

 Age:

 -  15 and over

 Performance status:

 -  Zubrod 0-2

 Life expectancy:

 -  Not specified

 Hematopoietic:

 -  Not specified

 Hepatic:

 -  Not specified

 Renal:

 -  Not specified

 Other:

 -  No other malignancy within the past 2 years except adequately treated basal cell or
 squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
 stage I or II cancer in complete remission

 -  HIV negative

 -  Not pregnant or nursing

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  See Disease Characteristics

 -  Prior cytokines (e.g., interferon or interleukin), colony-stimulating factors, or
 epoetin alfa allowed

 -  No prior bone marrow or stem cell transplantation

 -  No concurrent growth factors (including epoetin alfa) except filgrastim (G-CSF) or
 sargramostim (GM-CSF) for neutropenia

 Chemotherapy:

 -  See Disease Characteristics

 -  No prior remission induction chemotherapy for MDS

 -  Prior hydroxyurea allowed

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  See Disease Characteristics

 Surgery:

 -  Not specified

 Other:

 -  Prior amifostine allowed

 -  No calcium-channel blockers (diltiazem, nicardipine, or verapamil), antifungals
 (fluconazole, itraconazole, or ketoconazole), antibiotics (clarithromycin or
 erythromycin), or other drugs (bromocriptine or danazol) that would increase
 cyclosporine concentrations for 48 hours before, during, and for 48 hours after
 cyclosporine

 -  No antibiotics (nafcillin or rifampin) or anticonvulsants (carbamazepine,
 phenobarbital, or phenytoin) that would decrease cyclosporine concentrations for 14
 days before and during cyclosporine