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To determine the treatment response and disease progression in strictly selected patients with myelodysplastic syndrome undergoing immunosuppressive therapy (IST), patients were required to have an international prostate symptom score (IPSS) score ≤ 1.0 and at least one of the following conditions: (1) expression of the HLA-DR15 allele, (2) bone marrow (BM) cellularity of less than 30%, and (3) abnormal immune index of BM T-lymphocytes.The exclusion criteria were as follows: (1) ≥ 5% marrow myeloblasts, (2) poor karyotype, and (3) diagnosis of concurrent nonhematological malignancy. Patients received antithymocyte globulin followed by cyclosporine A (CsA) or CsA alone for at least 3 months. Seventy-one cases were analyzed. The total response rate was 77.5% (55/71 cases) with 11 complete responses. The response rate was positively correlated with the number of recruitment criteria met. Patients with an abnormal CD8, an abnormal CD4, or both had similar response rates. Patients who responded to treatment had significantly lower Th1 and Tc1 levels after treatment (P< 0.01 andP< 0.001, respectively), and six of eight patients with abnormal chromosomes did not show obviously abnormal clonal expansion when reassessed after IST. During the median observation period of 24 months, only two cases exhibited disease progression. At the median observation of 24 months, 35 of 55 responders (63.6%) maintained a hematological response, and 60 of 71 patients (84.5%) were still alive. The strictly selective use of IST may yield high response rates and can avoid treatment-related acute myeloid leukemia transformation. IST significantly reduces Th1 and Tc1 levels without causing malignant clonal expansion.