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Combined immunosuppressive therapy of patients with aplastic anemia: Efficiency of repeated antithymocytic globulin courses


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Abstract

The efficiency of repeated courses of antithymocytic globulin (ATG) and algorithm thereof in combination with long-term cyclosporin A (CsA) therapy were studied. The incidence and time course of the cell clone characteristic of paroxysmal nocturnal hemoglobinuria (PNH clone) were studied in patients with aplastic anemia (AA) at different stages of immunosuppressive therapy (IST). The therapeutic algorithm used in the study led to positive response in the majority (84.9%) of AA patients. Remission was attained in 76.7% responding patients, complete remission in 76.8% of these. The majority of patients (61.6%) responded to therapy after the first course of ATG. Clinical hematological improvement was attained in 52.8% patients after 3 months of therapy; after 6 months common response was recorded in 83.4% patients. This period (3-6 months after the beginning of IST) should be regarded, in cases without response to ATG course 1, as the optimal for ATG course 2. Course 2 of ATG led to positive response in 16 more patients, that is, 80.2% patients responded to therapy after two ATG courses. Patients with AA not responding to therapy after two courses of ATG 6-9 months after the beginning of treatment could be referred to the group of patients with refractory AA. Overall and uneventful 7-year survival of AA patients after combined 1ST was 89% (95% CI 83-96%) and 93% (95% CI 88-97%), respectively. The PNH clone was detected before 1ST in 20 (61%) of 33 patients with AA. The median of PNH clone for granulocytes was 1.93% (0.1-99.5%). The clone emerged and persisted in 6 (46%) of 13 patients in whom it was detected before 1ST. All six patients responded to 1ST. Seventeen (85%) of 20 AA patients with PNH clone, detected before IST, responded to IST. In the remaining 3 (15%) patients the PNH clone reduced more than 5-fold, up to complete elimination. Of AA patients without PNH clone before therapy, 8 (61%) responded to therapy. Our results confirmed the probability of response to 1ST in AA patients with PNH clone. The results of combined IST in AA patients indicated high efficiency of the protocol including repeated ATG courses and lonc CsA therapy.


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