Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia

Abstract

We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

Results at a single centre of immunosuppression with cyclosporine A in 66 children with aplastic anaemia

“…Unexpectedly, we observed a rather high remission rate and rather short interval to response in patients with SAA (47% and 8 weeks). This differs strikingly from the results of a study by Gluckman et al (1992) comparable with our series in the number of patients included, who reported responses at 3 months in only 11´6% of patients treated with CsA. Most probably this difference is best explained by the fact that, unlike the above-mentioned study where the median interval from diagnosis to treatment was <1 month, in our cohort it was 5 months.…”

“…Although CsA is being used widely as a component in combined immunosupressive therapy, very little is known about the value of long-term therapy with CsA alone. In the only published randomized study aimed at comparing ATG with CsA, most patients not responding to CsA within 3 months were crossed over to ATG therapy and vice versa (Gluckman et al, 1992). Interestingly, in this study 50% of the nonresponders in whom CsA therapy was mistakenly continued remitted later.…”

Relative erythroid hyperplasia in the bone marrow at diagnosis of aplastic anaemia: a predictive marker for a favourable response to cyclosporine therapy

“…This drug reportedly induces remission in 30-40% of patients with AA. A recent controlled study by a French group has revealed that CyA is at least as effective as antithymocyte globulin (ATG), the most suitable therapy for AA (Gluckman et al, 1992). The advantages of CyA include the fact that it can be given on an outpatient basis and it causes fewer sideeffects.…”

Immunosuppressive Therapy for Acute Porphyria: Safety and Efficacy in a Patient with Bone Marrow Failure

“…4 Cyclosporine is an effective drug and is widely administered to prevent graft rejection of solid organ and bone marrow transplants; it has also been successful in the treatment of bone marrow failure disorders. 5,6 Largely based on data from animal models, cyclosporine is thought to precipitate crises in patients with acute porphyria and, therefore, has been considered contraindicated for patients with the disease. 7 Despite this, two published case reports have described the use of cyclosporine in patients with acute intermittent porphyria who underwent kidney transplantation.…”

“…Based on published case reports indicating that cyclosporine can be administered safely after kidney transplantation in patients with acute intermittent porphyria, 8,9 treatment was started with cyclosporine, which has been shown to be an effective therapy for Tcell-mediated bone marrow failure. 5,6 A baseline 24-hour urine porphobilinogen level was established, and the patient received a test dose of oral cyclosporine 50 mg. A repeat porphobilinogen level was obtained 24 hours later. The patient tolerated the test dose with no symptoms or increases in the repeat porphobilinogen level.…”