Diamond-Blackfan Anemia and Cyclosporine Therapy Revisited

Abstract

A girl with Diamond-Blackfan anemia diagnosed in infancy started cyclosporine A (CSA) therapy at 9 years and 8 months of age after experiencing unacceptable side effects while receiving prednisone. Since then, she has been followed-up for more than 4 years. She exhibited a dramatic response to CSA, with weaning and then cessation of steroid therapy after 5 months. She has remained transfusion-independent. Attempts to discontinue CSA therapy have been unsuccessful. Relapse of the anemia has occurred in the context of viral infections with missed CSA doses. The major clinical problem during treatment has been recurrent oral aphthous ulceration, which responds to topical therapy. She is currently maintained on CSA 100 mg twice daily with a hemoglobin of 10.2 g/dL and a reticulocyte count of 1.6%. A trial of CSA therapy should be considered in patients with Diamond-Blackfan anemia in whom steroid therapy has failed before a transfusion program is instituted or alternative donor stem cell transplantation is entertained.

Study of 22 Egyptian Patients With Diamond-Blackfan Anemia, Corticosteroids, and Cyclosporin Therapy Results

“…Risks of transfusion therapy, such as iron overload, have rekindled interest in alternative treatment modalities. 12 Similarly, in our studied cases, corticosteroid therapy fails in 45.5% of cases. All corticosteroid nonresponders received periodic prednisone trials over variable courses (ranging from 1-7 courses) to hopefully http://www.pediatrics.org/cgi/content/full/110/4/e44achieve the response even at a later date.…”

“…14 An incidence of 4 to 5 cases per million live births was reported. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Although most cases are sporadic, inheritance is observed in 10% of patients, with a dominant or, more rarely, recessive pattern. 8 -16 Abnormalities in chromosome 19q13.2 have been identified in 25% of familial and sporadic cases of DBA, in another subset of patients another locus on chromosome 8p has identified in association with DBA.…”

“…4 -10 Studies suggest a role for T-cell suppression of erythroid stem cells in this disease, making an agent such as CSA a logical therapeutic choice. 11,12 Also, CSA has been shown to inhibit apoptosis by modulation of Fas and through downregulation of ␥-interferon production, which may play a role in the pathophysiology of this disease. 12 In our center, 8 patients received CSA therapy (Table 1).…”

“…Reghavacher 4 reported that CSA is effective in the treatment of steroid resistant acquired pure red cell aplasias in ϳ65% of cases. Alessandri et al 12 reported that 18.2% of patients with DBA from different studies have experienced a sustained remission or partial response to CSA. Although long-term spontaneous remission occurs in ϳ20% 20 of DBA patients, our responders to CSA were on steroid therapy for at least 2 courses and did not improve, yet did improve after CSA therapy.…”

“…[7][8][9][10] Cyclosporin-A (CSA) has been reported in few patients by several investigators to produce remission in patients with DBA in whom standard prednisone doses had failed. 11,12 …”