Abstract

Background: DBA is a rare genetic disorder characterized by faulty ribosome biogenesis, leading to pro-apoptotic erythropoiesis and red cell failure. The Diamond Blackfan Anemia Registry (DBAR) was established in 1993 to provide a robust database for investigating the biology and epidemiology of DBA. The DBAR defines remission in DBA as independence from red cell transfusion or corticosteroid therapy for greater than 6 months. An understanding of factors influencing DBA remission may provide insights into the pathophysiology of DBA and ultimately can lead to improved treatment options.

Method: Patients were enrolled in the DBAR with informed consent. Patients who met the remission criteria for this study were evaluated. Patients who reported a remission were contacted and completed a “remission questionnaire”; further information was obtained from the patients’ physicians and verified, where possible, from medical records.

Results: Of 555 patients enrolled in the DBAR, 67 patients have experienced a remission (actuarial likelihood approximately 20%). The male: female ratio for remission patients vs. the total DBAR population is 1:0.97 vs. 1:1.03, respectively. Sixty-four percent of patients have congenital anomalies, compared to 47% in the total population; the difference is not statistically significant. All categories of congenital anomalies (e.g. orofacial, cardiac, renal, skeletal, etc.) are represented in the remission population. The median age at diagnosis is 2.9 months (range, 0 to 14.9 years). The majority of patients were started on 2mg/kg/day of prednisone or methylprednisolone at a median age of 3.6 months (range, 4 days to 15.2 years). Sixty-six percent entered remission while on steroid therapy. The median total duration on steroids was 36 months (range, 1 month to 37.6 years) and the median duration from start of steroids to beginning of taper was 3.6 months (range, 1 month to 4.6 years). Seventeen percent of patients went into remission with less than one year of steroids and 55% were in remission within 5 years of start of steroids. Fifteen percent remitted while receiving chronic transfusion therapy. Six percent never received steroids prior to remission and 7.5% of remitters initially responded to steroids but became steroid refractory prior to remission. Median duration of treatment to remission and duration of remission were 16 months (range, 6 months to 38.2 years) and 14 years (range, 1 to 46.8 years) respectively. The median age of remission was 6.4 years (range, 0.8 to 39 years); males 6.5 years (range, 0.8 to 39 years) and females 6.3 years (range, 1.1 to 26 years). Of note, remissions were observed in DBA patients or in affected family members of probands with mutations in 4 of the 6 genes (RPS 19, RPS 24, RPL35a, and RPS11) known to be mutated in DBA as well as in those with no known mutation, suggesting that remission is not restricted to a particular genotype. Additional patients are being genotyped.

Conclusion: Remission in patients with DBA is not an uncommon event. Steroid responsiveness is not a prerequisite for remission. There is no obvious phenotypic or genotypic difference between remission and non-remission patients. The expression of a remission phenotype within multiplex families is quite variable. We conclude that remission is not restricted to a particular phenotype or genotype and that the likelihood of remission is influenced by unknown modifier genes and/or epigenetic factors.

Disclosures: No relevant conflicts of interest to declare.

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