Identification of New Prognosis Factors from the Clinical and Epidemiologic Analysis of a Registry of 229 Diamond-Blackfan Anemia Patients

Abstract

Diamond-Blackfan anemia (DBA) is a constitutional disease characterized by a specific maturation defect in cells of erythroid lineage. We have assembled a registry of 229 DBA patients, which includes 151 patients from France, 70 from Germany, and eight from other countries. Presence of malformations was significantly and independently associated with familial history of DBA, short stature at presentation (before any steroid therapy), and absence of hypotrophy at birth. Two hundred twenty-two patients were available for long-term follow-up analysis (median, 111.5 mo). Of these individuals, 62.6% initially responded to steroid therapy. Initial steroid responsiveness was found significantly and independently associated with older age at presentation, familial history of DBA, and a normal platelet count at the time of diagnosis. Severe evolution of the disease (transfusion dependence or death) was significantly and independently associated with a younger age at presentation and with a history of premature birth. In contrast, patients with a familial history of the disease experienced a better outcome. Outcome analysis revealed the benefit of reassessing steroid responsiveness during the course of the disease for initially nonresponsive patients. Bone marrow transplantation was successful in 11/13 cases; HLA typing of probands and siblings should be performed early if patients are transfusion dependent, and cord blood should be preserved. Incidence of DBA (assessed for France over a 13-y period) is 7.3 cases per million live births without effect of seasonality on incidence of the disease or on malformative status. Similarly, no parental imprinting effect or anticipation phenomenon could be documented in families with dominant inheritance.

RPS19 mutations in patients with Diamond-Blackfan anemia

“…While this is still true, it is now clear that poor steroid sensitivity is common to all patients with RPS19 alterations. Their response to the first steroid course is 46% (42/91 patients whose data were available, two of them showing a partial response) compared with more than 70% of the overall DBA population [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Over the last 10 years, clinical data from the main European and North American DBA registries have been published [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006].…”

“…Their response to the first steroid course is 46% (42/91 patients whose data were available, two of them showing a partial response) compared with more than 70% of the overall DBA population [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Over the last 10 years, clinical data from the main European and North American DBA registries have been published [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. Our review of these reports with data for over 800 DBA patients has shown that those with RPS19 mutations display a significantly lower sensitivity to steroids (po0.0001) and are significantly more likely to become transfusion dependent or require SCT (po0.0001) ( Table 2).…”

“…a Complete clinical data were not available for all patients. The range refers to di¡erent values from the di¡erent registries [Ball et al, 1996;Willig et al,1999b;Campagnoli et al, 2004;Lipton et al, 2006]. c Mean age in RPS19 mutated patients 2.573 months (mean age in patients with no RPS19 mutation from the Italian Registry, 5.978 months).…”

“…If our data are confirmed, this definition will be not only important for diagnosis, but may also be relevant for prognosis and perhaps for patienttailored treatment. Ã DBA patient data from the DBA Registries of the United States/Canada, France/Germany, UK, and Italy [Ball et al,1996;Willig et al,1999b;Campagnoli et al, 2004;Lipton et al, 2006]. a Complete clinical data were not available for all patients.…”

“…DBA is primarily treated with steroids and more than 70% of patients respond to the first course [Ball et al, 1996;Willig et al, 1999b;Campagnoli et al, 2004;Lipton et al, 2006]. The longterm response, however, is extremely variable: some patients go into remission, others develop steroid-resistance.…”