Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients

Diamond-Blackfan anemia (DBA) is a constitutional disease characterized by a specific maturation defect in cells of erythroid lineage. We have assembl ed 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 DB A, 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 wa s found significantly and independently associated with older age at presen tation, familial history of DBA, and a normal platelet count at the time of diagnosis. Severe evolution of the disease (transfusion dependence or deat h) was significantly and independently associated with a younger age at pre sentation and with a history of premature birth. In contrast, patients with a familial history of the disease experienced a better outcome. Outcome an alysis revealed the benefit of reassessing steroid responsiveness during th e course of the disease for initially nonresponsive patients. Bone marrow t ransplantation was successful in 11/13 cases; HLA typing of probands and si blings 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 seas onality on incidence of the disease or on malformative status. Similarly, n o parental imprinting effect or anticipation phenomenon could be documented in families with dominant inheritance.