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Diamond Blackfan anemia (DBA) is a rare congenital syndrome presenting primarily as pure red cell aplasia with constitutional abnormalities and cancer predisposition. Established treatment options are corticosteroids, regular erythrocyte transfusions with iron chelation therapy, and hematopoietic stem cell transplantation (HSCT). To date, HSCT is the only definitive curative treatment for the hematological phenotype of DBA, but there is little experience with its use. Given the rarity of the disease and its unique features, an expert panel agreed to draw up a set of recommendations on the use of HSCT in DBA to guide clinical decision-making and practice. The recommendations address indications, pretransplant patient evaluation, donor selection, stem cell sources, conditioning regimens, prophylaxis of rejection and graft versus host disease, and post-transplant follow-up., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond-Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

Diamond Blackfan anaemia (DBA) is a congenital bone marrow failure syndrome characterised by selective red cell hypoplasia. DBA is most often due to heterozygous mutations in ribosomal protein (RP) genes that lead to defects in ribosome biogenesis and function and result in ribosomal stress and p53 activation. The molecular mechanisms underlying this pathology are still poorly understood and studies on patient erythroid cells are hampered by their paucity. Here we report that RP-mutated lymphoblastoid cell lines (LCLs) established from DBA patients show defective rRNA processing and ribosomal stress features such as reduced proliferation, decreased protein synthesis, and activation of p53 and its target p21. These phenotypic alterations were corrected by gene complementation. Our data indicate that DBA LCLs could be a useful model for molecular and pharmacological investigations.

Secondary iron overload is associated with significant mortality and morbidity. Although new, less invasive techniques are becoming available, the most acceptable and readily accessible way to assess iron overload is to measure hepatic iron by liver biopsy. In this study, we report on serial liver biopsies (at least 2) in a cohort of transfusion-dependent patients (49) on long-term desferrioxamine treatment. There was no significant change in liver iron concentrations (LIC) even in the medication-compliant patients, although there was an upward trend (not statistically significant) in the poorly compliant patients. Fibrosis was present in both HCV RNA-positive and -negative patients, but was more common in positive patients and there was also a significant relationship between fibrosis and hepatic iron concentration. Liver iron levels appear to be maintained in patients who are compliant to desferrioxamine treatment, but overall there is little evidence of significant improvement in liver iron in these patients and in the group as a whole.