2026-07-09 | [Inherited bone marrow failure syndromes].
Diamond-Blackfan anemia (DBA) is a classic example of an inherited bone marrow failure syndrome in the category of erythrocyte diseases. DBA mainly occurs due to ribosome dysfunction. In the peripheral blood, reticulocytes are reduced, and in the bone marrow, only erythroid cells are markedly reduced. DBA primarily develops in infants and is often caused by heterozygous allele mutations in ribosomal protein genes. Activation of p53, translation dysfunction, inflammatory signals, and imbalance of hemoglobin/heme synthesis have been shown to contribute to impaired erythropoiesis and decreased red blood cell production. Patients with DBA are primarily treated with steroids; however, half of these patients eventually become unresponsive to long-term steroid treatment and become transfusion-dependent. Hematopoietic cell transplantation is currently the only curative treatment. Recent advances in gene therapy using lentiviral vectors have shown potential in promoting normal hematopoiesis in the treatment of RPS19-deficient DBA.
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2026-06-30 | Factors determining successful allogeneic hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes
Introduction. Inherited bone marrow failure syndromes (IBMFS) constitute a heterogeneous group of rare genetic disorders associated with impaired hematopoiesis, congenital anomalies, and a high risk of transformation to myelodysplastic syndrome and acute myeloid leukemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for IBMFS. Aim: to identify factors determining the efficacy of allo-HSCT in pediatric patients with IBMFS. Materials and methods. This study analyzed data from 61 patients with IBMFS who had undergone allo-HSCT between 2005 and 2025 at the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation. Results. The median follow-up was 24 months. The overall survival (OS) at 1, 3, and 5 years post-transplantation was 88%, 85%, and 81%, respectively. The lowest 5-year OS was observed in the Fanconi anemia (47%) and Diamond–Blackfan anemia (86%) groups, whereas in the patients with other IBMFS the 5-year OS reached 100% (p = 0.003). Factors associated with improved survival included age younger than 5 years at transplantation (100% vs. 68%; p = 0.009), the use of myeloablative conditioning regimens (100% vs. 64.5%; p = 0.002), the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis (100% vs. 67%; p = 0.02), and successful engraftment (88% vs. 33%; p = 0.002). GVHD prophylaxis regimens without calcineurin inhibitors were associated with a lower incidence of grade II–IV acute GVHD (11% vs. 44%; p = 0.03) and a reduced need for switching immunosuppression (5% vs. 35%; p = 0.02). Donor type and degree of HLA matching did not significantly affect survival. Conclusion. Allo-HSCT is a highly effective treatment for children with IBMFS, providing a 5-year OS of 81%. The best outcomes are achieved with allo-HSCT performed at an early age (under 5 years), the use of myeloablative conditioning regimens (when not contraindicated), and with the addition of PTCy to GVHD prophylaxis. The lowest survival was observed in the patients with Fanconi anemia, highlighting the need for further refinement of treatment protocols for this patient group. PTCy-based GVHD prophylaxis regimens without calcineurin inhibitors reduce the incidence of acute GVHD and improve the tolerability of immunosuppression.
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2026-06-30 | Recovery of erythropoiesis in Diamond–Blackfan anemia using eltrombopag in a cellular model: interim study results
Introduction. Diamond–Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome classified as a ribosomopathy and characterized by selective aplasia of the erythroid lineage. Despite advances in understanding its pathogenesis, treatment options are still limited, and a significant proportion of patients remain transfusion-dependent. Aim: to evaluate the effect of eltrombopag on the colony-forming potential of bone marrow erythroid progenitors in DBA patients in vitro. Materials and methods. The study included 10 patients with genetically confirmed DBA and 7 healthy donors. Bone marrow mononuclear cells were cultured in a methylcellulose medium supplemented with eltrombopag at concentrations of 13 and 26 μg/mL. Results. In vitro, the addition of eltrombopag to bone marrow cell cultures from the patients with DBA resulted in a significant increase in the number of erythroid colonies compared to control cultures without the drug. For early erythroid progenitors, a statistically significant increase in the number of colonies was observed. Conclusion. These interim results suggest that eltrombopag may be considered a potential stimulator of erythropoiesis in DBA and support the need for further research in larger cohorts in order to clarify the clinical significance of the observed effects.
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