Outcomes and challenges of stem cell transplantation in patients with ribosomopathies

Ribosomopathies are a heterogeneous group of rare inherited disorders caused by defects in ribosome biogenesis or function, leading to bone marrow failure (BMF), congenital anomalies, immune dysfunction, and increased risk of malignancy. Ribosomopathies associated with hematological phenotype include Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), and cartilage-hair hypoplasia (CHH). Allogenic hematopoietic cell transplantation (HCT) remains the only curative treatment for the hematologic manifestations of these conditions, although it does not correct their extra-hematologic features. In SDS, HCT is indicated for progressive bone marrow failure, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or high-risk clonal evolution. Recent insights into TP53-driven leukemogenesis have improved risk stratification and may support earlier transplantation. Nevertheless, role of TP53 monitoring, timing of HCT, cytoreduction before HCT in MDS/AML, and poor outcomes after leukemic transformation remain major challenges. In DBA, HCT is reserved for transfusion dependence, steroid refractoriness/dependence, BMF, immunodeficiency, or clonal evolution. Outcomes have improved substantially, with recent studies demonstrating comparable survival after matched sibling donor (MSD) and matched unrelated donor (MUD) transplantation. Careful management of iron overload and lifelong cancer surveillance are essential components of care. In CHH, HCT is indicated for severe immunodeficiency, transfusion-dependent anemia, and BMF. Across all ribosomopathies, outcomes are most favorable when transplantation is performed before irreversible organ damage or malignant transformation. Advances in molecular monitoring, particularly for clonal evolution, together with emerging gene therapy and gene-editing approaches, are opening new therapeutic perspectives and may eventually provide alternatives to HCT for selected patients.