Bone marrow failure in telomere biology disorders: Current understanding and the emerging landscape of non-transplant therapies.

Telomere biology disorders (TBDs) are a heterogeneous group of inherited systemic diseases caused by pathogenic variants in genes encoding telomerase or proteins involved in telomere maintenance or protection. With very short and/or dysfunctional telomeres, patients with TBD have clinical manifestations clustered in tissues with high rates of cell proliferation. Bone marrow failure (BMF) is the most common hematologic complication of a TBD and can precede the development of more difficult-to-treat malignant transformation. However, not all patients with TBD develop BMF, and some genotype/phenotype correlations are emerging. While allogeneic hematopoietic cell transplant (HCT) is curative for BMF in TBD, toxicities of the conditioning regimen can be detrimental to other organs. Balancing the risk of malignant transformation with HCT toxicity is a core challenge for providers who care for patients with TBD-associated BMF. Herein, we review the clinical presentation, pathophysiology, surveillance, and non-HCT treatment of BMF in TBD, including supportive care, androgens, thrombopoietin receptor agonists, and investigational approaches.