Hematological complications in solid organ transplant recipients with telomere biology disorders: a narrative review

TL;DR

This review discusses how telomere biology disorders can lead to hematological complications in solid organ transplant recipients and emphasizes the need for early detection and multidisciplinary care.

Contribution

The paper provides a narrative review on hematological complications in TBD patients undergoing solid organ transplantation and offers expert strategies for their management.

Findings

Short telomere length is linked to end-stage fibrotic lung and liver diseases requiring transplantation.

Hematological complications in TBD patients may arise from both the disorder and immunosuppressive therapy.

Early detection of TBDs through telomere length assessment and genetic testing is recommended for at-risk transplant candidates.

Abstract

Telomeres are repetitive nucleotide sequences at the ends of chromosomes that preserve genomic integrity. Defects in telomere maintenance mechanisms lead to premature telomere shortening, resulting in cellular senescence, apoptosis, and organ dysfunction, collectively termed telomere biology disorders (TBDs). Short telomere length is associated with an increased risk of end-stage fibrotic disease of the lung and/or liver, which may necessitate lung or liver transplantation. Beyond pulmonary and hepatic involvement, TBDs can also affect cardiac and renal function. Importantly, the bone marrow function is often also compromised, which can significantly influence transplant outcomes. Although evidence remains scarce, particularly in non-lung solid organ transplant recipients, post-transplant immunosuppressive therapy, typically including corticosteroids, calcineurin inhibitors, and cell cycle inhibitors, may exacerbate the underlying hematopoietic fragility in TBD patients. Hematological complications may result from both the intrinsic TBD and the additive myelotoxic effects of immunosuppressive agents (e.g., azathioprine, mycophenolate mofetil) or anti-infectious prophylaxis (e.g., trimethoprim-sulfamethoxazole, valganciclovir). Early recognition of TBDs prior to transplantation is essential. Assessment of telomere length and genetic testing should be considered in at-risk candidates, particularly those with early-onset pulmonary fibrosis, unexplained cytopenia, cryptogenic liver disease, or a family history suggestive of TBD. A multidisciplinary approach involving pulmonology, hepatology, hematology, and transplant specialists is crucial to optimize patient selection, perioperative management, and post-transplant care. This review summarizes current knowledge on hematological complications following solid organ transplantation in TBD patients and describes expert-opinion strategies for the pre-transplant evaluation and post-transplant management of these high-risk individuals.

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