Pandey Arjun, Mancuso Talia, Velsher Lea, Kennedy James A
Department of Medicine, University of Toronto, Toronto, ON, Canada.
Cancer Genetics and High Risk Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Fam Cancer. 2025 Mar 22;24(2):31. doi: 10.1007/s10689-025-00455-x.
Telomere biology disorders (TBDs) are a group of genetic conditions characterized by defects in telomere maintenance leading to multisystemic organ involvement and a predisposition to hematologic malignancies. The management of patients with TBDs who develop acute myeloid leukemia (AML) presents a significant challenge due to their limited bone marrow reserve and non-hematopoietic organ dysfunction. We present the case of a 45-year-old patient with a previously unrecognized TBD who presented with AML. The patient's history of longstanding cytopenias, idiopathic avascular necrosis, and pulmonary fibrosis were suggestive of a TBD, which was confirmed through telomere length testing and the presence of a TERT variant. Due to his underlying TBD, he was treated with dose-reduced azacitidine and venetoclax, adapting the approach commonly employed in elderly, co-morbid AML patients ineligible for intensive chemotherapy. This resulted in a complete remission with incomplete count recovery that has persisted for greater than 12 months to date. Aside from prolonged myelosuppression, the patient tolerated the regimen well with minimal toxicity. To our knowledge, this is the first report of the successful utilization of azacitidine and venetoclax as an AML treatment modality in TBD patients and underscores the potential of this regimen as an effective non-intensive treatment strategy for high grade myeloid neoplasms arising in the context of inherited bone marrow failure syndromes.
端粒生物学障碍（TBDs）是一组遗传性疾病，其特征是端粒维持存在缺陷，导致多系统器官受累，并易患血液系统恶性肿瘤。由于患有TBDs的患者骨髓储备有限且存在非造血器官功能障碍，因此对发生急性髓系白血病（AML）的TBDs患者进行管理面临重大挑战。我们报告了一例45岁的患者，其患有先前未被识别的TBDs并表现为AML。患者长期血细胞减少、特发性无血管性坏死和肺纤维化病史提示存在TBDs，这通过端粒长度检测和TERT变异的存在得到证实。由于其潜在的TBDs，他接受了剂量降低的阿扎胞苷和维奈克拉治疗，采用了通常用于不符合强化化疗条件的老年合并症AML患者的方法。这导致了完全缓解，但血细胞计数未完全恢复，迄今为止已持续超过12个月。除了长期的骨髓抑制外，患者对该方案耐受性良好，毒性极小。据我们所知，这是首次报道成功将阿扎胞苷和维奈克拉作为TBD患者AML治疗方式的案例，并强调了该方案作为遗传性骨髓衰竭综合征背景下发生的高级别髓系肿瘤有效非强化治疗策略的潜力。
