Ring Chromosomes in Patients with Myeloid Neoplasms Are Associated with a Poor Response to Therapy

髓系肿瘤患者体内的环状染色体与治疗反应不良相关

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Abstract

INTRODUCTION: Ring chromosomes (RCs) are acquired circular structural abnormalities associated with gain or loss of genetic material, which are thought to be associated with inferior outcomes in patients with myeloid neoplasms (MNs). Responses of patients with MN and RC to the standard therapeutic options have not been previously reported. METHODS: We analyzed the demographics and outcomes of 31 consecutive patients with an MN and RC, comparing overall survival (OS) and progression-free survival (PFS) of patients who received supportive care (n = 9), cytotoxic chemotherapeutic options (n = 3), hypomethylating agents (HMA) alone (n = 6), or HMA in combination with venetoclax (n = 13). RESULTS: Over 60% of all patients with RC had either a TP53 mutation, loss of 17p, or both. Interestingly, 22/31 (71%) of patients had not received prior radiation or chemotherapy. Patients who received supportive care had a shorter OS (p = 0.001), but none of the therapeutic interventions were associated with further improvement in prolonging OS (p = 0.86) or PFS. The presence of a complex karyotype, TP53 mutations/loss of TP53, or a treatment-related MN was not independently associated with an inferior OS in MN patients with RCs. CONCLUSION: These findings indicate that patients with MN and RC have especially poor outcomes and that effective treatment strategies remain an unmet need.

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