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

Abstract

Introduction: Ring chromosomes (RC) are acquired circular structural abnormalities associated with gain or loss of genetic material, which are thought to be associated with inferior outcomes of patients with myeloid neoplasms (MN). The responses of patients with MN and RC to the standard therapeutic options have not been reported previously.

Methods: We analyzed the demographics and outcomes of 31 consecutive patients with MN and RC and compared median overall survival (mOS) 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 did not receive prior radiation or chemotherapy. Patients who received supportive care had a shorter mOS (p = 0.001), but none of the therapeutic interventions were associated with further improvement in prolonging mOS (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 RC.

Conclusion: These findings indicate the patients with MN and RC have especially poor outcomes, and that effective treatment strategies remain an unmet need.