Therapy-related myeloid neoplasms following treatment for high-risk gestational trophoblastic neoplasia: a case series and retrospective analysis.
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BACKGROUND: Therapy-related myeloid neoplasms (t-MNs), including therapy-related myelodysplastic syndrome and therapy-related acute myeloid leukemia, are rare but severe late complications of cytotoxic chemotherapy. This study aimed to identify the occurrence of t-MNs in patients with high-risk gestational trophoblastic neoplasia (GTN) treated at our institution. METHODS: A retrospective review was conducted in 47 patients with high-risk GTN treated between 1990 and 2023. Clinical data included age, antecedent pregnancy, International Federation of Gynecology and Obstetrics stage, World Health Organization prognostic score, chemotherapy regimen, cumulative etoposide dose, and outcomes. Patients who developed t-MN were compared with those who did not. RESULTS: Among the 47 patients, 34 (72%) achieved cure without relapse, 6 (13%) achieved cure following relapse, and 7 (15%) did not achieve cure. Four patients (8.5%) developed t-MN after prolonged chemotherapy. The latency from initiation of GTN treatment to t-MN onset ranged from 3 to 5 years, whereas the interval from the last chemotherapy administration to diagnosis ranged from immediately after treatment completion to 20 months. All four patients received multi-agent, etoposide-containing regimens with cumulative doses ≥ 6,000 mg/m2. Cytogenetic and molecular analyses revealed KMT2A (formerly MLL) rearrangements and IDH1/2 mutations. Despite allogeneic hematopoietic stem cell transplantation, clinical outcomes were unfavorable, and all patients ultimately died of t-MN or associated complications. CONCLUSION: Although combination chemotherapy remains essential for high-risk GTN, exposure to high cumulative doses of etoposide confers a risk of secondary t-MNs. Long-term hematologic surveillance and less leukemogenic strategies are warranted.