Refractory Acute Myeloid Leukemia following Extended Peptide Receptor Radionuclide Therapy for Well-Differentiated...

Peptide receptor radionuclide therapy (PRRT) using ¹⁷⁷Lu-DOTATATE is an established treatment for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. However, the incidence and risk profile of therapy-related myeloid neoplasms following extended ¹⁷⁷Lu-DOTATATE exposure particularly beyond the standard four-cycle regimen remain poorly defined.

We report a 49-year-old woman with a well-differentiated jejunal neuroendocrine tumor with hepatic and peritoneal metastases who underwent bowel resection and limited hepatic metastatectomy, followed by long-acting somatostatin analog therapy and subsequent enrollment in a provincial PRRT clinical trial. She received 12 cycles of 177Lu-DOTATATE over 5 years (4 induction, 8 maintenance), without prior cytotoxic chemotherapy or external-beam radiotherapy, achieving durable biochemical and radiologic disease stability with minimal early toxicity. In late 2023, she developed progressive pancytopenia. Bone marrow examination in September 2024 revealed high-risk therapy-related acute myeloid leukemia (AML) characterized by inv(3)(q21q26.2), monosomy 7, complex cytogenetics, and a KRAS mutation. Her leukemia was refractory to intensive induction and subsequent lower-intensity therapy. She died on January 13, 2025, from progressive refractory AML with multiorgan dysfunction and central nervous system involvement.

This case highlights a rare but life-threatening late hematologic toxicity associated with extended ¹⁷⁷Lu-DOTATATE exposure and underscores the importance of long-term hematologic surveillance and critical evaluation of PRRT maintenance strategies beyond the standard four-cycle protocol.