Very Late Extramedullary Relapse of Acute Myeloid Leukemia 13 Years After Allogeneic Transplant: A Case Report

Relapse of acute myeloid leukemia (AML) typically occurs within the first 3 years following treatment, with very late relapses being rare and often presenting extramedullary. We report a unique case of extramedullary AML relapse occurring 13 years after allogeneic hematopoietic stem cell transplantation. The patient developed a myelosarcoma, prompting molecular and histological investigation to determine the origin and mutational landscape of the disease. Next-generation sequencing (NGS) was performed on archived bone marrow samples from the initial AML diagnosis in 2007 and on the relapsed tumor tissue from 2021. The 2007 sample contained nine somatic variants, while the 2021 myelosarcoma harbored four variants. Only a single somatic mutation, a frameshift alteration in the HNRNPK gene, located on 9q21, was shared across both timepoints, suggesting a potential founder event and supporting the hypothesis of clonal evolution. Chimerism analysis and histopathological findings confirmed that the relapse originated from the patient rather than from donor-derived hematopoiesis. This case underscores the importance of long-term vigilance in AML survivors, especially in those receiving chronic immunosuppression, as impaired immune surveillance may allow for reemergence of malignant clones. The persistent HNRNPK mutation across both disease phases may point to a rare but critical driver of leukemogenesis and relapse. Our findings highlight the utility of comprehensive molecular profiling in elucidating disease dynamics and informing personalized monitoring strategies.