Therapy-related acute myeloid leukemia following successful treatment of high-risk neuroblastoma in a pediatric patient: a case report and insights into late complications.

BACKGROUND

Neuroblastoma is the most common extracranial solid tumor in childhood. With advances in risk-adapted multimodal therapy, survival outcomes for high-risk neuroblastoma have improved substantially. However, prolonged survival has been accompanied by an increasing incidence of therapy-related second malignant neoplasms, which represent a serious late complication and a growing clinical challenge.

CASE PRESENTATION: We report a rare case of an extremely early-onset secondary malignancy in a young child treated for high-risk neuroblastoma. A 3-year-and-4-month-old girl achieved complete remission after intensive multimodal therapy for stage IV high-risk neuroblastoma. Remarkably, only one month after completion of treatment, she developed therapy-related acute myelomonocytic leukemia (AML, FAB M4 subtype). Bone marrow evaluation revealed high-risk molecular features, including a t(9;11)(p21;q23) translocation resulting in a KMT2A-MLLT3 (MLL/AF9) fusion and concomitant EVI1 overexpression.

RESULTS

The patient was treated with intensive AML-directed chemotherapy followed by allogeneic hematopoietic stem cell transplantation. She achieved complete hematologic and molecular remission, with sustained negativity of minimal residual disease. At the last follow-up in July 2025, she remained in continuous remission for 51 months and had returned to normal school life.

CONCLUSION

This case highlights an exceptionally short latency of therapy-related AML as a second malignant neoplasm following modern intensive treatment for high-risk neuroblastoma. It underscores the need for heightened vigilance for secondary malignancies even during the early post-treatment period and emphasizes the importance of long-term surveillance strategies in neuroblastoma survivors. Early recognition and timely allogeneic transplantation may offer curative potential in selected high-risk cases. Despite the overall poor prognosis associated with therapy-related acute myeloid leukemia (t-AML), this patient achieved long-term survival following allogeneic hematopoietic stem cell transplantation, highlighting the potential for successful outcomes even in high-risk cases.