Supplementary Material for: High-Risk Acute Myeloid Leukemia Developing in a Patient with Recurrent Melanoma: A Case Report

Introduction: Advances in cancer therapeutics have led to an expanding population of cancer survivors, accompanied by an increased recognition of secondary malignancies. A bidirectional relationship between cutaneous melanoma and hematologic malignancies has been described, though acute myeloid leukemia (AML) following melanoma—particularly in the absence of prior chemotherapy or radiation—remains rare. Case Report: A man in his fifties with no significant comorbidities presented with a chronic pigmented lesion on the lower back, confirmed as superficial spreading melanoma (Breslow thickness 3.3 mm, Stage IIIC). He underwent wide local excision with sentinel lymph node biopsy followed by one year of adjuvant BRAF/MEK inhibitor therapy. The patient’s recurrent dermal melanoma was treated with immune checkpoint inhibitors, leading to complete remission. One year after discontinuation of immunotherapy, surveillance imaging revealed recurrent melanoma with concurrent pancytopenia. Bone marrow biopsy established a diagnosis of AML with complex cytogenetics. The patient achieved complete remission following FLAG induction chemotherapy, and concurrent targeted therapy was resumed for melanoma control. Conclusion: This case illustrates a rare occurrence of AML developing after melanoma in a patient without prior exposure to cytotoxic chemotherapy or radiation. Potential contributing mechanisms include shared oncogenic pathways, ultraviolet-induced genomic instability, and immunotherapy-related clonal hematopoietic expansion. These findings emphasize the necessity for continued investigation into the long-term hematologic consequences of immune checkpoint inhibition and the molecular pathways linking solid tumors to myeloid malignancies.