Rapid Transformation of Myelodysplastic Neoplasm to Myelodysplasia-related Acute Myeloid Leukemia with Central Nervous System Leukemia in a Young Adult

Myelodysplastic neoplasms (MDSs) are clonal hematopoietic stem cell disorders that progress to acute myeloid leukemia (AML) in 25%-30% of patients, typically over many years. Rapid transformation and central nervous system (CNS) involvement at AML diagnosis are uncommon in adults and confer a poor prognosis. We report a 35-year-old man with MDS who progressed to AML within 8 months and presented with extreme hyperleukocytosis, pulmonary infiltrates, leukemic retinopathy, and acute neuropsychiatric symptoms. Flow cytometry demonstrated nonmonocytic AML with aberrant CD7 expression and co-expression of CD34 and CD123. Next-generation sequencing revealed RUNX1 and ZRSR2 mutations defining AML with myelodysplasia-related features, with DNMT3A and TET2 mutations indicating evolution from an antecedent clone. Brain magnetic resonance imaging showed diffuse pachymeningeal enhancement, and cerebrospinal fluid confirmed CNS leukemia. Despite standard induction and intrathecal chemotherapy, bone marrow assessment demonstrated primary refractory disease. This case highlights aggressive secondary AML with adverse biology, CNS involvement, and induction failure.