Case Report: Fulminant aggressive NK-cell leukemia with hemophagocytic lymphohistiocytosis and multiple organ dysfunction successfully bridged to allogeneic hematopoietic stem cell transplantation

Aggressive natural killer-cell leukemia (ANKL) is an exceedingly rare and rapidly fatal malignancy of mature NK cells, frequently associated with Epstein-Barr virus (EBV), and its diagnosis is often complicated by hemophagocytic lymphohistiocytosis (HLH) that can obscure the underlying malignancy and delay therapy. We report the case of a 28-year-old male who presented with high-grade fever, pancytopenia, hepatosplenomegaly, and disseminated intravascular coagulation (DIC), with laboratory findings confirming HLH; bone marrow examination and flow cytometry identified an aberrant NK-cell population with a characteristic immunophenotype (CD2+, sCD3−, CD56+, CD16−), establishing the diagnosis of ANKL, and next-generation sequencing revealed mutations in JAK1, ASXL1, KMT2D, and FAS. The patient received sequential multimodal therapy, including a single administration of etoposide plus dexamethasone for initial HLH control, followed by two cycles of P-Gemox (pegaspargase, gemcitabine, oxaliplatin), and subsequently underwent successful haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sibling, followed by one year of chidamide maintenance. Complete remission was achieved after P-Gemox induction and has been maintained with full donor chimerism at 35 months of follow-up. This case highlights that timely diagnosis and a sequential, multimodal treatment strategy can successfully bridge ANKL patients presenting with HLH to curative allo-HSCT. P-Gemox appeared to be well tolerated in our patient, and these findings underscore the critical importance of early recognition and prompt treatment initiation for improving outcomes in this devastating disease.