Case Report: Fulminant aggressive NK-cell leukemia with hemophagocytic lymphohistiocytosis and multiple organ dysfunction successfully bridged to allogeneic hematopoietic stem cell transplantation
- 1Department of Hematology, the Affiliated Hospital of Southwest Medical University
- 2Stem Cell Immunity and Regeneration Key Laboratory of Luzhou, Southwest Medical University
- 3Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University
Abstract
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.
Related
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BibTeX
@article{li2026case,
title = {{Case Report: Fulminant aggressive NK-cell leukemia with hemophagocytic lymphohistiocytosis and multiple organ dysfunction successfully bridged to allogeneic hematopoietic stem cell transplantation}},
author = {Shutan Li and Chao Fang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1994954},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1994954/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Fulminant aggressive NK-cell leukemia with hemophagocytic lymphohistiocytosis and multiple organ dysfunction successfully bridged to allogeneic hematopoietic stem cell transplantation
AU - Shutan Li
AU - Chao Fang
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1994954
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1994954/full
AB - 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.
SN - 1664-3224
ER -