Diseases of Large Granular Lymphocytes

Todd J. Alekshun, MD; Lubomir Sokol, MD, PhD


Cancer Control. 2007;14(2):141-150. 

In This Article

Aggressive NK-Cell Leukemia

Aggressive NK-cell leukemia is a fulminant sCD3– neoplasm with a poor prognosis that is most prevalent in younger patients of Asian descent.[16,66] The median age of patients with this disorder at diagnosis is 39 years, and males and females are usually affected equally.[1] This clinicopathologic entity is recognized by the WHO classification as a distinct neoplasm that constitutes approximately 10% of all LGL lymphoproliferative disorders.[16,57] There is an association between NK-cell leukemia and Epstein-Barr virus (EBV), thereby implicating EBV as a possible etiology in the pathogenesis of this leukemia.[57,67]

This disease presents in an acute manner and manifests with B symptoms, organomegaly, and cytopenias (Fig 1). Disseminated intravascular coagulopathy (DIC) and multiorgan failure can also occur.[57,66]

Neoplastic cells display CD2+CD3–CD56+ immunophenotype with TCR genes in a germinal configuration, along with clonal episomal EBV.[57,66] These leukemic cells usually lack CD57 expression. The most common cytogenetic abnormalities are deletion 6q21-q25 and loss of 17p13.[66,68,69] Analysis of bone marrow will reveal diffuse infiltration with neoplastic cells, and involved organs will demonstrate destructive infiltrates with necrosis.[57]

Standard therapies such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) are ineffective when used to treat aggressive NK-cell leukemia.[70] Intensive ALL-like therapies with CNS prophylaxis should be considered as an initial treatment for aggressive NK-cell leukemia. Consolidation therapy with hematopoietic cell transplantation should also be considered for those patients achieving responses to induction therapy (Fig 3).[71]


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