Can targeted therapy improve outcome in Epstein–Barr virus-negative aggressive natural killer cell leukemia: A case report

Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy, with only a few cases reported in the literature. The overall median survival is estimated to be less than 2 months. Moreover, Epstein–Barr virus (EBV)-negative ANKL is a rarity, with only a few being EBV-negative. We present a 27-year-old male with pancytopenia, massive splenomegaly, and no lymphadenopathy. Bone marrow (BM) aspirate flow cytometry revealed abnormal lymphocytes showing moderate expression of CD56, CD16, CD38, CD2, and CD45, dim expression of CD7 and CD117, and variable cytoplasmic CD3 and were negative for immaturity markers and other T lymphocytic, myeloid, and plasmacytoid dendritic cell markers. The BM biopsy revealed negative terminal deoxynucleotidyl transferase, confirming the diagnosis of ANKL. EBV was negative; hence, the final diagnosis of EBV-negative ANKL was offered. The patient had a progressive course despite two cycles of modified SMILE regimen and CHOP. The addition of daratumumab (anti-CD38 monoclonal antibody) to CHOP resulted in disease remission. The patient has survived for more than 18 months after diagnosis and is presently on follow-up on maintenance daratumumab, awaiting an allogenic stem cell transplant. This article aims to report rare refractory EBV-negative ANKL patients successfully managed with an unconventional regimen; hence, further studies are warranted for targeted therapy in fulminant diseases like ANKL.