Favorable outcome in a child with EBV-negative aggressive NK cell leukemia

Abstract

Aggressive natural killer cell leukemia (ANKL) is a rare malignant disorder of mature NK cells frequently associated with Epstein-Barr virus (EBV). This malignancy is typically treated with intensive remission induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). EBV-negative ANKL and childhood ANKL, however, are not well defined and the optimal therapeutic strategy in these cases is poorly understood. Here, we present a unique pediatric EBV-negative ANKL patient who achieved a successful treatment outcome after intensified ALL type chemotherapy without allogeneic HSCT.

EBV-negative aggressive NK-cell leukemia/lymphoma: a clinical and pathological study from a single institution

“…The following antibodies were used to access T and NK cells: CD3 PerCP-Cy5. 5 13 The bioinformatics pipeline produces a list of annotated variants that have a depth of read of at least × 50 (with Phred quality score 430). This pipeline filters out: all variants with frequency 41% reported in 1000Genome, exAC (The Exome Aggregation Consortium), and ESP (Exome Sequencing Project) databases; any variants that are in the UTR or upstream/downstream of the gene; variants with a synonymous coding effect and variants within intronic region, unless they result in splice site mutations.…”

“…To the best of our knowledge, there have been 16 cases reported in the English literature, [2][3][4][5][6][7][8][9] often as single case reports or rare exceptions included in the studies of EBVpositive aggressive NK-cell leukemia/lymphoma. [2][3][4][5][6][7][8] A recent study of a series of seven cases has shown that the EBV-negative aggressive NK-cell leukemia/ lymphoma is indistinguishable clinically and pathologically from EBV-positive counterpart, 9 in contrast to some earlier reports suggesting that patients with EBV-negative aggressive NK-cell leukemia/lymphoma have a less aggressive clinical course and more favorable response to treatment. 2,5,7 Most of the studies on the pathogenesis of NK/ T-cell lymphomas were on extranodal NK/T-cell lymphoma, nasal type, or its cell line derivative, with very limited information on aggressive NK-cell leukemia/lymphoma.…”

“…[2][3][4][5][6][7][8] A recent study of a series of seven cases has shown that the EBV-negative aggressive NK-cell leukemia/ lymphoma is indistinguishable clinically and pathologically from EBV-positive counterpart, 9 in contrast to some earlier reports suggesting that patients with EBV-negative aggressive NK-cell leukemia/lymphoma have a less aggressive clinical course and more favorable response to treatment. 2,5,7 Most of the studies on the pathogenesis of NK/ T-cell lymphomas were on extranodal NK/T-cell lymphoma, nasal type, or its cell line derivative, with very limited information on aggressive NK-cell leukemia/lymphoma. [10][11][12] Gene expression profiling of EBV-associated nasal-type NK/T-cell lymphoma identified a number of genes differentially expressed in the tumor cells, one of which encodes enhancer of zeste homolog 2 (EZH2), a trimethylated histone H3 lysine residue 27 (H3K27)-specific histone methyltransferase.…”

EBV-negative Aggressive NK-cell Leukemia/Lymphoma

“…Since its description by Fernandez et al in 1986 14 , sporadic EBV negative ANKL cases have been reported . EBV-negativity has been speculated to correlate with a less aggressive clinical outcome 15,11 . However, the rarity of the reported cases precludes firm conclusions.…”

“…However, occasional reports of EBV-negative ANKL have been described 1, 5, 6, 9–11 and a slightly better outcome observed was attributed to an EBV-negative status 6, 11 . Nevertheless, the limited number of the cases reported hampers definitive conclusions.…”