NK Cells as Possible Prognostic Factor in Childhood Acute Lymphoblastic Leukemia

Deficiency or impaired function natural killer (NK) cells might result in the development of serious infections and promote the development of malignancies. The aim of our study was to assess the prognostic role of NK cell percentage in bone marrow on the day of acute lymphoblastic leukemia (ALL) diagnosis. 84 children (49 males=58%; median age 5 yrs) with ALL were enrolled. The NK cell percentage was assessed using flow cytometry with antibodies against the cluster of differentiation (CD): CD3, CD56, and CD16. We evaluated two groups: group I (NK+), patients with NK cells in the bone marrow (n=74), and group II (NK-), patients without NK cells in the bone marrow (n=10) (cut-off value of negative <1%). In the patients from group I, the prednisone good response on day 8 and the remission on day 15 of treatment were observed significantly more often (p=.01, p=.03). The children from group I had significantly better survival as compared to those from group II (p=.02) (HR 2.59; 95% CI: 1.38-4.85). The presence of NK cells in the bone marrow at diagnosis can be a prognostic factor in children with ALL. The presented results should be the basis for further research

Molecular genetics diversity of primary hemophagocytic lymphohistiocytosis among Polish pediatric patients

Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of life-threatening inflammation caused by an excessive, prolonged and ineffective immune response. An increasing number of HLH cases is recognized in Poland, but the genetic causes of familial HLH (FHL) have not been reported. We investigated the molecular genetics and associated outcomes of pediatric patients who met HLH criteria. We studied 54 patients with HLH, 36 of whom received genetic studies. Twenty-five patients were subjected to direct sequencing of the PRF1, UNC13D, STX11, XIAP and SH2D1A genes. Additionally, 11 patients were subjected to targeted next-generation sequencing. In our study group, 17 patients (31%) were diagnosed with primary HLH, with bi-allelic FHL variants identified in 13 (36%) patients whereas hemizygous changes were identified in 4 patients with X-linked lymphoproliferative diseases. In addition, one patient was diagnosed with X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection and neoplasia due to a hemizygous MAGT1 variant; another newborn was diagnosed with auto-inflammatory syndrome caused by MVK variants. The majority (65%) of FHL patients carried UNC13D pathogenic variants, whereas PRF1 variants occurred in two patients. Novel variants in UNC13D, PRF1 and XIAP were detected. Epstein–Barr virus was the most common trigger noted in 23 (65%) of the patients with secondary HLH. In three patients with secondary HLH, heterozygous variants of FHL genes were found. Overall survival for the entire study group was 74% with a median of 3.6 years of follow-up. Our results highlight the diversity of molecular causes of primary HLH in Poland