Biology and Treatment of Hemophagocytic Lymphohistiocytosis

TY - JOUR

T1 - Biology and Treatment of Hemophagocytic Lymphohistiocytosis

AU - Janka-Schaub, Gritta

PY - 2018/12/31

Y1 - 2018/12/31

N2 - Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndromethat occurs at all ages and is characterized by high levels of cytokines,secreted by activated T-lymphocytes and macrophages. All symptoms andlaboratory changes can be explained by organ infiltration by these cells andhypercytokinemia. HLH occurs as an inherited form (genetic, primary HLH)with mutations primarily in the cytotoxic vesicle pathway, and an acquired formthat, in children, is triggered mostly by infections, but also by autoinflammatory/autoimmune diseases, malignancies and metabolic diseases. The pathogenesis ofgenetic forms of HLH can be explained by the inability of cytotoxic cells to induceapoptosis in (infected) target cells and to terminate the immune response forwhich perforin is essential. The pathogenesis of acquired forms is multifactorial,and several factors may have to be present for the development of HLH: e.g.acquired immune defects; stimulation of the innate immune system via tolllikereceptors or danger signals; interference of viruses and tumor cells withcytotoxicity and apoptosis; secretion of cytokines by tumor cells; mutations orsingle nucleotide polymorphisms in genes important for the immune response;heterozygous mutations in HLH-genes; environmental factors. Treatment ofHLH is a balancing act between too little and too much therapy; cytokines haveto be downregulated without destroying all immune defenses. Once HLH iscontrolled, therapy can be ended in acquired cases, whereas genetic cases needhematopoietic stem cell transplantation for cure. Therapy with corticosteroidsand etoposide, as in the international HLH studies, is still the standard of care.New promising drugs are available; clinical trials have to confirm their efficacy.

AB - Hemophagocytic lymphohistocytosis (HLH) is a hyperinflammatory syndromethat occurs at all ages and is characterized by high levels of cytokines,secreted by activated T-lymphocytes and macrophages. All symptoms andlaboratory changes can be explained by organ infiltration by these cells andhypercytokinemia. HLH occurs as an inherited form (genetic, primary HLH)with mutations primarily in the cytotoxic vesicle pathway, and an acquired formthat, in children, is triggered mostly by infections, but also by autoinflammatory/autoimmune diseases, malignancies and metabolic diseases. The pathogenesis ofgenetic forms of HLH can be explained by the inability of cytotoxic cells to induceapoptosis in (infected) target cells and to terminate the immune response forwhich perforin is essential. The pathogenesis of acquired forms is multifactorial,and several factors may have to be present for the development of HLH: e.g.acquired immune defects; stimulation of the innate immune system via tolllikereceptors or danger signals; interference of viruses and tumor cells withcytotoxicity and apoptosis; secretion of cytokines by tumor cells; mutations orsingle nucleotide polymorphisms in genes important for the immune response;heterozygous mutations in HLH-genes; environmental factors. Treatment ofHLH is a balancing act between too little and too much therapy; cytokines haveto be downregulated without destroying all immune defenses. Once HLH iscontrolled, therapy can be ended in acquired cases, whereas genetic cases needhematopoietic stem cell transplantation for cure. Therapy with corticosteroidsand etoposide, as in the international HLH studies, is still the standard of care.New promising drugs are available; clinical trials have to confirm their efficacy.

UR - http://ijbc.ir/article-1-869-en.pdf

M3 - SCORING: Review article

VL - 10

SP - 108

EP - 113

JO - Iran J Blood Cancer

JF - Iran J Blood Cancer

SN - 2008-4595

IS - 4

ER -