Immunologic and clinical effects of repeated blood exchange in familial erythrophagocytic lymphohistiocytosis

Abstract

Depressed cellular immune function and increased susceptibility to infection characterize familial erythrophagocytic lymphohistiocytosis (FEL), a usually fatal autosomal recessive disease. One component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation. We have tested whether repeated plasma or blood exchange would decrease plasma inhibitory activity and improve cellular immune function in FEL. Following this treatment, reduction in plasma inhibitory activity, reversal of depressed antigen-specific lymphocyte proliferative responses and monocyte antibody-dependent cytotoxic function in vitro, and clinical improvement were complete in two and partial in one of three patients studied. Relapse, which was ultimately fatal, was associated with recurrence of the immune defects. These findings suggest that cellular immunodeficiency in FEL is acquired and possibly related to circulating immunosuppressive activity, the removal of which is associated with transient immunologic and clinical recovery.

Localization of a Gene for Familial Hemophagocytic Lymphohistiocytosis at Chromosome 9q21.3-22 by Homozygosity Mapping

“…The x 2 test value obtained (2.76) is compatible, although not conclusive, in this respect. Heterogeneity with respect to cellular immune dysfunction in FHL (Ladisch et al 1982;Stark et al 1987) is consistent with the possibility that multiple defects underlie the disease phenotype. Since the ethnic background of family 5 varied from that of the other families included in the study, it is conceivable that within individual populations defects of different genes predominate among FHL kindreds.…”

“…immune defect in FHL is provided by evidence that allogeneic bone marrow transplantation may be curative in the presence of mixed chimerism, despite limited donor engraftment (Landman-Parker et al 1993) and the occurrence of hemophagocytic disorders secondary to Tlymphoproliferative disorders (Falini et al 1990). Selective deficiency in natural killer cell activity (Ladisch et al 1982;Perez et al 1984) and T-cell cytotoxicity (Arico et al 1988;Egeler et al 1996) is frequently observed, although its relation to the pathogenesis of FHL remains uncertain.…”

Therapeutic plasma exchange in familial hemophagocytic lymphohistiocytosis

“…In addition to the primary immune defects seen with FHL, the exaggerated inflammatory response and hypercytokinemia contribute to the organ injury that may cause the rapid demise of the patient [9]. Repeated plasma exchange has been shown to produce clinical improvement in patients with FHL in whom the therapeutic benefit was attributed to the lowering of the putative plasma suppressor factor described by Ladisch et al [10]. Increasingly, cytokines and chemokines are being shown to cause many of the observed clinical and biochemical features of FHL.…”

Advances in the diagnosis and management of Haemophagocytic Lymphohistiocytosis: A review of literature

“…Etoposide was first reported in 1980 as a treatment for HLH among 3 children (Ambruso et al 1980). Plasma exchange was later attempted with transient resolution of symptoms in few patients (Ladisch et al 1982). A combination therapy including etoposide, steroids, intrathecal methotrexate and cranial radiation therapy in 1985 revealed prolonged remission in patients with FHLH (Fischer et al 1985).…”