Showing papers on "Hemophagocytic lymphohistiocytosis published in 1996"

Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society.

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare, often fatal, disease of early infancy. The diagnosis of HLH is frequently delayed or made at autopsy because no genetic or biologic marker has been identified. To improve the classification and treatment of HLH, the Histiocyte Society has established an 'International Registry for HLH'. Data collected included family history, clinical and laboratory features at the onset of illness, and treatment outcome. Stringent diagnostic criteria (ie fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemia, and hemophagocytosis without evidence of malignancy) were used for patient selection. One hundred and twenty-two patients (61 males, 61 females) were enrolled from 17 centers in 11 countries. The rate of parental consanguinity was 24%. A positive family history was reported in 49% of cases including two pairs of affected male twins. The median age at disease onset was 2.9 months, with no difference between familial and sporadic cases. Age at onset was similar in affected sibs from 10 of 14 families, but in four up to 3-year differences were observed. Hemophagocytosis was present at diagnosis in 75%. An associated infection (usually by common viral pathogens) was reported in 50 of the 122 (41%) cases, of which 25 had familial disease. Natural killer activity was impaired in 36 of 37 patients studied. Chromosome analysis was normal in all tested patients. A decreased frequency of HLA-B7 and B8 alleles and increased frequency of HLA-B21 and DQ3 were observed. The estimated 5-year survival (SE) was 21% (18.7) for all patients. It was 66% (37.8) for patients who received allogeneic bone marrow transplant and 10.1% (9.6) for patients treated with chemotherapy alone (P = 0.0001). None of the previously proposed prognostic indicators (age, associated infection, cerebrospinal fluid pleocytosis, family history) correlated with treatment outcome.

Characteristic immune abnormalities in hemophagocytic lymphohistiocytosis

Abstract: Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by fever, hepatosplenomegaly, pancytopenia, and infiltration of vital organs by non-Langerhans histiocytes and is rapidly fatal without early diagnosis and institution of therapy. Immune dysregulation is thought to be responsible for the disease. Patients and Methods: Extensive immune evaluation was performed on 13 consecutive patients diagnosed with HLH over a 4-year period to characterize existing immunologic abnormalities in order to improve early diagnosis. Evaluation included quantitative immunoglobulins, immunophenotyping, mitogen-induced lymphoproliferation, natural killer (NK) cell function, and cytotoxic T cell lymphocytolysis (CTL). Results: Immunoglobulin levels showed no consistent abnormality. Immunophenotyping showed an absolute decrease in number of B cells but normal numbers and proportional distribution of T cell subsets and NK cells. Most patients demonstrated decreased proliferative responses to mitogens (10/13) and severely decreased to absent T cell cytotoxicity (11/12) and NK cytotoxic function (13/13). Conclusions: Our results show that while humoral immunity is essentially intact, cellular immune function is significantly impaired in the vast majority of patients with HLH. The coincident finding of profoundly decreased T cell cytotoxicity along with absent NK cytotoxicity suggests that patients with active HLH may have global cytotoxic dysfunction. Since the majority of our patients were studied prior to starting therapy, we feel that these findings reflect the pathophysiologic process and are not therapy related. Unclear from the present work is whether these findings represent primary or secondary dysfunction. We conclude from these studies that profoundly decreased CTL function and absence ofNK cell function are characteristic immunologic features of HLH and may serve as additional laboratory data, in conjunction with currently proposed diagnostic guidelines, to support a diagnosis of HLH.

Elevated circulating levels of interleukin‐1 receptor antagonist but not IL‐1 agonists in hemophagocytic lymphohistiocytosis

Abstract: The familial form of hemophagocytic lymphohistiocytosis (HLH) is an inherited disease with disturbed immunomodulation and characterized by fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and coagulopathy, i.e., findings which are similar to many of the reported biological effects of the inflammatory cytokines. Due to the previously shown hypercytokinemia in active HLH with elevated levels of interleukin (IL)-6, tumor necrosis factor-alpha, and interferon-gamma, it has been suggested that cytokine dysregulation may be of pathophysiological importance. Here we have assayed the serum levels of the members of the IL-1 ligand family, the two agonists IL-1 alpha and IL-1 beta and the antagonist IL-1 receptor antagonist (IL-1ra), in nine children with HLH and cerebrospinal fluid (CSF) specimens from four children. Serum IL-1ra was elevated in all patients with active disease to a degree which correlated well with disease activity. Furthermore, the levels decreased day by day during treatment of a patient who suffered a relapse. Moreover, high levels of IL-1ra were also detected in CSF during active disease. However, IL-1 beta levels were all within normal limits and circulating IL-1 alpha levels were normal in all but two patients.

Infection-Associated Hemophagocytic Syndrome Complicated by Infectious Lymphoproliferation: A Case Report

Abstract: The case of a 7-year-old boy with virus-associated hemophagocytic syndrome (VAHS) and serologically proven parvovirus B-19 infection is described. The patient with VAHS presented with fever, hepatosplenomegaly, pancytopenia, and hyperlipidemia type IV. After induction therapy with VP-16 and prednisone, partial remission was achieved. Despite maintenance therapy, reinductions, and the addition of cyclosporine A for 3 months, several relapses occurred. The therapy was stopped because of life-threatening complications (Klebsiella sepsis, neutropenic enterocolitis, and stercoral peritonitis). The complications were treated successfully. The patient status was stabilized after splenectomy. However, hepatomegaly progressed slowly and the hyperlipidemia endured. Ten months after the diagnosis leukocytosis with absolute T lymphocytosis appeared. Reactivation of VAHS was suspected and intravenous immunoglobin and then antilymphocyte immunoglobulin ALG therapy were started. The resultant decrease in leukocytosis was prompt, but lymphopenia did not occur. Virostatic treatment with foscarnet was introduced based on human herpesvirus-6 seroconversion. Twenty-six months after the diagnosis, the patient is well, without any sign of VAHS or lymphoproliferation.