Early Diagnosis and Treatment of the Patients with Acquired Hemophagocytic Lymphohistiocytosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3552-3552
Author(s):  
Zhao Wang ◽  
Yini Wang ◽  
Cuicui Feng ◽  
Liping Tian
Keyword(s):  
Early Diagnosis ◽  
Diagnostic Criteria ◽  
Peripheral Blood ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Nk Cell ◽  
Clinical Symptoms ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Final Diagnosis ◽  
Nk Cell Activity

Abstract Acquired hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition characterized by uncontroling hyperinflammation on the basis of various infection, tumor and inherited immune deficiency. Awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time. In this study, we reviewed 57 suspected HLH patients from March 2006 to June 2008. 25 healthy subjects were enrolled in the study as control. NK cell activity in peripheral blood was tested by a released LDH assay. Meanwhile, solution interleukin-2 receptor (sCD25) was examined with ELISA double antibody sandwich assay. The level of glycosylated ferritin was also detected and the ratio of glycosylated ferritin to ferritin was determined. 41 out of 57 patients were definitely diagnosed according to HLH-2004 diagnostic criteria in this study and 16 patients were excluded. We found that the level of NK cell activity and the ratio of glycosylated ferritin in the all 41 final diagnozed HLH patients were significantly lower than those in the 16 excluded patients and 25 healthy control subjects (p<0.01). Meanwhile, the level of sCD25 in peripheral blood was much higher in all the 41 HLH patients than that in the excluded and healthy people (p<0.05). We compared the coincidence of each diagnostic index in the 41 HLH patients before and after final diagnosis. It was found that 100% patients had abnormal expression on NK cell activity, sCD25 and glycosylated ferritin in the early disease. The three diagnostic indexes were more sensitive and specific than other indexes, such as fever, hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypo-fibrinogenemia. 41 diagnosed patients received the regimen containing methylprednisolone and immunoglobulin, with or without fludarabine, 26 out of 41 were markedly improved after treatment, 10 out of 41 were exacerbated, and other 5 patients gave up treatment. It is concluded that detection of NK cell activity, sCD25 and glycosylated ferritin may play a very important role in the early diagnosis of HLH. Our data also suggest that fludarabine combined with methylprednisolone and immunoglobulin (FDIg) may provide a new viewpoint for HLH therapy.

Renal cell carcinoma: treatment with recombinant interleukin-2 plus beta-interferon.

1990 ◽  
Vol 8 (3) ◽  
pp. 460-467 ◽  
Author(s):  
R L Krigel ◽  
K A Padavic-Shaller ◽  
A R Rudolph ◽  
M Konrad ◽  
E C Bradley ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Local Recurrence ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Nk Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Beta Interferon

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-beta) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-beta was administered three times weekly by intravenous (IV) bolus injection with 5 x 10(6) Cetus U/m2 of IL-2 and 6 x 10(6) U/m2 of IFN-beta to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Cordyceps sinensis as an Immunomodulatory Agent

1996 ◽  
Vol 24 (02) ◽  
pp. 111-125 ◽  
Author(s):  
Yuh-Chi Kuo ◽  
Wei-Jem Tsai ◽  
Ming-Shi Shiao ◽  
Chieh-Fu Chen ◽  
Ching-Yuang Lin
Keyword(s):  
Tumor Necrosis ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Cordyceps Sinensis ◽  
Fruiting Bodies ◽  
Nk Cell Activity ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the Iymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) production on human mono-nuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 =; 71.0 ± 3.0 and 21.7 ± 2.0 μg/ml, respectively), NK cell activity (IC50 =; 25.0 ± 2.5 and 12.9 ± 5.8 μg/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 =; 9.6 ± 2.3 and 5.5 ± 1.6 μg/ml, respectively). TNF-α production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 =; 2.7 ± 1.0 and 12.5 ± 3.8 μg/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.

scholarly journals Clinical Relevance of Diagnostic Criteria for Hemophagocytic Lymphohistiocytosis (HLH) and Survival Outcome of Adult HLH Patients: A Single-Center Prospective Cohort Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3718-3718
Author(s):  
Joon Young Hur ◽  
Kang Kook Lee ◽  
Jun Ho Jang ◽  
Kihyun Kim ◽  
Chul Won Jung ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Diagnostic Criteria ◽  
Prospective Cohort ◽  
Nk Cell ◽  
Cell Activity ◽  
Diagnostic Value ◽  
Adult Patients ◽  
Nk Cell Activity ◽  
Soluble Cd25 ◽  
Underlying Causes

Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated life-threatening condition in which activated macrophages phagocytize hematopoietic cells in various clinical situations from physiologic reactions to pathologic conditions such as malignancy. The diagnosis of HLH is currently done according to the HLH-2004 criteria which were mainly based on pediatric experiences even though underlying causes and clinical features of adult patients with HLH are different from pediatric patients. However, there is little information about the value of each item and its clinical relevance in the diagnosis of adult patients. Thus, we analyzed the diagnostic value of HLH-2004 criteria in adult patients who had symptoms or signs suspicious of hemophagocytosis. Methods We have conducted a prospective cohort study for adult HLH since January of 2017 (Prospective cohort for adult hemophagocytosis: NCT03117010). Adult patients older than 18 years having at least one of the following problems could be enrolled onto this prospective cohort: 1) Pathologically confirmed hemophagocytosis in bone marrow or lymph nodes; 2) Presence of at least 3 conditions among 8 items of HLH-2004 diagnostic criteria. After obtaining written informed consent, we performed laboratory tests for the diagnosis of HLH including natural killer (NK)-cell activity and soluble CD25 in blood. The primary objective of this study was to explore the feasibility and clinical usefulness of HLH-2004 criteria in adult patients, and secondary objective was to analyze underlying causes and outcomes of adult HLH. Results At the time of analysis, 44 patients were enrolled in the cohort, and their median age was 51.5 years (range, 19-85 years). Male (n=27) was more common than female (n=17). All patients had fever (body temperature ≥ 38.5°C) and splenomegaly was found in 29 patients (66%, Figure 1). Although cytopenia such as neutropenia and thrombocytopenia was commonly found, only 20 patients had bi-lineage cytopenia (45%). Hypofibrinogenemia and/or hypertriglyceridemia were also less common findings (n=18, 41%). Hemophagocytosis in bone marrow or lymph nodes was pathologically confirmed in 27 patients (61%). Elevated serum level of ferritin (≥ 500 mg/L) and soluble CD25 (≥ 2400 U/mL) were 42 (95%) and 35 patients (80%), respectively. Among 33 patients whose NK-cell activity was evaluated, 22 patients had low or absent NK-cell activity (67%). According to diagnostic criteria, 28 patients having at least five conditions were diagnosed with HLH, and the remaining patients including 7 patients with bone marrow hemophagocytosis could not be diagnosed. Among 28 patients with HLH, T/NK-cell (n=8) and B-cell lymphomas (n=7) were the most common underlying disorders (n=15, 54%). Infection including EBV (n=6) and rheumatologic disorders (n=3) accounted for non-malignancy associated HLH whereas the remaining four patients' cause was not identified. At the time of analysis, 14 patients died due to uncontrolled HLH or underlying disorders or infectious complications during treatment. The median overall survival of all patients was 13.9 months (95% CI: 10.9 - 16.9), and patients with HLH was not significantly different from patients without HLH (p=0.655). The survival outcome of patients with lymphoma was significantly worse than patients without it regardless of HLH diagnosis (p<0.001). Conclusions Fever and elevated level of serum ferritin were the most frequent condition in patients having suspicious symptoms of HLH. Low or absent NK-cell activity and increased level of soluble CD25 could have additional diagnostic value for timely diagnosis of adult HLH. Considering lymphoma is frequently associated with adult HLH, immediate evaluation for lymphoma should be done in adult patients suspicious of HLH. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Social Support, Psychological Distress, and Natural Killer Cell Activity in Ovarian Cancer

2005 ◽  
Vol 23 (28) ◽  
pp. 7105-7113 ◽  
Author(s):  
Susan K. Lutgendorf ◽  
Anil K. Sood ◽  
Barrie Anderson ◽  
Stephanie McGinn ◽  
Heena Maiseri ◽  
...  
Keyword(s):  
Social Support ◽  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Natural Killer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Nk Cytotoxicity

Purpose Psychosocial stress has been related to impaired immunity in cancer patients. However, the extent to which these relationships exist in immune cells in the tumor microenvironment in humans has not been explored. We examined relationships among distress, social support, and natural killer (NK) cell activity in ovarian cancer patients in peripheral-blood mononuclear cells (PBMC), ascitic fluid, and tumor-infiltrating lymphocytes (TIL). Patients and Methods Patients awaiting surgery for a pelvic mass suspected of being ovarian cancer completed psychological questionnaires and gave a presurgical sample of peripheral blood. Samples of tumor and ascites were taken during surgery, lymphocytes were then isolated, and NK cytotoxicity and percentage were determined. The final sample, which was confirmed by surgical diagnosis, included 42 patients with epithelial ovarian cancer and 23 patients with benign masses. Results Peripheral NK cell activity was significantly lower among ovarian cancer patients than in patients with benign masses. Among ovarian cancer patients, NK cytotoxicity in TIL was significantly lower than in PBMC or ascitic fluid. Social support was related to higher NK cytotoxicity in PBMC and TIL, adjusting for stage. Distress was related to lower NK cytotoxicity in TIL. A multivariate model indicated independent associations of both distress and social support with NK cell activity in TIL. Conclusion Psychosocial factors, such as social support and distress, are associated with changes in the cellular immune response, not only in peripheral blood, but also at the tumor level. These relationships were more robust in TIL. These findings support the presence of stress influences in the tumor microenvironment.

Comparison of Immunological and Endocrinological Markers Associated with Major Depression

2003 ◽  
Vol 31 (1) ◽  
pp. 36-41 ◽  
Author(s):  
H Jozuka ◽  
E Jozuka ◽  
S Takeuchi ◽  
O Nishikaze
Keyword(s):  
Major Depression ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Depression Scale ◽  
Serum Cortisol ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Nk Cell Activity ◽  
Self Rating

Natural-killer-(NK)-cell activity and blood levels of interleukin 2 (IL-2), dehydroepiandrosterone (DHEA), DHEA sulphate (DHEA-S) and cortisol were measured in 17 patients with major depression and 10 control subjects. Depression severity was evaluated using the Zung Self-rating Depression Scale. NK-cell activity and IL-2 levels were measured using a chromium-51 release test and an enzyme-linked immunosorbent assay, respectively. Radioimmunoassays were used to measure serum cortisol, DHEA and DHEA-S. As would be expected, patients with major depression had a higher score on the Zung Self-rating Depression Scale than healthy controls. Compared with controls, NK-cell activity and levels of cortisol and DHEA were reduced in patients with major depression, whereas IL-2 levels were increased. No difference was observed in DHEA-S levels between patients and controls. A reduction in NK-cell activity and DHEA levels, and an increase in IL-2 levels appear to be associated with major depression. Whether these changes are the cause or the consequence of the depression remains to be determined.

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