Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.
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PMID:Favorable response of early stage B CLL patients to treatment with IFN-alpha 2. 271 86

Immune function in patients with hairy cell leukemia (HCL) was examined serially during treatment with alternating monthly cycles of recombinant interferon alpha-2a and 2'-deoxycoformycin (dCF). At presentation, most patients had normal numbers of T lymphocytes and their cells had normal proliferative responses to mitogens [phytohemagglutinin (PHA) and concanavalin A (Con A)] and alloantigens. Patients had severe monocytopenia, decreased delayed-type hypersensitivity (DTH) reactions, and decreased peripheral blood natural killer (NK) activity. Treatment caused a profound decrease in all lymphocyte subpopulations. T cells were more affected than B cells or NK cells. Numbers of CD4+ and CD8+ lymphocytes decreased to levels less than 200 cells/microliters in all patients during treatment. This decrease in T cell number was associated with a marked decrease in proliferative responsiveness to PHA, Con A, and alloantigens. These abnormalities persisted throughout the 14 months of treatment and have continued for up to 6 months beyond discontinuation of treatment. NK cell activity increased during treatment, but cycled depending on the phase of treatment; highest activities were observed after interferon (IFN)-alpha and lower levels of activity were observed after dCF. DTH responses generally did not improve during therapy. Levels of IgM, IgG, IgA, and IgD did not change during treatment, but IgE levels rose in most patients. All immunosuppressive effects were attributable to dCF since patients receiving IFN-alpha 2a alone did not exhibit these same immunosuppressive effects, and patients receiving dCF alone after IFN failure exhibited similar abnormalities. Despite this severe immunosuppression from dCF, life-threatening opportunistic infections have not been observed in our patient population. Six patients developed localized Herpes zoster infection among 21 patients who had received dCF. Pending the results of long-term follow-up, we recommend that dCF be reserved for patients who have failed splenectomy and IFN therapy.
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PMID:Deoxycoformycin-induced immunosuppression in patients with hairy cell leukemia. 278 73

Cats exposed to the feline leukemia virus (FeLV) may mount an effective immune response and eliminate the virus, develop a non-viremic, latent infection or become persistently infected and shed the virus. Persistently infected cats commonly die of secondary opportunistic infections that result from FeLV-induced immunosuppression. The acquired immunosuppression is the most frequent and most devastating consequence of FeLV infection in the cat. Immunosuppression is targeted primarily to the cell-mediated immune system and has been attributed to the viral p15e envelope protein. The decreased IgG response and proliferative response to T cell mitogens is thought to be due to a defect in the helper cell function. As a result of T helper cell immunosuppression, infected cats may also have defective cytotoxic lymphocyte and activated macrophage functions which are regulated by their lymphokines. Research has shown that the virus causes a general suppression in the production of T cell-derived lymphokines, including gamma interferon and interleukin 2. A decrease in the function of polymorphonuclear leukocytes has also been reported and may contribute to deaths due to opportunistic infections in FeLV-positive cats. There are numerous parallels between the acquired immunodeficiency syndrome (AIDS) in man and the FeLV-induced immunodeficiency syndrome in cats. Frequent deaths due to opportunistic infections, lymphopenia, depressed cell-mediated immune responses to T cell-dependent antigens despite hypergammaglobulinemia and the presence of a long period of time between infection and the onset of clinical signs are just a few of the syndromes that are similar between the 2 retroviral diseases. A new strain of FeLV, FeLV-FAIDS has been associated with a naturally occurring immunosuppressive syndrome that is strikingly similar to AIDS in man. In addition, a T-lymphotropic retrovirus has recently been identified from cats with an immunodeficiency-like syndrome; this feline lentivirus disease is morphologically similar, but antigenically distinct from the human immunodeficiency virus, the cause of AIDS. Treatment for FeLV immunosuppression is primarily supportive. The development of a soluble tumor cell antigen vaccine has been shown to be efficacious in preventing FeLV infections.
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PMID:Clinical and immunologic aspects of FeLV-induced immunosuppression. 284 93

The immunological effects of long-term treatment with recombinant alpha-2 interferon (rIFN-alpha 2) were investigated in multiple sclerosis (MS) patients treated with 2 X 10(6) units of IFN or a placebo three times per week for one year. A mild lymphopenia was observed in IFN patients who also showed a decrease in the absolute number of total T cells in the blood (OKT3 binding cells); however, the percentage of cells reacting with OKT3, OKT4, and OKT8 antibodies did not change significantly during the study. The percentage of cells reacting with the Leu-7 antibody, which recognizes NK cells, was unchanged. During MS exacerbations, placebo patients showed a tendency for decreased levels of OKT3 and OKT8 cells. In contrast, IFN patients did not demonstrate a decrease in either OKT3 or OKT8 cells during disease attacks. Concanavalin A (ConA)-induced suppressor cell activity was depressed in both IFN and placebo-treated patients during attacks. Lymphoproliferative responses to phytohemagglutinin, pokeweed mitogen, and ConA were unchanged. These studies demonstrate that long-term treatment with rIFN-alpha 2 induces a generalized T-cell lymphopenia, but at this dose does not significantly affect the profiles of T-cell subsets and suppressor cell function in MS patients.
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PMID:The effects of long-term administration of recombinant alpha-2 interferon on lymphocyte subsets, proliferation, and suppressor cell function in multiple sclerosis. 294 93

Immunological competence plays an important role in response of patients to radiation therapy and dose of radiation required for tumor control depends also on the immunocompetence of the individual patient. Radiation therapy (even localized irradiation) can, however, cause lymphopenia and induce an immunodeficient state. This may facilitate growth of residual tumor cells or metastatic foci, this negating benefits of the therapy. A brief overview of damage to T and B lymphocytes as well as macrophages and natural killer (NK) cells by radiation therapy was presented. The restoration and potentiation of the immunological competence of the patients by biological response modifiers (BRM) such as OK432 (a bacterial preparation), recombinant interferon (rIFN-gamma) and recombinant interleukin-2 (rIL-2) with or without lymphokine activated killer (LAK) cells, were discussed.
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PMID:[Decrease in radio-sensitivity of the tumor by radiation-induced damage to immuno-related cells]. 295 6

Production of interferon (IFN)-gamma by peripheral blood leukocytes (PBL) was examined in cultures of unseparated fresh whole blood exposed to phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). The yield of IFN-gamma was measured by a newly developed immunoradiometric assay. Nine of 14 patients with acute pulmonary tuberculosis (TB) showed a depressed IFN-gamma response to Con A and/or PWM. Only four of these TB patients also showed a depressed IFN-gamma response to PHA. Stimulation of the patients' PBL cultures with PHA in the presence of exogenous interleukin 2 (IL 2) produced normal IFN-gamma yields in all but the most severely depressed patients. PBL cultures of TB patients with defective IFN-gamma production in response to mitogenic lectins also produced less IFN-gamma after stimulation with tuberculin PPD. Although some patients showed a moderate degree of lymphopenia, their OKT4/T8 lymphocyte ratios were mostly normal or close to normal, with the notable exception of one TB patient who has been diagnosed to have the acquired immune deficiency syndrome (AIDS).
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PMID:Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis. 308 65

The IF-producing capacity of human lymphocytes obtained by drainage of thoracic duct of surgical patients was studied. The lymph cells incubated with the appropriate inducer produced interferon of alpha and gamma types. The level of IF production, particularly of the gamma type, was negatively influenced by the storage of lymph at +4 degrees C and recovery of the cells in ficoll-hypaque gradient. The time course of IF production was found on the whole to be similar to that in the peripheral blood lymphocytes. The level of alpha-IF synthesis was higher for blood cells, and that of gamma-IF for lymph cells. The synthesizing capacity of the thoracic duct lymphocytes decreased in the acute stage of the disease and increased during convalescence which was especially typical of gamma-IF production.
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PMID:[Production of alpha- and gamma-interferons by human central lymph cells in different pathological states]. 310 35

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.
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PMID:Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma. 348 11

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells generated from autologous lymphocytes has produced significant tumor regressions in patients with advanced cancer. In the current study, we reviewed the hematologic effects associated with this therapy in our initial 42 patients. Eighty-eight percent of the treated patients developed anemia that required greater than or equal to 4 units of red cell transfusions, and 43% received at least 8 units. Only a blood loss of 2 to 3 units could be attributed to repeated phlebotomy, cytophereses, and hemodilution. IL-2 administration also resulted in thrombocytopenia as well as lymphopenia and eosinophilia. Forty-three percent of patients developed platelet counts of less than or equal to 50,000/microL, and 36% of the total group required platelet transfusions. Mild neutropenia and a rebound lymphocytosis followed discontinuation of IL-2 treatment. To explore the possible mechanisms for these hematologic effects, standard hematopoietic colony assays were conducted on serial blood samples from five patients. IL-2 produced a significant decline in circulating erythroid (BFU-E) and granulocytic/macrophage (CFU-C) progenitors, which rebounded after the discontinuation of IL-2 therapy. Infusion of IL-2 also resulted in measurable serum levels of gamma-interferon. Some of the hematologic effects of immunotherapy with LAK cells and IL-2 may be the result of IL-2-mediated suppression of hematopoiesis.
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PMID:Hematologic effects of immunotherapy with lymphokine-activated killer cells and recombinant interleukin-2 in cancer patients. 349 2

Studies were initiated to assess the response of patients with disseminated melanoma to recombinant alpha interferon (rIFN-alpha A) and to monitor effects of rIFN-alpha A on several tests of immune function. Twenty patients were treated with rIFN-alpha A given by i.m. injection in escalating doses from 15 to 50 X 10(6) um-2. The responses of two patients were considered unevaluable. Of the remainder there was complete remission of tumour in two and stable disease in two. Subsequent progression of tumour in one of the latter patients coincided with development of antibodies to IFN. Side effects (usually fatigue) were dose rate limiting in 11 patients. Laboratory tests on samples taken 6 hours after rIFN-alpha A indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity particularly against K562 target cells. Longer term changes measured in samples taken 2 days after the previous rIFN-alpha A injections consisted of neutropenia and an increase in the T4/T8 ratio due mainly to a relative increase in OKT4 positive T cells compared to OKT8 positive T cells. NK activity against the K562 target cell increased in most patients during the first week of treatment and then returned to below or near pretreatment levels thereafter against the K562 target cell. This contrasted with NK activity against the melanoma target cell which showed a more gradual increase over the duration of the treatment in 6 patients. The latter correlated with an increase in mitogen stimulated IL 2 production from their blood lymphocytes and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. These results confirm the activity of rIFN-alpha A against melanoma in certain patients. They suggest that further studies are needed to select patients who may respond to rIFN-alpha A and to optimize treatment regimens. Tests of IL 2 production and LAK activity may assisted in achieving these objectives.
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PMID:Effects of recombinant leukocyte interferon (rIFN-alpha A) on tumour growth and immune responses in patients with metastatic melanoma. 387 53


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