Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the correlations between the in vivo-in vitro induction of 2'-5' oligoadenylate synthetase (2-5A synthetase) by IFN-alpha in cells isolated from patients with low-grade nodular non-Hodgkin's lymphoma (NHL) and subsequent clinical responses of these patients to IFN-alpha therapy. Eleven patients were treated daily with 9 x 10(6) U of IFN-alpha 2a in a phase II trial. After an eight week treatment, four patients achieved complete remission, one a partial response, one a minor response, and five failed to respond. Basal levels of 2-5A synthetase in lymph node tumor B cells and peripheral blood mononuclear cells (PBMC) isolated before therapy differed from patient to patient and were significantly lower than in PBMC from healthy donors (P less than 0.03). In vivo single injections of 9 x 10(6) U IFN-alpha 2a induced the 2-5A synthetase in PBMC from all patients to various degrees without quantitative relation to the clinical responses. Injection of a tenfold lower dose resulted in effects of similar extent in most cases. In vitro, IFN-alpha 2a induced the 2-5A synthetase in lymph node tumor B cells isolated before therapy, and the degree of induction was significantly higher in patients who proved to respond to therapy than in patients who displayed no or minor responses (P less than 0.013). This indicates that, in nodular NHL, the 2-5A synthetase assay may have some predictive value for responsiveness to IFN-alpha therapy.
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PMID:In vivo and in vitro induction of 2'-5' oligoadenylate synthetase by interferon-alpha in nodular non-Hodgkin's lymphoma and correlations with the clinical response. 209 97

A severe and persistent pancytopenia occurred in a 42-year-old woman with a non-Hodgkin's lymphoma following a 10-day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU-E, BFU-E, CFU-GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E-rosette+, T gamma+, OKT8+ (suppressor/cytotoxic) T-and/or Leu 7+ natural killer (NK) lymphocytes and 50% were IgM Kappa, B1+, B-lymphocytes. In vitro erythroid culture studies were consistent with T-cell-mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10-day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T- and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.
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PMID:Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin. 241 Nov 29

Fifty per cent of untreated malignant lymphoma patients were shown to have profoundly reduced levels of peripheral blood lymphocyte-natural cell mediated cytotoxicity (PBL-NCMC) when tested against the leukaemic cell-line K562; assessment of NCMC in unfractionated blood from a large number of these patients showed a comparable reduction in activity. High levels of NCMC were observed in some patients with stage III/IV non-Hodgkin's lymphoma (NHL), while Hodgkin's disease (HD) patients over 40 yr of age had normal levels. In both NHL and HD patients there was no correlation between NCMC and absolute lymphocyte count or lymphoma histology. Human interferon was seen to boost NCMC in the majority of NHL patients, but most HD patients were nonresponders. Almost all patients tested had normal number of target binding lymphocytes, and most had numbers of HNK-1+ cells within the control range. However, on exposure to IFN, the number of target binding lymphocytes increased in over half of the patients tested, with some patients showing an increase in HNK-1+ cells, in the majority of cases without enhancement of NCMC.
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PMID:An assessment of natural cell-mediated cytotoxicity in patients with malignant lymphoma. 241 30

Natural killer (NK) activity and natural killer cytotoxic factors (NKCF) were found to be depressed in large granular lymphocytes (LGL) from the peripheral blood and lymph node lymphocytes (LNL) from untreated non-Hodgkin's lymphoma (NHL) patients. The LGL number was also reduced in NHL patients as compared to the normal subjects. The depression in all the activities mentioned above showed a correlation with the clinical status of the patients. Exogenous interferon-alpha (IFN-alpha) treatment of the effector cells could augment the NK activity to a comparable extent in normal as well as patient's LNL. The results indicate that the production of interferon may be affected in cases of NHL and therefore it would be worthwhile to test the tolerance and efficacy of IFN-alpha in these patients.
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PMID:Natural killer activity and NK cytotoxic factors in peripheral blood and lymph node cells from non-Hodgkin's lymphoma patients. 261 73

We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients.
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PMID:Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. 267 56

We treated 32 patients with Ph1-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon alpha-2b (IFN alpha-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM). IFN was given at daily doses of 1-4 x 10(6) IU. Twenty-seven patients (84%) responded, 17 (53%) achieved complete haematologic response after a median time of 12 weeks, and 10 (31%) partial haematologic response. Median platelet levels declined in complete haematologic response patients from 1,190 to 335 x 10(9)/l. Normalization of megakaryocyte (MK) levels was observed in 8/17 complete haematologic response patients treated for 9-12 months, with decreased bone marrow (BM) cellularity. Side effects requiring dose reduction or discontinuation of treatment occurred in 28% of cases with IFN doses of 2 or 4 x 10(6) IU. After 1 year of continuous IFN treatment, responses were maintained with conventional chemotherapy or low-dose IFN. This study demonstrates that IFN has definite therapeutic activity in CMD with excessive thrombocytosis. This biological agent, either alone or in combination with other antineoplastic treatment, may represent a new therapeutic approach for these disorders.
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PMID:Interferon alpha-2b as treatment for Philadelphia-negative chronic myeloproliferative disorders with excessive thrombocytosis. 275 63

Thirty-five patients with a diagnosis of non-Hodgkin's lymphoma of low histological grade were treated with 2 X 10(6)/m2 of human rDNA alpha 2 IFN-a2 by subcutaneous injection. Treatment was continued until progressive disease was documented or one year of therapy had been given. None of the patients had to stop treatment because of toxicity and no treatment delays or suspensions of therapy were necessary as a consequence of myelosuppression. Thirty four patients were evaluable and seventeen (50%) obtained an objective response (2 CR, 15 PR) with a median duration of eleven months. Sixteen patients were untreated prior to receiving interferon but were felt to need some form of therapy rather than be suitable for a watch policy. Eleven of these patients responded (69%) with 95% confidence limits lying between 41% and 89%. No other pretreatment factors appeared to affect the likelihood of response. Single agent IFN-alpha 2 has significant activity in the low grade non-Hodgkin's lymphomata and warrants further investigation in this disease.
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PMID:A phase II study of human rDNA alpha-2 interferon in patients with low grade non-Hodgkin's lymphoma. 375 60

A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.
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PMID:A multiple-dose phase I trial of recombinant leukocyte A interferon in cancer patients. 675 47

Interferon-alfa (IFN-alpha) has been evaluated in non-Hodgkin's lymphoma and multiple myeloma. The preclinical evidence that IFN-alpha has antitumor activity against non-Hodgkin's lymphoma includes genetic deficits in IFN-alpha production in patients with non-Hodgkin's lymphoma, direct antiproliferative effects of IFN-alpha in stem cell assays, and beneficial effects of combined IFN-alpha and chemotherapy in experimental models. Interferon-alfa was active in phase I and II studies of patients receiving prior chemotherapy for non-Hodgkin's lymphoma, particularly those with low- to intermediate-grade lymphoma. The results of randomized studies suggest that adding IFN-alpha to chemotherapy as either induction or maintenance therapy may improve the outcome in patients with previously untreated non-Hodgkin's lymphoma. Interferon-alfa also appears to have activity as a single agent in patients with multiple myeloma, and eventually may have a role as maintenance therapy in patients with multiple myeloma. Collectively, these studies reveal a trend toward using IFN-alpha in patients with smaller hematologic tumor burden instead of reserving it as a last-resort measure.
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PMID:Innovative treatment strategies for non-Hodgkin's lymphoma and multiple myeloma. 799 95


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