Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and secondary effects of an induction dose of interferon-alpha2b (IFN-alpha2b) with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C infection were compared. A prospective study was undertaken between March 1998 and November 2001 in which 84 Spanish hospitals took part. Six hundred and fourteen naive patients (age range 18-65 years) diagnosed with chronic hepatitis C virus (HCV) infection and without cirrhosis or co-infection by other viruses, were included. Patients were divided into two groups. Group A (n = 304) received induction treatment with a daily dose of 5 MU of IFN-alpha2b for 4 weeks, followed by 5 MU three times a week with ribavirin (1000-1200 mg/day, according to weight) until completing 1 year of treatment. Group B (n = 310) received the standard dose of IFN-alpha2b of 3 MU three times per week for 48 weeks together with ribavirin (1000-1200 mg/day, according to weight). Both groups were completely comparable according to age, gender, body weight, transaminase levels, genotype, viral load and hepatic inflammatory activity (Knodell Index). No control group was included for ethical reasons. Pegylated interferon was not available at the time of the study. Serum baseline samples were collected for the determination of genotype. Samples were also collected at baseline, weeks 4, 12, 24, 48 and 72, in order to detect and quantify HCV-RNA. The efficacy of treatment was evaluated by means of sustained viral response (SVR) characterized by persistent negativity of HCV-RNA at the end of the follow-up period. At week 4, the response to treatment was greater in group A (49.6%) compared with group B (34.5%) (P = 0.0002), and was maintained until week 12 (64.1% compared with 55.8% respectively) (P = 0.03). These differences disappeared at week 24, when group A (69%) was compared with group B (65%) (NS). At week 48, the response rate for group A was 50.6% compared with group B 47.4% (NS), and at week 72, the SVR in group A was 46% compared with 40.3% for group B (NS). The global SVR was 43.1%. On analysing the response to treatment according to genotype and viral load, we found that the induction treatment was slightly superior in patients with genotype 1 and an elevated viral load (>2 x 10(6) copies/ml). They achieved a SVR in group A of 39.1% compared with 25.5% in group B (P < 0.05). However, this slight improvement obtained in group A, was achieved at the expense of a greater percentage of dropouts compared with group B (6.4% vs 2.2%, P < 0.01); a greater rate of side effects (58.5 vs 36.7%, P < 0.05) and also a greater percentage of neutropenia (3.1% vs 0.9%, P < 0.05). The induction treatment presented a better initial response, but this was not maintained at the end of treatment, and did not improve the results obtained with the standard treatment. Although the patients with genotype 1 and elevated viral load had a better response with the induction treatment, this was accompanied by a greater percentage of dropouts and secondary effects. It would be interesting to repeat this type of study in the future, using pegylated interferon.
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PMID:Comparative study of the efficacy of an induction dose of interferon-alpha2b with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C. 1463 77

To characterize the cellular components responsible for the impaired granulopoiesis in chronic idiopathic neutropenia (CIN), we investigated the origin of the proapoptotic cytokine producing cells in the bone marrow (BM) microenvironment of CIN patients. We found that the interferon gamma (IFN gamma) and/or Fas-ligand expressing cells in patient BM mononuclear cells and long-term BM culture stroma cells were the CD3(+) T-lymphocytes but not the CD14(+) monocytes/macrophages. The percentage of activated T-lymphocytes was increased in patients' BM as indicated by the proportions of human leucocyte antigen (HLA)-DR(+), CD25(+), CD38(+), CD69(+) and Fas(+) cells within the CD3(+) fraction. Intracellular IFN gamma expression was higher in the BM than peripheral blood of the patients and was associated with increased BM T-lymphocyte numbers. In crossover experiments, patient CD3(+) T-lymphocytes conferred autologous and allogeneic haemopoietic progenitor cell colony inhibition. Patients' T-cell receptor repertoire and polymerase chain reaction analysis did not reveal any clonal T-lymphocyte expansion, suggesting the absence of a direct, antigen-driven recognition of CD34(+) myeloid progenitor cells by patient T-lymphocytes. We conclude that CIN patients have increased number of activated T-lymphocytes in the BM, probably in the setting of a localized polyclonal immune reaction and that these cells confer an inhibitory effect on myelopoiesis through myelosuppressive cytokines including Fas-ligand and IFN gamma.
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PMID:Activated T-lymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia. 1575 93

Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
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PMID:Treatment of chronic hepatitis B infection using interferon. 1610 70

Sustained virologic response rates are significantly higher in patients who have relapsed after a previous course of therapy compared with patients who did not respond. A meta-analysis of combination therapy in patients who failed IFN monotherapy reported SVR rates of 52% in relapsers to prior therapy and 16% in nonresponders. Similarly, relapsers after combination standard IFN and RBV therapy have higher SVR rates than combination of therapy nonresponders when treated with pegylated interferon and ribavirin. For this reason, patients who relapse after a previous course of therapy should be considered potential candidates for retreatment. Factors that have been associated with SVR in these patients include genotype non-I, low viral loads, and lesser degrees of fibrosis. The course of treatment in all patients who have relapsed after prior therapy should be reviewed to identify possible reasons for failure to achieve an SVR. In particular, optimal dosing of PEG IFN and RBV and the occurrence and timing of treatment dose reductions during prior therapy should be reviewed. The reasons for dose reduction should be addressed before initiating another course of therapy in an effort to optimize the chance for a SVR. Patients who had dose reduction for depression, anemia, or neutropenia, should be considered for antidepressants, erythropoietin, or, if neutropenia is severe, granulocyte colony stimulating factor therapy, respectively, during retreatment. Prolongation of therapy beyond 48 weeks in patients with relapse after a standard course of PEG IFN and RBV may offer a chance of SVR. Novel agents currently in development, including protease and polymerase inhibitors, may prove to be therapeutic options for these patients in the future.
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PMID:Treatment of relapsers after combination therapy for chronic hepatitis C. 1532 41

An IFL regimen combining irinotecan, a bolus administration of 5-fluorouracil (5-FU) and leucovorin (LV) was associated with a significantly better response rate, progression-free survival and median overall survival, compared to 5-FU/LV against metastatic colorectal cancer. Despite a favorable initial report, randomized trials have suggested that triple therapy may be more toxic (severe neutropenia, diarrhea), leading to unacceptably high rates of early treatment-related mortality. On the other hand,a survival benefit for the oxaliplatin-containing regimen (FOLFOX 4) compared to bolus IFL, has been shown from INT trial 9741, and a European trial (V 308) suggests similar efficacy for combinations of irinotecan or oxaliplatin with short-term infusional 5-FU/LV (FOLFIRI or FOLFOX 6). Overall, FOLFIRI or FOLFOX regimen is now a standard option for first-line treatment of metastatic CRC.
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PMID:[IFL]. 1683 78

Interferon-alpha (IFN-Alpha) + cisplatin (CDDP) + 5-FU therapy was given to 10 patients with gemcitabine (GEM)-refractory unresectable or recurrent pancreatic cancer. CDDP (35 mg/m(2)) was administered intravenously on the first day, IFN-Alpha (5x10(6)IU) subcutaneously on day 2,4 and 6 of each week, and 5-FU (175 mg/m(2)/day) continuously infused every day for 4 weeks. The 10 patients consisted of 8 men and 2 women with a mean age of 56.2 years. As the main site of progression, 5 patients had liver metastases, 1 had lung metastases, 2 had peritoneal dissemination, and 2 had local recurrence. The objective response rate was 30%, including 1 complete response. Grade 3 anorexia, neutropenia and thrombocytopenia occurred in 60%, 40% and 40%, respectively. IFN-Alpha + CDDP + 5-FU therapy is an effective treatment for GEM-refractory pancreatic cancer, but with moderate toxicity.
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PMID:[Interferon-alpha+cisplatin+5-FU therapy for gemcitabine-refractory unresectable and recurrent pancreatic cancer]. 1683 83

Liver disease caused by hepatitis C virus infection is associated to significant morbidity and mortality among patient with end stage renal disease on maintenance hemodialysis (HD). Therapy in these patients consists of Interferon, preferably pegylated Interferon (pIFN), thus Ribavirin (RBV) is not recommended for patients with impaired renal function, outside its use in controlled trials. We report a case of 35 years young woman on HD treatment, renal transplantation candidate with chronic hepatitis C virus infection, HCV RNA positive (by PCR), genotype 3a, moderate viral load, light increase of aminotransferases. Pegylated Interferon alfa-2a (135 mcg/weekly/SC) was initiated. She achieved HVC RNA negative within 12 weeks, following with pINF as monotherapy to complete 24 weeks (6 months). Sustained virologic response persisted to 24 and 48 weeks. Most important side effects were light detriment of anemia, moderate neutropenia and thombocytopenia, transitory elevation of transaminases and "flu-like" syndrome. Adverse events were well tolerated with total compliance with pIFN dose, no requiring reduce or stop the treatment. These findings confirm that hemodialysis patients with chronic hepatitis C respond well to pegylated IFN monotherapy and a long-term sustained virologic response is achieved, appears to be better tolerated with less side effects, so combination therapy with pINF plus ribavirin is not necessary in all cases.
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PMID:[Good virological response to pegylated interferon alfa monotherapy of chronic hepatitis C infection in hemodialysis patient]. 1740 84

The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C; to compare the efficacy of two strategies of management of neutropenia--with Interferon dose modification and with Neupogen administration; to compare the effectiveness rate of sustained viral response (SVR) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim. (Neupogen). Study enrolled 47 patients with chronic active hepatitis C, aged 23-64. (38 male and 9 female). All patients had HCV genotype 1b. Significant neurtopenia (ANC<750 mm3) and severe neurtopenia (ANC<500 mm3) developed in 41 of 47 patients (87%). 41 patients with neurtopenia were randomized into two groups. The first group--22 patients who received granulocyte colony-stimulating factor (G-CSF, or filgrastim) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment. In all 22 patients of the first group neutropenia was normalized without reduction and/or inhibit of Pegylated interferon. Neupogen was well tolerated and in all 22 patients the improvement of quality of life (QOL) was observed. It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1. In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose (without reduction). Neupogen has the potential to improve adherence rates, which may in turn improve SVR.
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PMID:IFN/RBV treatment induced neutropenia and its correction with neupogen in patients with hepatitis C. 1766 Jun 2

Many patients with chronic hepatitis C (HCV) infection undergoing treatment with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin develop neutropenia requiring dose reduction or granulocyte colony-stimulating factor (G-CSF) supplement. We analysed the database of patients who completed treatment for chronic HCV infection between 2003 and 2006. Patients with absolute neutrophil counts below 1000 cells/microL were initiated on G-CSF (G-CSF group) while a matching group of patients who received anti-HCV treatment without developing neutropenia were used as a control group (non-G-CSF group). Patients on the G-CSF arm were divided into two subgroups based on the timing of G-CSF administration relative to PEG-IFN-alpha administration. Of the 163 patients with HCV infection, 30 patients received G-CSF, most of who were maintained on 300 microg of G-CSF once a week. Administration of G-CSF 2 days before or after each dose of PEG-IFN-alpha did not make a significant difference in the neutrophil counts. In the G-CSF arm, 23 of 30 patients (77%) had undetectable end-of-treatment viral response which was comparable with 27 of 30 in the control group (90%; P = 0.17). There was no statistically significant difference in the sustained viral response between the two groups (61%vs 76%, P = 0.18). In most patients PEG-IFN-alpha induced neutropenia improved with a once-a-week dose of G-CSF with a comparable virological outcome. Timing of G-CSF administration did not make any significant impact on the patient's neutrophil counts but was better tolerated when given 2 days apart from PEG-IFN-alpha.
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PMID:Granulocyte colony-stimulating factor dosing in pegylated interferon alpha-induced neutropenia and its impact on outcome of anti-HCV therapy. 1792 14

Pegylated (PEG)-IFN-alpha-2a is a modified form of recombinant human IFN-alpha-2a with sustained absorption and prolonged half-life. Our aim was to evaluate its safety profile in adjuvant treatment of high-risk melanoma patients in a single centre setting and to compare this safety profile with data obtained from the literature for a) low dose IFN-alpha and b) high dose IFN. Eighteen consecutive melanoma patients (AJCC 2002 stages IIa-IIIc) were retrospectively analyzed for toxicities associated with adjuvant PEG-IFN-alpha-2a (180 microg/week s.c.). The most frequently reported adverse events were constitutional side effects (78%), myelosuppression (83%) and hepatotoxicity (78%). The proportion of patients receiving PEG-IFN-alpha-2a and suffering from myelosuppression and liver toxicity was significantly higher than for patients reported in the literature undergoing low-dose IFN-alpha treatment (P = 0.008, P = 0.001 respectively), while fatigue and depression were seen less frequently with PEG-IFN-alpha-2a. By contrast, compared to patients treated with high-dose IFN-alpha, PEG-IFN-alpha-2a treated patients less frequently experienced fatigue (P < 0.001), neutropenia (P < 0.068) and neuropsychiatric (statistically not significant) adverse events. In conclusion, subcutaneously delivered PEG-IFN-alpha-2a is well tolerated in a once-weekly dose of 180 mug by most patients with high risk malignant melanoma. The frequency of side effects is increased compared to low dose, but reduced compared to high dose standard IFN-alpha. Due to its pharmacokinetic properties, pegylated IFN-alpha has, as in the treatment of hepatitis C, potential for increased efficacy in adjuvant therapy of melanoma.
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PMID:Safety of pegylated interferon-alpha-2a in adjuvant therapy of intermediate and high-risk melanomas. 1808 86


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