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)

23 newly diagnosed patients affected by cutaneous T-cell lymphoma were treated with sub-cutaneous interferon alpha-2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74-yr-old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow-up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha-2a is a very effective agent in therapy of untreated cutaneous T-cell lymphoma with an overall response rate of 74%.
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PMID:Interferon alpha-2a in cutaneous T-cell lymphoma. 227 44

Thirteen patients with metastatic malignant melanoma received interferon alpha-2a (Roferon-A) and vinblastine. The interferon dosage was increased from 3 x 10(6) IU to 9 x 10(6) IU daily in 10 weeks and thereafter 9 x 10(6) IU was administered three times weekly intramuscularly. Vinblastine (0.075-0.15 mg/kg) was given every third week intravenously. One of the ten evaluable patients had partial remission (PR) (11%) for 10 months. The diseases was stabilized (NC) in three patients (30%) for 3, 6 and 9 months. Progression (PD) occurred in six patients. The treatment time varied from 5 weeks to 44 weeks. The median survival time from the beginning of this combination treatment was 5 months. The most common side-effects were fever, fatigue, loss of taste, weight loss and neutropenia. The mitogen response to phytohemagglutinin and purified protein derivative of tuberculin decreased in all patients. The response to concanavalin A decreased less and began to increase again in the patients with PR and NC. The natural killer cell activity in PD patients decreased more than in the patients with PR and NC. The ratio of T4/T8-positive cells was restored in PR + NC patients but rose in PD patients indicating a difference in the immunomodulatory effect of the combination or of the advanced disease itself on T-cell function in PD patients. This combination of daily interferon and vinblastine did not prove to be effective in melanoma. The depression of immunological functions, which was more marked in patients with PD, might indicate that vinblastine in this combination counteracts the immunostimulatory effect of interferon.
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PMID:Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions. 278 56

In two phase I-II trials, 33 patients were given recombinant interferon alpha-2 daily at dosages of 3, 10, 30, 50, or 100 MU/d for up to 4 weeks by intramuscular or intravenous routes. Dose-limiting toxicities, including neutropenia, elevated hepatocellular enzyme levels, fatigue, and disturbed mentation, correlated with differing serum pharmacokinetics of interferon in the two trials. In the intramuscular study, dose-limiting toxicity occurred at all dosages greater than 10 MU/d, at a median of 6 to 9 days of treatment. In the intravenous dose-study, limiting toxicity was seen only at dosages of 100 MU/d, at a median of day 8. Twenty-three patients had metastatic melanoma and 4 had objective partial or complete responses at dosages of 10 to 50 MU/d in the first month. Two patients with complete responses are free of tumor after 2.5 years of follow-up. A fifth patient had delayed complete regression, requiring 1 year to achieve maximum response, but remains free of disease at 26 months since entry to the trial. Interferon had antitumor activity against melanoma by both routes tested, at dosages of 10 to 50 MU/d.
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PMID:Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. 400 87

Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses were delivered every week. Moreover those pts with > or = 10% blasts in the bone marrow were additionally treated with low dose cytosine arabinoside (LDARAc) (20 mg standard dose, subcutaneously, twice a day for seven days every four weeks). Sixteen pts were finally assessable for response. Seven pts (44%) were classified as good responders, 5 (31%) had a PR; the overall response rate (GR+PR) was 75%. Two pts (12.5%) showed stable disease and the 2 remaining (12.5%) had progressive disease. Six pts with an initial moderate anemia never required supportive care before and during the therapy; in contrast to 10 pts who were transfusion-dependent. After six months of therapy 2 pts decreased their transfusional needs by 50% (1 of them did not receive any transfusion over the following six months of therapy); 2 pts needed no packed red cell infusions and 1 pt decreased his transfusional support by 75%. Five pts kept an unchanged supportive care load. The overall median survival was 12.5 months. Therapy was generally well tolerated with acceptable compliance; the most frequently recorded side effects were neutropenia and thrombocytopenia grade 2-3 among the group receiving LDARAc. However no life-threatening infectious episodes or bleeding were observed. TP, rIFN alpha 2a and LDARAc can be safely administered on an outpatient basis to MDS pts and appears to have significant activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant interferon alpha 2a, thymopentin and low doses of cytosine arabinoside for the treatment of myelodysplastic syndromes: a pilot study. 771 40

This study reports the characterization of a spontaneous lymphoblastoid cell line (LCL) raised from the peripheral blood of a patient with Kostmann's congenital neutropenia. The LCL was composed of EBV-infected polyclonal B cells and displayed surface markers and pattern of growth in vitro typical of normal LCLs. The supernatant of the LCL contained a colony inhibiting activity (CIA) that decreased the cloning efficiency of normal committed haemopoietic progenitors and was identified as immunoreactive transforming growth factor beta 1 (TGF-beta 1) by neutralization experiments with a specific antiserum. Control studies with a panel of LCLs spontaneously derived from the peripheral blood of patients seropositive for Epstein-Barr virus (EBV) infections showed that 5/30 LCLs produced a CIA. This CIA was not identifiable as TGF-beta 1 but rather was due to the combined effects of tumour necrosis factor alpha (TNF alpha), tumour necrosis factor beta (TNF beta) and interferon alpha (IFN alpha), that were present in the LCL supernatants. The hypothesis that the B cells latently infected by EBV in vivo and possibly expanded as a consequence of the infection may have contributed to the inhibition of the patient granulopoiesis by releasing TGF-beta 1 will be discussed.
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PMID:Transforming growth factor beta-1 (TGF-beta 1) released by an Epstein-Barr virus (EBV) positive spontaneous lymphoblastoid cell line from a patient with Kostmann's congenital neutropenia inhibits the growth of normal committed haemopoietic progenitors in vitro. 791 30

Forty-three consecutive patients with advanced melanoma not previously treated with cytotoxic drugs (22 of them had already received adjuvant recombinant interferon alpha 2a (rIFN alpha 2a)) were given a combination of intravenous (i.v.) fotemustine (FM), 100 mg/m2 on day 1, and dacarbazine (DTIC), 250 mg/m2 i.v. on days 2-5, every 3 weeks. rIFN alpha 2a was administered at the dosage of 3 MIU subcutaneously 3 times a week until progression. Four complete and 13 partial responses were registered, for an overall response rate of 40% (95% CI, 25-56%). Activity of this regimen was similar in patients with mainly visceral (10/22, 45%) or soft tissue (6/13, 46%) involvement. The median duration of responses was 24 weeks. Median survival time was 40 weeks, with a 13% 2 year survival rate. Neutropenia and thrombocytopenia affected 67% and 51% of patients, but were of WHO grade 4 in only 2% and 5% of them, respectively. Side-effects attributable to rIFN alpha 2a were mild and manageable. In conclusion, the combination of FM + DTIC and rIFN alpha 2a seemed well tolerated and relatively active in patients with advanced melanoma. However, the role of rIFN alpha 2a in affecting the long-term outcome of patients is still questionable.
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PMID:Fotemustine and dacarbazine plus recombinant interferon alpha 2a in thetreatment of advanced melanoma. 930 63

Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and interferon alpha (IFNalpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNalpha-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times a day) and IFNalpha-2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received.
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PMID:The combination of zidovudine and interferon alpha-2B in the treatment of adult T-cell leukemia/lymphoma. 1142 50

To determine the clinical characteristics and outcome of patients with chronic hepatitis C virus (HCV) infection presenting severe autoimmune cytopenia unrelated to interferon alpha therapy, we analyzed characteristics and outcomes of 35 patients with HCV (16 from our departments and 19 from the literature). We considered active autoimmune hemolytic anemia (AHA) as a decrease of at least 2 g/dL in hemoglobin levels, an increase of at least 0.6 mg/dL in the serum unconjugated bilirubin level, a reticulocyte count >5%, and a positive direct Coombs test. Severe neutropenia was defined as a neutrophil count <0.5 x 10(9)/L, and severe thrombocytopenia as a platelet count <30 x 10(9)/L. We identified the following cytopenias: AHA (17 cases), severe thrombocytopenia (16 cases), aplastic anemia (2 cases), severe neutropenia (1 case), refractory sideroblastic anemia (1 case), and pure red cell aplasia (1 case). Three patients simultaneously presented 2 types of severe cytopenias. Twenty-seven patients (77%) were female and 8 (23%) male, with a mean age at diagnosis of cytopenia of 51.7 years (range, 18-84 yr). Immunologic markers were detected in 19 (68%) of 28 patients, the most frequent being hypocomplementemia in 16 (57%), cryoglobulins in 15 (54%), antinuclear antibodies in 12 (43%), and rheumatoid factor in 5 (18%). Other associated processes were autoimmune diseases in 14 (50%) of 28 and human immunodeficiency virus (HIV) coinfection in 3 (9%) of 32. We found clinical and immunologic differences between HCV patients with AHA and those with severe thrombocytopenia. Patients with HCV-related AHA showed a higher prevalence of associated autoimmune diseases (71%), cryoglobulins (67%), and cirrhosis (59%). All had a good response to corticosteroids, but a poor prognosis (47% mortality). In contrast, patients with HCV-related severe thrombocytopenia had a lower prevalence of associated autoimmune diseases (11%), a poorer response to corticosteroids (55%), and lower mortality (6%), with HIV/HBV coinfections in some patients. The 35 cases presented demonstrate that different types of immune-mediated cytopenias may be severe and clinically significant in patients with HCV infection. Hemolytic anemia and severe thrombocytopenia were the most frequent cytopenias observed. Most patients responded well to corticosteroids, although a higher rate of mortality was observed in those with liver cirrhosis.
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PMID:Severe autoimmune cytopenias in treatment-naive hepatitis C virus infection: clinical description of 35 cases. 1264 Jan 85

Our aim was to determine the efficacy of ifosfamide, mesna, and interferon alpha combination therapy in malignant mesothelioma (MM) patients. Fourty-two patients (39 evaluable) with histologically proven MM were enrolled into this study from January 1999 to October 2002. The drug schedule consisted of a combination of ifosfamide, 3000 mg/m2 1-3 d intravenous infusion (iv), the uroprotective agent mesna, 3000 mg/m2 1-3 d iv every 3 wk, and interferon alpha2a, 4.5 MU subcutaneously (sc) 3 d/wk for 6 mo as first-line chemotherapy. Overall, 140 cycles were administered to the 39 patients (median, 3.5 cycles; range, 1 to 6 cycles). Among the 39 patients, 8 partial remissions (PR) (21%) were observed. Thirteen patients (33%) had stable disease for at least 8 wk and 18 (46%) had progressive disease. Overall survival (OAS) and progression free survival (PFS) for all patients were 10.0 +/- 2.9 mo (95%CI 4.3-15.7) and 5.0 +/- 1.9 mo (95%CI 1.38-8.62), respectively. One and two year survival rates were calculated as 39% and 5%, respectively. All of the PR patients had the epithelial type of MM. Their survival time was 21.0 +/- 5.7 mo (95% CI 9.9-32.1) and significantly longer than that of nonresponders (p=0.0061). The toxicity of the drug combination was mild and well tolerated. There were no treatment-related deaths. Grade 3-4 neutropenia and febrile neutropenia were seen in 10 patients (26%) and 3 patients (8%), respectively. Chemotherapy was stopped in three patients because of renal function deficiency. One of these patients who had peritoneal MM required hemodialysis. In conclusion, this combination therapy showed encouraging antitumor activity with modest toxicity.
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PMID:Ifosfamide, mesna, and interferon-alpha2A combination chemoimmunotherapy in malignant mesothelioma: results of a single center in central anatolia. 1557 20

We have reported that increasing the length of infusion from 5 min to 1 h appeared to substantially reduce the toxicity associated with fluorouracil (5-FU) modulated by leucovorin (LV) and interferon alpha-2a (IFN-alpha). This phase II study assessed the antitumor efficacy of this regimen. Patients (n=38) with colorectal cancer received IFN-alpha 5 MU/m(2) SC on days 1-6; on days 2-6, LV 200 mg/m(2) IV was given with 5-FU at initial doses of 370-425 mg/m(2)/h. The regimen was well-tolerated with no grade 4 toxicity. At 425 mg/m(2) 5-FU, grade 3 toxicities included diarrhea (8.6%), anorexia, fever and fatigue (5.7% each), neutropenia and nausea/vomiting (2.9% each). Individuals tolerated 5-FU doses up to 644 mg/m(2). Objective responses occurred in 27% of 37 patients; median time to progression and survival were 6.1 and 12.9 months. Only 1 of 25 informative tumor samples had high-frequency microsatellite instability (MSI), while 7 of 23 assessable patients (30%) with MSI-negative tumors had an objective response. With 425 mg/m(2), the average 5-FU Cp and AUC(0-1 h) were 37.4 microM and 1161 microM/h. Some 6 patients had extended sampling, and the half-lives of 5-FU and FBAL (apparent) were 8.6 and 100.0 min, respectively. A 1-h infusion of 5-FU is well tolerated; individual dose escalation of 5-FU allows each patient to receive the maximum tolerable dose.
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PMID:A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon alpha-2a in adenocarcinoma of the large bowel. 1587 Sep 35


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