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)

Alpha-2 interferon, produced in Escherichia coli using recombinant DNA techniques, was administered to 17 children with refractory acute lymphoblastic leukemia (ALL) in relapse, two children with TdT-positive, Philadelphia chromosome-positive chronic myelocytic leukemia (CML) in blast crisis, and one child with B cell (SIg+) non-Hodgkin's lymphoma (NHL) in a second extramedullary relapse. An initial 2-week intravenous (IV) phase of interferon was followed by a 3-month subcutaneous (SC) maintenance phase if patients had an objective response or disease stabilization without significant bleeding or infectious complications. When interferon dosages were escalated from 3 to 100 X 10(6) U/m2 in the first phase of therapy, there was rapid progression of disease in the first four patients treated, prompting a modification of the treatment plan. The last 16 patients enrolled received fixed dosages of interferon (ie, 10, 20, 30, and 50 X 10(6) U/m2 administered to four subjects each). One child with T cell ALL had an 11-month complete remission; the patient with lymphoma had a dramatic but brief response; three others (one CML and two ALL) showed disease stabilization for 3 to 6 months with a definite oncolytic effect in two of the three patients. The remaining 15 patients had progressive disease within 2 months and were removed from the study. Acute toxicity included a flu-like syndrome in all patients, increased serum transaminase levels in five, seizures in three (two cases temporally related to fever and one to a thrombocytopenic subarachnoid hemorrhage), and prolonged activated partial thromboplastin times in seven. This phase I-II trial of recombinant alpha-2 interferon demonstrated definite activity without dose-limiting toxicity.
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PMID:Phase I-II study of recombinant alpha-2 interferon against advanced leukemia and lymphoma in children. 345 76

Maximally tolerated doses of interferon alfa-2a, 50 X 10(6) U/m2 administered intramuscularly (IM) 3 times weekly, were given to 20 patients with advanced stages of cutaneous T-cell lymphoma (CTCL) to determine the efficacy and toxicity of this therapy. All patients were heavily pretreated and had failed standard therapies. Objective remissions were noted in 45% of the patients, including two patients who achieved complete remissions and seven patients who had partial remissions. The median duration of response was 5.5 months, with responses lasting a minimum of 3 months and a maximum of more than 3 years. Responses in excess of 2 years occurred in three of the nine responding patients. These results were achieved with moderate toxicities. The dose-limiting toxicity was a flu-like syndrome consisting of malaise, anorexia, weight loss, and falling performance status. Toxicity was observed in all patients but was always alleviated by dose reduction. Patients with indolent B-cell non-Hodgkin's lymphoma who received the same therapy had a similar objective response rate (54%) and showed the same toxicities. These trials were followed by an ongoing trial using the same dose of interferon in a different schedule given for 12 weeks followed by a dose escalation to 100 X 10(6) U/m2. Three partial responses were observed in the first 13 patients on this trial treatment. Other studies examining lower dose interferon compared to the 50 X 10(6) U/m2 are in progress. This study establishes interferon alfa-2a as a treatment of choice for patients with advanced cutaneous T-cell lymphomas refractory to chemotherapy and other standard therapies. Trials combining interferon with other standard treatments and the use of interferon in earlier stages of disease are needed.
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PMID:The role of recombinant interferon alfa-2a in the therapy of cutaneous T-cell lymphomas. 348 12

In 1981, the National Cancer Institute undertook Phase II trials of interferon alfa-2a in patients with non-Hodgkin's lymphoma (including cutaneous T-cell lymphoma [CTCL]) and chronic lymphocytic leukemia (CLL). A dose of 50 X 10(6) U/m2, three times per week, was used initially, then adjusted downward as dictated by toxic effects. A 54% response rate was achieved among 24 patients with low-grade non-Hodgkin's lymphomas, and the median duration of response was 8 months. Less encouraging results emerged from studies in patients with intermediate- or high-grade disease. Responses were noted in only two of six patients in the former group, and only one of seven in the latter group. Results have likewise been disappointing in patients with CLL. Of 18 individuals treated, only two exhibited brief, partial responses. In CTCL, on the other hand, alpha interferon may be the most effective single agent. Among 20 patients with advanced disease who had failed previous therapies, 45% responded. The primary dose-limiting toxicity in all these trials has been flu-like symptoms, particularly fever and fatigue. Fever has generally resolved as treatment has been continued, but dosage reductions are usually necessary to alleviate fatigue. Future studies are likely to focus on the use of alpha interferon in combination with chemotherapeutic agents or other biologic response modifiers, such as monoclonal antibodies.
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PMID:Interferon therapy of non-Hodgkin's lymphoma. 349 59

The interferons are an important first member of a family of biologic response-modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Alpha interferon is the most extensively studied interferon species. Although antitumor activity has been seen both in vitro and in vivo in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. More than 90 percent of patients with hairy cell leukemia have a sustained recovery of their peripheral blood cell counts with alpha interferon therapy. Approximately 50 percent of patients with low-grade non-Hodgkin's lymphoma and cutaneous T cell lymphoma demonstrate a response to alpha interferon. More than 80 percent of patients with chronic myelogenous leukemia have a response to alpha interferon, and in one study, nearly half of the patients with response had complete suppression of the Philadelphia chromosome clone on at least one examination. Ongoing clinical trials are addressing such issues as optimal dosage, duration of alpha interferon therapy, and combinations of alpha interferon with other biologic agents, chemotherapy drugs, and radiation.
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PMID:Alpha interferon in the treatment of hematologic malignancies. 353 96

We have treated 25 patients, 7 with breast cancer and 18 with non-Hodgkin's lymphoma, with recombinant alpha 2 interferon. In 5 patients we observed cardiac arrhythmias that were unexpected and required treatment. No deaths have occurred that we can attribute to interferon, though 1 patient had to be resuscitated. Age, prior cardiac disease, prior treatment with doxorubicin, and interferon dose appear to be predisposing factors for this toxicity.
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PMID:Reversible arrhythmias observed in patients treated with recombinant alpha 2 interferon. 359 23

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

Clinical studies of combination therapy with chemotherapeutic agents and interferon (IFN) were performed. Seventeen patients with non-Hodgkin's lymphoma (NHL) and 2 patients with Hodgkin's disease (HD) were treated by combination chemotherapy (COPP or CHOP), and then received 300 X 10(4) U of alpha-IFN daily for 14 days. Complete remission was seen in 11 of 15 evaluable patients with NHL and both of 2 patients with HD. Myelosuppression such as leukopenia and thrombocytopenia was observed in half of the patients. Other side effects were fever, liver dysfunction, alopecia, and peripheral neuropathy. However, all these side effects were mild and well tolerated even in elderly patients.
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PMID:[A preliminary study of chemo-interferon therapy in malignant lymphoma]. 380 Apr 2

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
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PMID:The new alpha interferons. 391 Mar 84

Forty-nine patients with non-Hodgkin's lymphoma or Hodgkin's disease were entered into a multi-institutional phase II trial to evaluate the antitumor activity of human interferon alpha, prepared from buffy coats. Interferon alpha was administered intramuscularly in doses of 1 X 10(6) u, 3 X 10(6) u or 9 X 10(6) u daily for 30 days. Objective partial responses were seen in 3 of 18 patients with nodular lymphoma, all at the 9 X 10(6) u dose. Interferon alpha was not observed to be of therapeutic benefit in the other subtypes of non-Hodgkin's lymphoma or Hodgkin's disease. The major toxicities consisted of fatigue, fever, myalgias and weight loss. Serum interferon levels obtained 3 to 4 hours after injection varied widely, even among patients treated at the same dose level. Despite the relatively low doses of interferon used and the brief period of administration, this study extends the earlier observations of the antitumor effect of interferon in nodular lymphoma. These results are discussed in relation to the cumulative experience in human lymphoma using alpha interferons induced in human leukocytes and those produced in bacteria by recombinant DNA techniques.
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PMID:Human interferon alpha in malignant lymphoma and Hodgkin's disease. Results of the American Cancer Society trial. 402 69

Clinical trials of the antiviral action of interferon have shown an effect on the replication of several viruses including varicella zoster, herpes simplex, cytomegalovirus and hepatitis B. These studies indicate that administration early in the course of infection, or in some clinical circumstances, prophylactic administration, is likely to result in viral inhibition. The studies of interferon efficacy in topical application, as in prevention of recurrent herpes simplex keratitis, have shown limited efficacy except with very high doses. These studies are being pursued with more concentrated preparations of interferon. The evaluation of interferon in human malignancy is just beginning, but some encouraging results have been obtained in open trials of the drug in patients with non-Hodgkin's lymphoma, melanoma, osteogenic sarcoma, and other diseases. With newer methods for the production of interferon, it may be possible to evaluate its antiviral and anti-tumor effects in carefully controlled studies with larger numbers of subjects.
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PMID:Interferon as an antiviral and anti-tumor therapeutic agent. 616 51


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