Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry, biological activity, and pharmacokinetics of gamma-interferon and recombinant interferon gamma are reviewed, and the agent's clinical efficacy, adverse effects, and dosage and administration for the treatment of chronic granulomatous disease (CGD) and other disorders are described. Endogenous gamma-interferon is a 166-amino-acid protein encoded by a single gene on chromosome 12. Recombinant human interferon gamma is purified from Escherichia coli as a monomer containing 139 amino acids. Gamma-interferon has antiviral, immunomodulatory, and antiproliferative activity. Serum concentrations of recombinant interferon gamma increase in proportion to the dose. Clearance after i.m. or s.c. administration fits a two-compartment model. The half-life is 3.5-7.5 hours, and bioavailability is 89%. Evidence that recombinant interferon gamma can enhance phagocytic oxidative metabolism led to its evaluation for use in the treatment of CGD. Clinical studies showed that the agent decreases the frequency of serious infections in patients with CGD. Recombinant interferon gamma has shown only limited success in the treatment of metastatic renal cell carcinoma (RCC), both as a single agent and in combination with recombinant interferon alfa. Similarly, although interferons appear to be able to change cytogenetic abnormalities in some patients with Philadelphia chromosome-positive chronic myelogenous leukemia, therapy with recombinant interferon gamma has led to minimal success. However, the agent has produced some encouraging results in atopic dermatitis. The adverse effects of recombinant interferon gamma in patients with CGD usually consist only of fever, chills, headache, and erythema. The recommended dosage in CGD-afflicted children whose body surface area is greater than 0.5 sq m is 50 micrograms/sq m given by s.c. injection three times a week for life. Recombinant interferon gamma has given new hope to patients with CGD. Although the drug is very expensive, the cost may be offset by fewer hospitalizations to treat infection.
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PMID:Recombinant interferon gamma for treatment of chronic granulomatous disease and other disorders. 134 90

We analyzed toxicity and efficacy of second allogeneic hematopoietic stem cell transplantation (HSCT) or donor lymphocyte infusions (DLI) in 66 patients relapsing with acute myeloid leukemia (n = 15), acute lymphoblastic leukemia (n = 5), chronic myeloid leukemia (n = 14), non-Hodgkin's lymphoma (n = 14), myeloma (n = 8), myelodysplastic syndrome (n = 8), and metastatic renal cell carcinoma (n = 2). Forty-one patients were given second HSCT and 25 DLI. Sixteen patients (39%) are alive and disease-free after a second HSCT including 13 who had received nonmyeloablative conditioning. Thirteen patients (52%) are alive after DLI with mainly chronic myeloid leukemia patients in continuous complete remission. Relapse after HSCT is still a challenging situation and further studies to improve outcome of these patients are warranted.
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PMID:DLI or second transplant. 1261 Oct 68

Reduced-intensity hematopoietic stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than that of conventional HSCT. Favorable results have been reported particularly in hematological malignancies, such as chronic myelocytic leukemia and malignant lymphoma. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease and graft-versus-tumor remains unclear. More knowledge on the mechanism is crucial to enhance antitumor effect and to further improve the prognosis.
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PMID:Development of reduced-intensity hematopoietic stem cell transplantation in the National Cancer Center Hospital, Japan. 1292 7

Interferon (IFN)-alpha has demonstrated antitumor activity in a variety of solid and hematologic malignancies, including metastatic renal cell carcinoma. Pegylation, the process of combining a polyethylene glycol moiety to a biologic protein, substantially changes the pharmacokinetic profile of a drug, resulting in prolongation in half-life, increased area under the curve and, in some cases, improved efficacy. Pegylated IFN-alpha has been evaluated in chronic hepatitis C, chronic myelogenous leukemia and most recently in metastatic renal cell carcinoma. Registrational studies of pegylated IFN-alpha2a (PEGASYS) and pegylated IFN-alpha2b (PEG Intron) in patients with hepatitis C demonstrated greater efficacy with similar safety and tolerability to nonpegylated IFNs, with the advantage of less frequent administration. Studies evaluating these agents in the treatment of metastatic renal cell carcinoma and other cancers are ongoing.
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PMID:Evolving role of pegylated interferons in metastatic renal cell carcinoma. 1468 4

Numerous therapeutic options have been introduced for metastatic renal cell carcinoma (MRCC) in recent years, including monoclonal antibodies such as bevacizumab and small-molecule tyrosine kinase inhibitors such as sunitinib and sorafenib. Similarly, several other small-molecule inhibitors-including imatinib, dasatinib, and nilotinib-have been approved for the treatment of chronic myelogenous leukemia (CML). The combination of these targeted agents is an area of intense clinical investigation. Here, we describe a patient diagnosed with MRCC)while on imatinib therapy for cml. Treatment of this patient with the combination of bevacizumab and imatinib led to a 6-month period of stable disease, with no treatment-related adverse events. More extensive clinical exploration of this combination of agents may therefore be warranted.
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PMID:Concomitant renal cell carcinoma and chronic myelogenous leukemia: use of a targeted approach. 1937 Jan 79