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.
 ...
PMID:Recombinant interferon gamma for treatment of chronic granulomatous disease and other disorders. 134 90

We demonstrated the clinical effectiveness of recombinant interferon-gamma (rIFN gamma) (Biogen) in 18 patients with Philadelphia-positive chronic myeloid leukemia. Sequential cytogenetic studies and molecular analyses of the breakpoint cluster region and for immunoglobulin and T cell rearrangements were performed every 3-4 months. In 13 patients who received treatment for a minimum of 3 months, the majority were treated with 1.5 mg/m2, t.i.w., i.v. Nonhematologic effects--particularly chills, rigors, myalgia, fatigue, headaches, and nausea--were significant. Complete or partial hematologic responses were observed in six patients, two of whom had approximately 20% normal metaphases after an average of 74 weeks of treatment. However, reversion to 100% Ph+ cells occurred 30 weeks later. In these two patients, in whom normal metaphases were found, no changes were observed in the presence of rearrangements of the breakpoint cluster region. In addition, the marrows remained hypercellular, and the leukocyte alkaline phosphatase score and B12 levels remained abnormal. No immunoglobulin or T cell beta-chain gene rearrangements were found. These data indicate the clinical effectiveness of rIFN gamma in some patients with chronic myeloid leukemia, although the fundamental nature of the disease is unaltered by this form of treatment.
 ...
PMID:Recombinant gamma-interferon has activity in chronic myeloid leukemia. 215 24

The administration of recombinant human interleukin-1 beta (rhIL-1 beta) stimulates pluripotent cell growth and reduces mortality from infection in animal models. In this phase I trial, rhIL-1 beta (0.02-0.50 microgram/kg) was administered by 30-minute intravenous infusion once daily for 2 or 5 consecutive days. The dose was escalated with the subsequent cycle in the same patient if no hematologic response was observed. Nineteen patients with severe bone marrow failure received 60 courses of IL-1 beta. Diagnoses included autologous bone marrow transplant (BMT) (n = 5), allogeneic BMT (n = 7) or idiopathic aplastic anemia (n = 6) and 1 patient with chronic myeloid leukemia. Toxicities included fever (89%), chills (85%), hypertension (89%), hypotension (57%) and headache (95%). No complications were life-threatening and all either spontaneously resolved or were managed pharmacologically. In 8 of 19 patients there was an acute, transient increase in neutrophil counts. In 2 patients there was a transient increase in platelet count; however, no durable, clinically significant effects on peripheral blood counts were observed. In conclusion, administration of rhIL-1 beta in this population of patients had limited efficacy and moderate toxicity.
 ...
PMID:Phase I study of recombinant human interleukin-1 beta (rhIL-1 beta) in patients with bone marrow failure. 785 32

The safety, tolerance, and clinical effects of combined therapy with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (rIL-2) administered subcutaneously for 2 courses of 4 weeks each, with 4 weeks interval between courses, given as outpatient therapy have been assessed in 10 patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML). All patients were previously treated with conventional chemotherapy and 3 failed to respond to IFN-alpha administered prior to our study. Median duration of disease from diagnosis was 36 months. Seven patients were in first chronic phase and the other 3 were in blast crisis, second chronic phase, and relapse post-bone marrow transplantation (BMT), respectively. Hematological response (median follow-up 16 months) was observed in 9 patients, with a decline in number of white blood cells and platelets. Elimination of Ph1 was observed in the patient who relapsed post-BMT with complete elimination bcr/abl RNA by polymerase chain reaction. Rebound lymphocytosis and eosinophilia were observed in most of the patients. Toxicity was acceptable. The main adverse effects were fever, chills, fatigue, anorexia, nausea, and vomiting. The side effects were reversible and no interruption of treatment was required. There was no treatment-related hospitalization or deaths. These data suggest that simultaneous subcutaneous IFN-alpha and rIL-2 home therapy is feasible, reasonably well tolerated, and potentially beneficial in CML patients. These observations may have important implications for the treatment of minimal residual disease following allogeneic and autologous marrow transplantation.
 ...
PMID:Treatment of chronic myelogenous leukemia with recombinant human interleukin-2 and interferon-alpha 2a. 792 12

A 59-year-old man with chronic myelogenous leukemia (CML) had a white-blood-cell (WBC) count of 55,400/microliter when admitted in July 1997, and was placed on oral hydroxyurea (HU) of 1,500 mg/day. Treatment with 600 MU/day of interferon alpha (IFN alpha) was started on August 5. HU was discontinued when the patient's WBC count dropped to 8,100/microliter on August 18. However, HU was resumed about a month later, after his WBC count increased to 10,100/microliter, but discontinued when the patient started to complain of chills, high fever, and bilateral femoral pain. HU treatment was initiated again one week later, after the patient's WBC count had begun rising but ceased again after he experienced chills, high fever, and bilateral femoral pain. The patient's myogenetic enzymes were found to be increasing the following day, and a lymphocyte stimulation test (LST) with HU showed a high stimulation index of 41.7%. The elevation of myogenetic enzymes and the results of the LST suggested that myositis due to HU was the cause of the patient's clinical manifestations. His myositis spontaneously disappeared after HU was discontinued. Although the patient is no longer receiving HU, IFN alpha has brought his CML under control. To our knowledge, this is the first reported case of myositis caused by HU.
 ...
PMID:[Myositis caused by hydroxyurea in a patient with chronic myelogenous leukemia]. 979 2

Nine patients with onco-hematological malignancies with a poor prognosis due to high risk of relapse received immunotherapy with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) s.c. as maintenance therapy after receiving autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT). All the patients were considered at very high risk of relapse. We attempted to assess the efficiency, toxicity and clinical effects of these cytokines in these patients. Five patients were treated with high-dose of IL-2 and the other four patients with escalating doses every month. Side-effects in the first group of patients consisted of fever, chills, weakness, nausea, anorexia, loss of weight and local dermatitis in the injection site. Toxicity on the WHO scale was grade II in three patients and grade IV in the other two patients. In the second group of patients, the same clinical signs of toxicity appeared, but these were grade I on the WHO scale in all patients. None of the patients had infections or died in relation to administration of IL-2. Four patients died of relapse or progression of their hematological malignancies. The other five patients are alive, one in chronic phase of CML and the other four patients are in complete remission of their malignancies.
 ...
PMID:Treatment with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) after autologous bone marrow or peripheral blood stem cell transplantation in onco-hematological malignancies with a high risk of relapse. 1019 3

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.
 ...
PMID:Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres. 1197 21

The present work focuses on the therapeutic efficacy and the toxicity of alpha interferon in patients younger than age 18 years. 5 patients younger than 18 years were treated and followed up between 1990 and 1999 at the department of haematology (Aziza Othmana Hospital) Hydroxyurea was given as initial treatment to all patients. After a median period of 8 months, these patients received alpha interferon (5 millions units/m2 once). Six months after the beginning of the alpha interferon a complete hematologic response was obtained in all patients. The median overall survival was of 66 months: 3 patients are still alive (2 patients in an advanced stage and one patient in chronic phase) and 2 patients died after transformation. The most common reported side effects of alpha interferon were asthenia, weight loss, fever, myalgia, chills and headaches--these toxic manifestations were mild and were noticed in all our patients. Myelosuppression was noted in two patients. Interferon is well tolerated in patients younger than age years 18 old, with CML. It may offer an alternative to bone marrow transplantation in children in the chronic phase of CML without histocompatible donor. The role of new agents such as STI 571 needs to be evaluated as well.
 ...
PMID:[Alpha interferon in children with Philadelphia chromosome-positive chronic myeloid-leukaemia]. 1604 5

A 57-year-old woman with chronic myeloid leukemia showing severe basophilia (WBC 17.1 X 10(9)/L, basophils 23%) was treated with 400mg imatinib in June 2003. A high basophil count (WBC 10.6 X 10(9)/L, basophils 31%) was still observed after 1 week of therapy. After 9 days of therapy, she developed generalized pruritic skin erythema, chills and high fever. After terminating imatinib treatment, prednisolone therapy was initiated. The rash quickly disappeared. Four days after withdrawal of imatinib, leukocyte count was 13.0 X 10(9)/L with 3% of basophils, suggesting the possibility that rapid decrease in basophils following imatinib therapy may induce severe cutaneous reactions.
 ...
PMID:[Generalized erythema triggered by a rapid decrease of basophils in chronic myeloid leukemia treated with imatinib]. 1644 Aug 9