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)

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.
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PMID:Phase I pharmacologic study of a new Vinca alkaloid: navelbine. 401 23

At Saitama Cancer Center a Phase II study of Vindesine was carried out in 18 patients with hematological malignancy being refractory to standard chemotherapies. Vindesine (VDS) was given weekly at a dose of 3 mg/m2 as single-agent chemotherapy. One cytoreduction effect (CE) in 5 patients with acute lympho blastic leukemia, two CEs in 2 patients with acute non-lymphocytic leukemia, one PR and one CE in 4 patients with CML/BC, three PRs in 3 patients with diffuse non-Hodgkin's lymphoma (NHL) of large cell type, one CR in 2 patients with lymphoblastic lymphoma and one PR in 2 patients with Burkitt's lymphoma were obtained. VDS was discontinued in two patients because of neurologic toxicities such as incontinence of urine, abdominal distension, and severe constipation.
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PMID:[Phase II study of Vindesine in patients with hematological malignancy]. 634 82

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
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PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

Intensive cytoreductive therapy may be curative in certain hematopoietic malignancies, but its administration is limited by lethal marrow toxicity. Bone marrow transplantation (BMT) provides a way of rescue from this toxicity. The donor may be a human leukocyte antigen (HLA) "matched" sibling (allogeneic), an identical twin (syngeneic), or the patient (autologous). Long remissions and possible cures of 50% to 60% have been reported in acute leukemia after intensive treatment with chemotherapy, with and without total body irradiation, followed by allogeneic BMT. A similar approach has been used in chronic myelocytic leukemia (CML) and in non-Hodgkin's lymphoma with encouraging results. Results are best in younger patients and those transplanted early in their disease (i.e., in the first remission for acute leukemia and in the chronic phase of the disease in CML). Solutions to major problems associated with allogeneic BMT, such as graft-versus-host disease and viral infections, are being actively pursued. Syngeneic BMT avoids some of the above problems, but relapses appear to be greater. Nevertheless, this approach has produced a significant number of cures. Autologous BMT is the newest approach, and the demonstration that marrow may be purged of residual tumor cells by immunologic or pharmacologic means has engendered enthusiasm for this area of clinical therapeutic investigation.
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PMID:Bone marrow transplantation in leukemia. Current status. 638 15

A clinical study of a new semisynthetic podophyllotoxin etoposide (NK 171) was performed in patients with various hematological malignancies refractory to standard chemotherapies. The drug was given intravenously in a dose of 100-130 mg/m2/day for five days or orally in a dose of 130-170 mg/m2/day for five days. Out of 9 patients with non-Hodgkin's lymphoma, 2 CR and 4 PR were obtained; out of 4 acute nonlymphoblastic leukemias, 1 CR, and out of 4 chronic myerogenous leukemias 2 CR and 1 PR, were obtained. The dose limiting factor was leukopenia, and alopecia was frequent while other hematologic and gastrointestinal toxicities were mild. Etoposide (NK 171) had no clinical cross resistance to other antitumor agents, thus warranting further clinical trials, in combination chemotherapy against NHL, ANLL and CML-BC.
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PMID:[Phase II study of etoposide (NK 171) in advanced hematological malignancies]. 647 35

The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease. Eight cases of acute nonlymphocyctic leukemia, one case of chronic myeloid leukemia, three cases of non-Hodgkin's lymphoma, three cases of sarcoma, and 19 other tumors were identified. The ten-year estimated risk of leukemia by treatment was the following: radiotherapy only (0), chemotherapy only (0.02), initial combined radiotherapy-chemotherapy (0.06), and salvage combined radiotherapy-chemotherapy (0.09). The ten-year estimated risk of solid tumors was 0.07 overall, with all treatment groups associated with similar risks. Unlike some other reports, a greater risk of leukemia in patients who began treatment for Hodgkin's disease at age 40 or older was not found. However, a positive association was noted between increasing risk of solid tumors and increasing patient age.
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PMID:Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience. 654 79

Nineteen patients with advanced refractory lymphoma and 12 patients with acute leukemia, including seven in blastic crisis of chronic myelogenous leukemia (CML), were treated with vindesine in combination with prednisone. Of 16 evaluable patients with lymphocytic or histiocytic lymphoma, one achieved complete remission (6%) and eight achieved partial remissions (50%). Median duration of response was 12 weeks (range, 4-72+). Four of six evaluable patients in blastic crisis of CML showed definite improvement in blood cell counts and symptoms. The major dose-limiting toxic effect was bone marrow suppression, while neurotoxicity was seldom cause for dose modification. The study shows vindesine and prednisone to be active in heavily pretreated patients with non-Hodgkin's lymphoma and blastic phase of CML.
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PMID:Combination of vindesine and prednisone in malignant lymphoma and acute leukemia. 657 59

Immune complexes (IC) were examined in the sera of 100 patients with histologically confirmed non-Hodgkin's lymphoma (NHL) and 80 leukemic patients by the EA-rosette forming cell inhibition assay. Sera from 55 healthy controls were also tested for the presence of IC. Using 9% rosette inhibition as a base-line, IC were observed to be present in 66 out of 100 sera from patients with NHL (66%), 35 out of 80 sera from patients with leukemia (43.7%) and 10 out of 55 control subjects (18%, p less than 0.001). The percentage of positive results was significantly lower in NHL patients with favorable prognosis (45%) than in patients with unfavorable prognosis (80%). IC from the sera of 7 ALL and 6 CML patients were investigated before chemotherapy, in remission and at relapse. The mean inhibitory rate of rosette inhibition was significantly higher in patients during the blastic stage of leukemia than during the complete remission (12.5%), and later it became higher again at the time of relapse. In CML patients, the previously normal serum rosette inhibition activity increased during the blastic crisis. These observations indicate that the follow-up studies of such patients may determine their prognosis accurately.
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PMID:Circulating immune complexes in patients with lymphomas and leukemias. 658 80

Philadelphia chromosome-positive cells with a standard translocation (9;22) were found in bone marrow and peripheral blood samples from a patient with non-Hodgkin's lymphoma (immunoblastic sarcoma) in the final leukemic phase. The neoplastic clone was of monoclonal B-cell character with surface Ig (mu, kappa) and mouse red blood cell receptors. This is the first case with surface Ig and t(9;22) cells reported without evidence of chronic myeloid leukemia. Also, additional consistent chromosome aberrations were found.
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PMID:Patient with B-cell neoplasia (immunoblastic sarcoma) and the Philadelphia chromosome. 660 9

Serum levels of immunosuppressive acidic protein (IAP) in 105 patients with hematopoietic malignancies, there were 12 cases of acute myeloblastic leukemia, 1 acute monocytic leukemia, 13 myelomonocytic leukemia, 4 acute promyelocytic leukemia, 26 chronic myelogenous leukemia, 22 non-Hodgkin's lymphoma, 5 Hodgkin's disease, 6 adult T-cell leukemia, 5 acute lymphoblastic leukemia, 3 chronic lymphocytic leukemia, and 8 multiple myeloma. High levels of serum IAP were detected in all of the patients except chronic phase of CML, malignant lymphoma in stage I and II, and multiple myeloma. In the cases of malignant lymphoma, serum IAP levels in stage III and IV were higher with statistical significance (p less than 0.01) than those in stage I and II. Serum IAP levels in the patients with CML in blastic crisis were higher than in the chronic phase, so serum IAP levels are useful as one diagnostic parameters in blastic crisis. However, in patients with ANLL in relapse, serum IAP levels showed normal values. Serum IAP levels paralleled those of acute phase reactants such as alpha 1-acid glycoprotein , C-reactive protein, alpha 2-globulin, and alpha 1-antitrypsin, and had inverse correlations with PPD and PHA skin test.
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PMID:[Quantitative measurement and clinical analysis of serum levels of immunosuppressive acidic protein (IAP) in hematopoietic malignancies]. 673 51


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