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Biomedical subjects

J K Weick

Publications and source records attributed to J K Weick.

At least 37 records · Page 2Linked to original sources
PubMed1989

Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy.

The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan-Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis.

Adolescent↗
PubMed1988

Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

Adult↗
PubMed1988

Southwest Oncology Group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas.

The Southwest Oncology Group (SWOG) began testing doxorubicin-containing combination chemotherapy in 1972 using the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen. Subsequent studies, including 350 patients followed for up to 13.3 years, demonstrated that CHOP was curative in 32% of advanced stage, diffuse large cell lymphomas. More recently, promising results from several institutions suggest that new combinations including methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone (m-BACOD), prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate (ProMACE-CytaBOM), and methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B) may be superior to CHOP as gauged by complete response (CR) rates. Consequently, the SWOG developed a strategy to compare these regimens directly with CHOP. In 1984 the SWOG began testing these regimens in sequential group-wide phase II trials to confirm therapeutic activity, establish feasibility with regard to toxicity in a cooperative group setting, and gain experience using the complex schedules and dose-modification schemes. Those phase II studies have been completed, and preliminary results indicate that these regimens are active (CR rates, 53% to 65%) and feasible to administer in a cooperative group setting (fatal toxicity, 2% to 6%). We conclude that these three drug regimens can be administered safely in a cooperative group setting, and the CR rates support the current SWOG comparative trial using CHOP as the standard treatment arm.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Massive hemolysis in Clostridium perfringens infections.

Over a 14-month period at the Cleveland Clinic Foundation, 424 strains of Clostridium were isolated; of these, 52 strains were Clostridium perfringens isolated from 41 patients. Eight strains of C. perfringens were isolated from the blood of six patients; five of these patients had neoplastic disease and three developed massive intravascular hemolysis with rapidly developing shock and death. Clinical details are given on three patients with fatal Clostridium perfringens sepsis, and the nature of presentation and pathophysiologic mechanisms are discussed.

Blood Cell Count↗
PubMed1987

Phase II trial of sequential chemotherapy and low-dose radiotherapy in advanced gastric adenocarcinoma. A Southwest Oncology Group Pilot Study.

Thirty-four patients with metastatic gastric adenocarcinoma were treated with the combination of chemotherapy and radiation therapy in a Phase II trial. Induction chemotherapy consisted of one cycle of 5-fluorouracil (5-FU), adriamycin, and BCNU (FAB), followed in 4 weeks by a cycle of 5-FU, adriamycin and mitomycin-C (FAM). In responding and stable patients, consolidation radiotherapy to major sites of disease, followed by maintenance FAM, was administered. Twelve of 30 (40%) patients with measurable disease responded (3 complete responses and 9 partial responses), with a median response duration of 6.0 months. Toxicity was moderate and consisted of nausea, vomiting, and myelosuppression. No additive effects for this combined modality approach could be demonstrated.

Adenocarcinoma↗
PubMed1986

Phase I trial of intraperitoneal chemotherapy with 5-fluorouracil and citrovorum factor.

A Phase I trial of intraperitoneally administered 5-FU and citrovorum factor was performed in eight patients with a variety of malignancies. Both drugs were given according to a single weekly dose schedule in a volume estimated to be 2000 cc, including residual ascites. Citrovorum factor 50 mg was given first, immediately followed by 5-FU 1000-3400 mg, according to a dose-escalating schedule. Myelosuppression proved to be the dose-limiting toxicity, though mucositis, diarrhea, nausea, and abdominal pain were also produced. Six patients failed to respond to therapy. One patient with malignant mesothelioma showed a significant decrease in the production of malignant ascites and a transient conversion of peritoneal fluid cytologies from positive to negative, while a second patient with pancreatic cancer showed conversion of peritoneal fluid cytologies from positive to negative and demonstrated an objective partial response of an hepatic metastasis. Dosage adjustment according to body surface area would seem indicated by the toxicity data, with a 5-FU dose of 1200 mg/m2 body surface area and citrovorum factor 50 mg/m2 being recommended for Phase II trials of this combination of drugs given according to this weekly schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Inflammatory bowel disease and leukemia. A report of seven cases of leukemia in ulcerative colitis and Crohn's disease and review of the literature.

In a review of a large number of patients with inflammatory bowel disease, leukemia was observed in five patients with chronic ulcerative colitis and in two patients with Crohn's disease. In ulcerative colitis patients, there were three cases of acute myelocytic leukemia and one case each of acute lymphoblastic leukemia and chronic granulocytic leukemia. In Crohn's disease patients, there was one case each of chronic granulocytic leukemia and chronic lymphocytic leukemia associated with thrombocythemia. Sixteen other cases of leukemia have been reported to date in inflammatory bowel disease. All types of leukemia, but particularly acute myelocytic leukemia, have been described. There has been no single common feature as to type (whether ulcerative colitis or Crohn's disease), extent and course, or medical and surgical treatment of the bowel disease. The relative risk of leukemia in patients with ulcerative colitis was 5.3 [95% confidence interval 1.7 to 12.3 (P less than 0.01)] and of acute myelocytic leukemia 11.4 [95% confidence interval 2.3 to 24.9 (P less than 0.01)]. Our data on patients with Crohn's disease were not sufficient to assess the statistical significance of leukemia in this disease. This study suggests that there may be an increased risk of leukemia, particularly acute myelocytic leukemia, in ulcerative colitis. The causal relationship, if any, remains undetermined.

Adult↗
PubMed1986

Phase II evaluation of aclarubicin in refractory adult acute leukemia: a Southwest Oncology Group Study.

Aclarubicin, a new anthracycline antibiotic, was used to treat 24 adult patients with refractory adult leukemia, using a total dose of 300 mg/m2 (75 mg/m2/day X 4). There were 20 patients with acute myelogenous and four with acute lymphoblastic leukemia. Approximately two-thirds of the patients had a Karnofsky score of less than or equal to 2, and two-thirds had received two or more previous induction programs. Interim bone marrow evaluation was obtained in 18 of 30 remission induction courses and revealed marked hypocellularity in 14, inadequate specimens in three, and persistent disease in one. Seven patients received more than one course. Two patients refused further therapy. In patients with myelogenous leukemia, there were two complete remissions lasting 10 and 16 months and one partial remission lasting 4 1/2 months. There were no responders in patients with lymphoblastic leukemia. Toxicity included profound leukopenia and thrombocytopenia, moderate nausea and vomiting, diarrhea, and mucositis. There were no cardiac symptoms associated with the drug infusion, but there were three late events possibly associated with anthracycline cardiotoxicity. Used in this dosage schedule, aclarubicin is an active, but toxic, agent in the acute myelogenous leukemias.

Aclarubicin↗
PubMed1985

Effect of cis-diamminedichloroplatinum on erythropoietin production and hematopoietic progenitor cells.

Studies were conducted to determine whether the progressive development of anemia associated with the antineoplastic drug cis-diamminedichloroplatinum (cDDP) was the consequence of decreased erythropoietin (Epo) production due to cDDP-induced nephrotoxicity or selective inhibition of erythroid progenitor cells. Five days after a single intraperitoneal injection of cDDP, hypoxia-induced Epo production was not decreased in mice and was increased significantly in rats in spite of severe multifocal tubular necrosis. In both species, colony-forming units-granulocyte macrophage (CFU-gm) and colony-forming units-erythroid (CFU-e) were reduced significantly, with a greater decrease in CFU-e. Studies of an anemic patient receiving cDDP also showed elevated Epo and decreased CFU-gm and CFU-e. In vitro exposure of mouse and human bone marrow to cDDP caused a dose-dependent inhibition of CFU-gm and CFU-e in both species, with human CFU-e showing greatest sensitivity. The results indicate that the primary hematologic toxicity of cDDP is directed at the hematopoietic stem cell compartment.

Adult↗
PubMed1985

Magnetic resonance with marked T2-weighted images: improved demonstration of brain lesions, tumor, and edema.

The object of this study was to determine the sensitivity of magnetic resonance (MR) for imaging intracranial lesions with heavily T2-weighted images compared with that of computed tomographic (CT) and T1-weighted images. Fifty-five patients with known intracranial pathology consisting of primary neurogenic tumors, brain infarcts, demyelinating disease, and metastases were studied by MR and CT. Patients were studied with either 0.6 or 1.5 T systems with T1- and T2-weighted radiofrequency pulse sequences. The heavily T2-weighted images were found to be superior to the T1-weighted images in terms of sensitivity, with 168 lesions found versus 86 by CT and 104 by T1-weighted imaging.

Brain Edema↗
PubMed1985

Treatment of non-small cell bronchogenic carcinoma with vinblastine and mitomycin: a Southwest Oncology Group Study.

Forty-five patients with stage III M1 non-small cell bronchogenic carcinoma were treated with vinblastine (1 mg/m2 by iv bolus twice a day on 2 consecutive days) plus mitomycin (10 mg/m2 on Day 1). This treatment was repeated at 3-week intervals for three courses. Consolidation therapy with doxorubicin and cisplatin at doses of 50 mg/m2 each was administered to responders every 4 weeks for two courses, with subsequent vinblastine and mitomycin maintenance therapy every 6 weeks. Eleven partial remissions (24%) were achieved, with a median duration of remission of 16 weeks (range, 8-32) and a median survival of 19 weeks. No differences were seen in median duration of remission or survival by cell type or performance status.

Adenocarcinoma↗
PubMed1984

5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy.

Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.

Adenocarcinoma↗
PubMed1984

Antigenic phenotype of splenic hairy cells.

Hairy cell leukemia, a distinct clinical and morphologic lymphoproliferative disorder, is characterized by the proliferation of mononuclear cells of uncertain derivation. Attempts to identify the cell of origin have used studies either of functional capabilities or of membrane/cytoplasmic antigens. Only a few cases have been studied via monoclonal antibodies. Frozen sections of splenic tissue involved with hairy cell leukemia were studied with a variety of monoclonal antibodies having specificity for differentiation antigens using the avidin-biotinylated peroxidase complex technique. Conventional direct and indirect immunohistochemical study was used for immunoglobulin heavy and light chains. In all but one case, the neoplastic cells expressed monoclonal immunoglobulin. Although T cells were identified in persisting periarteriolar sheaths and occasionally admixed with red blood cells in pseudosinuses, phenotypic expression of intrathymic or peripheral T cell antigens by the proliferating neoplastic cells was not observed. Conversely, expression of B1 and HLA-Dr antigens by splenic hairy cells was documented in all 10 cases. Hairy cell leukemia cells did not express either monocyte antigens (M1 and MO2) or the antigens expressed by early (J5) and intermediate (B2) B cells or plasmacytoid lymphocytes and plasma cells (T10). These immunohistochemical results with monoclonal antibodies provide further evidence that hairy cell leukemia is characterized by a combination of antigens peculiar to mature B lymphocytes.

Antibodies, Monoclonal↗
PubMed1984

Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas.

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.

Antibodies, Monoclonal↗