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Biomedical subjects

J K Weick

Publications and source records attributed to J K Weick.

At least 55 records · Page 3Linked to original sources

Immunophenotypic characterization of acute leukemia by immunocytology.

The potential for specific immunophenotypic characterization of the acute leukemias has been enhanced greatly by the development of monoclonal antibodies. Currently, this immunologic data is obtained most commonly by flow cytometric analysis or cellular cytotoxicity assays. The former is an expensive technic that lacks morphologic evaluation unless cell sorting is performed. The latter precludes morphologic assessment by the nature of the assay. The authors have developed an immunostaining procedure utilizing cytospin preparations and immunoperoxidase methods that are relatively inexpensive and allow simultaneous assessment of the immunologic markers and cellular morphology. Although a comparison of flow cytometry and immunocytology revealed quantitative differences for individual cell surface markers, the "qualitative" immunologic phenotype of the leukemic population was virtually identical by the two technics.

Acute Disease↗

Colchicine in refractory chronic lymphocytic leukemia. A Southwest Oncology Group study.

Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicity was characterized by gastrointestinal intolerance in eight and thrombocytopenia in 12. There is activity of the drug in chronic lymphocytic leukemia but, as administered in this study, high dose therapy is not ideal and it may be more beneficial if the drug were given as low dose daily or weekly therapy.

Aged↗

The treatment of acute leukemia with continuous infusion L-Alanosine.

L-Alanosine, an antitumor antibiotic was administered by members of the Southwest Oncology Group (SWOG) to 22 patients with resistant acute non-lymphocytic leukemia. The drug was administered by continuous infusion for five days at a starting dose of 125 mg/m2/day. Mucositis was dose-limiting in 15 patients and no marrow aplasia was attained. As administered, L-Alanosine is not an effective single agent in acute leukemia.

Acute Disease↗

The combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation.

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. CHOP was given in the following manner: cyclophosphamide 400 mg/M2 IV day 1, adriamycin 40 mg/M2 IV day 1, vincristine 2 mg IV day 1, and Prednisone 100 mg po daily X 5. Forty-five rad total body irradiation was delivered in three fractions on days 21, 23 and 25. Chemotherapy was repeated on day 42, etc., until four cycles of CHOP and three cycles TBI (135R) were delivered. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. Two of the living patients are alive with disease and the remainder are in unmaintained remission. Two persons died with no response and one died in complete remission of an unrelated illness. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3,020 X 10(9)/microliters (range 1.2-5.5) and a mean nadir platelet count of 188 X 10(9)/microliters (range 016-270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients.

Adult↗

Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study.

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.002). Furthermore, the median survival was increased to 43 months with alternating combination chemotherapy as compared to 23 months with melphalan-prednisone (p = 0.004). After six to 12 months of induction therapy, 84 patients achieving remission were rerandomized to receive maintenance chemotherapy alone or with the addition of levamisole. The survival from the start of maintenance therapy was longer in patients receiving the added levamisole than with chemotherapy alone (p = 0.01). These findings support the use of aggressive multiagent chemotherapy for remission induction in patients with advanced-stage multiple myeloma.

Aged↗

Combination chemotherapy of metastatic thyroid cancer. Phase II study.

Eleven patients with metastatic thyroid cancer received combination chemotherapy with doxorubicin, bleomycin, vincristine, and melphalan. Six of 11 patients responded, two with a minor response, three a partial, and one with a complete response. Most responses were brief (2-3 months), but the patient with a complete response is alive and free of disease at 60+ months. Toxicity was moderate and predominantly hematologic. Thyroid carcinoma is a moderately sensitive neoplasm with occasional prolonged responses to chemotherapy.

Adult↗

Immunohistologic cellular phenotypes of lymphoproliferative disorders. Comprehensive evaluation of 564 cases including 257 non-Hodgkin's lymphomas classified by the International Working Formulation.

The plethora of classifications for non-Hodgkin's lymphomas (NHLs) and controversy regarding the merits of the individual classification schemes has led to the articulation of an International Working Formulation for NHL classification by a working group sponsored by the National Cancer Institute. This classification is based on both architectural and cytologic features and has been shown to have clinical relevance, but it is not an immunologic approach. With the use of frozen sections and both polyclonal and monoclonal antibodies, a comprehensive immunohistologic study was made of 564 biopsy specimens 1) for determination of the utility of the principle of monoclonality in differentiating benign from malignant lymphoproliferative disorders, 2) for definition of the immunohistochemical phenotypes of histologically benign and malignant cellular proliferations, and 3) for evaluation of the immunologic phenotype of 257 non-Hodgkin's lymphomas classified by the International Working Formulation. Two hundred seven "reactive benign" lymphoproliferations demonstrated polyclonal immunostaining. Monoclonal kappa light chain immunostaining was demonstrated in 3 of 4 cases classified as atypical hyperplasia, two of which had coexistent NHL or subsequently developed overt NHL. Frozen tissue sections were found to be essential for demonstration of immunoglobulin and glycoprotein membrane antigens. The results of immunohistochemical studies were readily integrated with the International Formulation. Although diffuse mixed and small lymphocytic lymphomas were immunologically heterogeneous (both T- and B-cell), follicular lymphomas were invariably of B-cell type, and immunoblastic lymphomas originating from homogeneous T- and B-cell populations were identified.

Antibodies, Monoclonal↗

Phase II study of amsacrine (m-AMSA) in advanced lymphomas: a Southwest Oncology Group study.

Amsacrine was administered to 73 evaluable patients with previously treated malignant lymphoma in the Southwest Oncology Group. The drug was administered iv every 3 weeks at a dose of either 90 mg/m2 to poor-risk patients (38 patients) or 120 mg/m2 to good-risk patients (35 patients) in 500 ml of 5% dextrose in water over 1 hour. The overall complete plus partial response rate is 16% (12 responses among 73 evaluable patients), with a response duration of 1-33 months. The dose-limiting toxic effect was myelosuppression, with leukopenia in 29 patients and thrombocytopenia in 18 patients. Our experience in the Southwest Oncology Group demonstrates the activity of amsacrine in malignant lymphoma.

Adolescent↗

Gallium nitrate in malignant lymphoma: a Southwest Oncology Group study.

Gallium nitrate was evaluated by the Southwest Oncology Group in 38 patients with malignant lymphoma, both Hodgkin's disease and non-Hodgkin's lymphoma. Treatment was administered every 2 weeks at a dose of 700 mg/m2, with acceptable toxicity. Seven partial responses (18%) with a duration of 3-11 months were seen: one of seven in Hodgkin's disease and six of 26 in diffuse non-Hodgkin's lymphoma. No responses were noted in nodular types. Gallium nitrate has activity in lymphomas and should be combined with more active drugs for patients who have undergone less intensive prior therapy.

Adolescent↗

Phase II trial of 5-fluorouracil, adriamycin, mitomycin C, and streptozotocin (FAM-S) in pancreatic carcinoma.

Twenty-five patients with unresectable and metastatic pancreatic carcinoma were treated with the combination of 5-fluorouracil, Adriamycin, mitomycin C and streptozotocin (FAM-S). Twelve of 25 patients responded (48%) and four patients demonstrated stable disease. Median survival of all patients was 6.75 months, and seven of 25 patients survived more than 12 months. Hematologic toxicity was moderate, and the predominant side effect recorded was nausea and vomiting (80% patients). Combination chemotherapy in pancreatic carcinoma may provide palliation and randomized trials are warranted to confirm these results.

Adenocarcinoma↗

Intermittent regional infusion of chemotherapy for pancreatic adenocarcinoma. Phase I and II pilot study.

Nineteen patients with unresectable and metastatic adenocarcinoma of the pancreas and ampulla of Vater were treated with intermittent regional infusion of the celiac axis (CAI) with the combination of 5-fluorouracil, adriamycin, mitomycin-C, and streptozotocin (FAM-S). Three schedules with escalating doses were investigated. The arterial infusion was repeated at 4 weeks, and in responding and stable patients, I.V. FAM-S was continued at monthly intervals. Twelve patients had measurable disease, and in this group one complete response and seven partial responses occurred. Median duration of response was 6+ months and median survival for all patients was 5.2 months. Four patients had catheter-related complications (emboli, three, sepsis, one). Hematologic and gastrointestinal toxicity was minimal. Celiac artery infusion with FAM-S in locally extensive and metastatic adenocarcinoma of the pancreas and ampulla of Vater is a relatively simple procedure associated with low incidence of serious complications and toxicity but a higher response rate than previously reported. Induction of response with CAI and subsequent maintenance therapy with intravenous chemotherapy is under investigation.

Adenocarcinoma↗

Extensive adenocarcinoma and large cell undifferentiated carcinoma of the lung treated with 5-FU, vindesine, and mitomycin (FEMi): a Southwest Oncology Group Study.

Sixty-three previously untreated patients with metastatic non-small cell lung cancer (40 patients with adenocarcinoma and 23 with large cell undifferentiated carcinoma) were treated with combination chemotherapy consisting of 5-FU (300 mg/m2) given as an iv bolus on Days 1-4 and vindesine (3 mg/m2) and mitomycin (10 mg/m2), both given as an iv bolus on Day 1 of each treatment course (FEMi). FEMi was repeated at 3-week intervals for three treatment courses and thereafter at 6-week intervals until disease progression. Major objective responses were seen in 13 of 63 patients (21%). Minor responses were seen in an additional 12 patients (19%). The median survival for all patients was 23 weeks and for responding patients was 38 weeks. The pretreatment performance status had a significant effect on both the response rate and survival time. Patients having an initial Karnofsky performance score greater than or equal to 70% had a 54% response rate, with a median survival of 42 weeks for responding patients. FEMi was well-tolerated: 18 patients (29%) did not have any side effects and only five (8%) experienced vomiting.

Adenocarcinoma↗

The use of cimetidine for the treatment of pruritus in polycythemia vera.

Thirty-four patients with polycythemia vera complicated by pruritus were treated with 900 mg of cimetidine daily for 30 days and their responses to treatment were evaluated. The conditions of 15 (44%) were improved, with 12 patients stating that pruritus completely disappeared. Nineteen patients either showed no improvement or had increasing symptoms. No toxic effects were reported. The positive responses seen are encouraging and suggest that controlled studies are indicated to further evaluate the effectiveness of H2 antagonists.

Cimetidine↗

Phase II trial of streptozotocin, mitomycin C, and 5-fluorouracil in adenocarcinoma of the pancreas.

A phase II study study employing 5-fluorouracil, mitomycin C, and streptozotocin in unresectable pancreatic carcinoma was performed. Seven of 22 patients (32%) responded and 4 of 22 (18%) had stable disease. Median survival of the entire group was 6 months, and of responders 9.5 months. In 13 patients with localized disease, five responses (38%) were seen and median survival was 7.5 months. Toxicity of the regimen was moderate, being predominantly gastrointestinal and renal. The usefulness of this regimen in localized pancreatic cancer should be explored further.

Adenocarcinoma↗

Cutaneous macroglobulinosis.

A patient with Waldenström's macroglobulinemia had firm, translucent papules and nodules on the extremities. Clinically, the skin lesions were suggestive of amyloidosis cutis. Histologically, a homogeneous eosinophilic material was observed in the upper dermis and encasing the hair follicles. Special histochemical stains, electron microscopy, and immunofluorescence microscopy identified the material as IgM.

Amyloidosis↗