Biomedical subjects

M L Keohan

Publications and source records attributed to M L Keohan.

5 recordsLinked to original sources

PubMed2000

Peritoneal mesothelioma.

Malignant peritoneal mesothelioma is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatments are unsatisfactory, and new approaches are needed. We have noted prolonged survival in selected patients after intensive multimodality treatment. Our current experimental regimen includes initial laparotomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Port-a-Caths (Sims Deltec, Inc., St. Paul, MN); repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy and intraoperative hyperthermic perfusion with mitomycin and cisplatin; and whole abdominal radiation. Patients with peritoneal mesothelioma who are not candidates for this approach can sometimes be palliated with systemic (intravenous) chemotherapy using doxorubicin or mitomycin, alone or in combination with cisplatin or carboplatin. Newer agents such as gemcitabine and multitargeted antifolate (pemetrexed disodium, LY231514) show promise of greater effectiveness.

Antineoplastic Agents↗

PubMed2000

Gemcitabine for relapsed or resistant lymphoma.

BACKGROUND: Gemcitabine therapy has not been widely assessed in the treatment of hematological malignancies. We have examined the efficacy and safety of gemcitabine in patients with relapsed or resistant lymphoma. PATIENTS AND METHODS: Gemcitabine (1 g/m2) was given weekly for 7 consecutive weeks, followed by a week off treatment. The drug was then given for 3 consecutive weeks, followed by a week off treatment; this regimen was continued until disease progression or drug intolerance. Fifteen patients have enrolled. Most have been extensively pre-treated for advanced diffuse large-cell or mantle-cell lymphoma. RESULTS: The drug was well tolerated; no patient suffered treatment-related sepsis, hemorrhage or death. Non-hematopoietic toxicity led to discontinuation of gemcitabine therapy in two patients. Dose reductions or delays were required for about two-thirds of treatments. Of 13 evaluable patients, one had a complete response, 3 a partial response, 3 stable disease, and 6 disease progression. After 6 infusions of gemcitabine, a patient with advanced Hodgkin's disease has had a complete remission lasting 21 months. CONCLUSIONS: Gemcitabine has substantial activity and acceptable toxicity in heavily pre-treated patients with advanced lymphoma. Further study is warranted.

Aged↗

PubMed1997

A phase II Southwest Oncology Group study of cisplatin and continuous infusion vinblastine in the treatment of advanced soft tissue sarcoma.

PURPOSE AND METHODS: Bone and soft tissue sarcomas currently comprise 1% of adult malignancies and 15% of pediatric malignancies [1]. While doxorubicin and ifosfamide are active agents, no significant impact on survival has been observed. More active regimes are required in sarcoma. This trial studied cisplatin and a 5 day continuous infusion of vinblastine for patients who had had disease progression of advanced soft tissue sarcoma after a doxorubicin based regimen. RESULTS: Between July 1983 and October 1986, 20 patients entered the study. There were no treatment related deaths. Seven patients required dose adjustment for neutropenia. No responses were observed.

Adult↗

PubMed1997

Chemotherapy for advanced sarcoma: therapeutic decisions and modalities.

In patients who have advanced soft tissue sarcoma that is no longer localized, systemic chemotherapy is the most reasonable option for treatment. The decision to treat or to use experimental or conventional agents should be based on the clinical assessment of anticipated net benefit in quality of life as well as the remote possibility of complete remission or even cure. Asymptomatic elderly patients with relatively stable disease might best be treated with watchful waiting; whereas younger excellent-performance-status patients should be offered the opportunity of participating in phase II or phase I studies of newer drugs and intensification regimens. Of the currently available single agents, only doxorubicin (or epirubicin) and ifosfamide show response rates greater than 20%; both show a definite dose-response relationship. Dacarbazine shows particular activity in uterine leiomyosarcomas. Combination chemotherapy regimens such as doxorubicin-ifosfamide show a higher response rate, but may be more toxic. New agents are needed. The current progress in our understanding of the molecular biology of sarcomas, and our expanded comprehension of the mechanism of action of cytotoxic drugs and the biology of drug resistance is cause for optimism.

Antineoplastic Agents↗

PubMed1985

Phenotype of recovering lymphoid cell populations after marrow transplantation.

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗