Search PubMed⌕ Search

Biomedical subjects

J A Libnoch

Publications and source records attributed to J A Libnoch.

At least 19 recordsLinked to original sources
PubMed1991

Evaluation of continuous infusion low-dose 5-azacytidine in the treatment of myelodysplastic syndromes.

The treatment of myelodysplastic syndromes (MDS) is both difficult and controversial. In the current study, we evaluated the efficacy of low-dose 5-azacytidine in the treatment of this disorder. Fifteen patients with MDS were entered on study to be treated with 5-azacytidine by continuous intravenous infusion for 14 days. Doses of the drug ranged from 10 mg/m2/day to 35 mg/m2/day, with most patients receiving 16.5 mg/m2/day. In two patients, the drug was stopped early in the course of treatment because of thrombocytopenia. Thirteen patients completed therapy according to protocol. Three of 13 patients demonstrated a partial response to therapy. Of these three patients, one had an increase in platelet and absolute neutrophil counts, while the other two no longer required support with red cell transfusions. The drug was well tolerated and significant myelosuppression did not occur in most patients. Low-dose 5-azacytidine appears to have activity in the treatment of primary MDS and future studies should consider evaluation of this drug in combination with hematopoietic growth factors.

Adult↗
PubMed1991

Continuous 5-fluorouracil infusion and alpha interferon in advanced cancers: a report of initial treatment results.

Twenty-four patients with advanced metastatic cancer were treated with continuous intravenous 5-fluorouracil infusion 200-300 mg/m2/day and alpha interferon 3 million units subcutaneously 3 times per week. The average duration of treatment was 87 days (range 22-204 days). 5-fluorouracil could be infused 66% of the planned time on treatment, and patients received an average of 60% of the planned interferon injections. Objective tumor responses were seen in 6 of 17 previously untreated patients (35%). Twenty-two of the 24 patients (92%) experienced toxicity (greater than or equal to ECOG grade II) that required treatment interruption and subsequent dose reduction predominantly for the following reasons: mucositis (67%), hand-foot syndrome (21%), and leukopenia (25%). The incidence of treatment limiting toxicity is higher than previously observed with 5-fluorouracil infusion alone. This suggests true augmentation of 5-fluorouracil effect by interferon. 5-Fluorouracil infusion and alpha interferon is a potentially useful combination that needs further evaluation in future phase II and phase III trials.

Adult↗
PubMed1990

5-Fluorouracil infusion and low-dose weekly cisplatin: an analysis of increased toxicity.

It has been suggested that the addition of weekly low-dose cisplatin (DDP) may potentiate the efficacy of continuous infusion 5-fluorouracil (5-FU) without adding significant toxicity. To investigate the extent of added toxicity, an analysis of toxicity was completed in 18 patients with advanced cancers treated with continuous ambulatory 5-FU infusion 300 mg/m2/day and weekly low-dose cisplatin (DDP) 20 mg/m2. Ten of the 18 patients (56%) developed multiple (four or more) toxicities during treatment. In addition, toxicity categorized as severe occurred in 10 patients (56%). Seventeen of the 18 patients (94%) required treatment interruption or dose attenuation due to toxicity and most patients experienced a decline in Eastern Cooperative Oncology Group performance status due to treatment-related toxicity. Compared with historical toxicity patterns when 5-FU infusion is administered alone, the addition of DDP has resulted in significant increases in nausea and vomiting, anorexia, diarrhea, stomatitis, and myelosuppression. The addition of low-dose weekly DDP adds significant toxicity and morbidity to the continuous 5-FU infusion regimen.

Adult↗
PubMed1987

Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report.

A randomized, prospective trial utilizing cisplatin and fluorouracil as neoadjuvant chemotherapy in the treatment of advanced squamous cell carcinomas of the upper aerodigestive tract was initiated in January 1983. Sixty patients were stratified by site (oral cavity, 19; larynx, 14; hypopharynx, 14; oropharynx, 11; nasopharynx, one; and paranasal sinuses, one) and by stage (III, 19; IV, 41), and then randomized to receive either standard treatment (defined as preoperative irradiation followed by radical excision or irradiation alone) or adjuvant chemotherapy followed by standard treatment. An additional three patients were entered into the study, but withdrew. Chemotherapy consisted of three cycles for those patients in whom an objective tumor response was observed; nonresponders received standard treatment. Response to chemotherapy was complete in five and partial (greater than 50%) in 18 patients, for an overall response rate of 85%. The follow-up for surviving patients was a minimum of 24 months and a maximum of 44 months. Survival was compared for patients in both treatment groups according to the method of Lee and Desu. Despite excellent tumor response, actuarial survival was 70% in the standard treatment group as opposed to 56% in the experimental group. It was therefore evident that the high response rates reported in previous pilot studies do not necessarily result in improved survival in these cancers.

Carcinoma, Squamous Cell↗
PubMed1987

Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study.

A prospective, randomized, controlled, double-blind study was performed between 1982 and 1985 to assess the ability of ketoconazole to prevent fungal infections in selected patients with cancer. Fifty-six patients receiving induction chemotherapy for acute leukemia, autologous bone marrow transplant for refractory nonhematopoietic malignant neoplasms, multidrug chemotherapy for malignant lymphoma, or corticosteroids for brain metastases were randomized to receive either oral ketoconazole, 400 mg/d, or placebo and observed until leukopenia resolved or corticosteroid therapy was stopped. Oral candidiasis developed in eight (28%) of 29 patients receiving placebo compared with none of 27 receiving ketoconazole. However, ketoconazole failed to prevent Candida esophagitis and vulvovaginitis in two patients and one patient, respectively. Furthermore, prophylactic use of ketoconazole did not significantly alter the total number of hospital days, febrile days, or antibiotic days or the requirement for amphotericin B in patients with acute leukemia and autologous bone marrow transplant. Since oral candidiasis can be successfully managed by several different treatment modalities when it does occur, we do not think that the routine prophylactic use of ketoconazole is justified.

Candidiasis↗
PubMed1986

Correlation of circulating natural killer cell count with prognosis in large cell lymphoma.

A monoclonal antibody recognizing a natural killer (NK) cell-associated antigen was used to sequentially quantify numbers of peripheral blood NK cells in a small group of patients with large cell lymphoma. Patients with active disease had low numbers (less than 100/mm3) of NK cells. Patients in complete remission after therapy had normal numbers of NK cells, but those patients who relapsed had a fall of NK cell number to less than 100/mm3 preceding or concurrent with clinical relapse. A role for NK cells in the surveillance and control of abnormal lymphoproliferation is suggested, as is the possible prognostic utility of sequential peripheral blood NK cell quantification in patients with large cell lymphoma.

Antibodies, Monoclonal↗
PubMed1986

Immunoregulatory abnormalities in myelodysplastic disorders.

Immunoregulation was assessed in a group of patients with myelodysplasia (MDS) by flow cytometric analysis of peripheral blood lymphocyte subsets and in vitro studies of mitogen-stimulated T-lymphocyte blastogenesis. Mitogenesis was significantly depressed in MDS patients compared to controls (p less than .001) and a similar defect was found in a small group of patients with untreated acute nonlymphocytic leukemia (ANLL) (p less than .005). The impaired mitogenic response ability of T-cells in these patients did not appear to be the result of alteration in lymphocyte subpopulation ratios. The observed defect might result from defective cooperation between T-lymphocytes and abnormal myeloid elements. Alternatively, the lymphocytes themselves could be derived from the abnormal clone and thus be functionally abnormal.

Antigens, Surface↗
PubMed1986

Myeloid cell surface phenotype in myelodysplasia: evidence for abnormal persistence of an early myeloid differentiation antigen.

A panel of monoclonal antibodies recognizing myeloid cell surface differentiation-associated antigens was used to study the peripheral blood myeloid population of 23 patients with myelodysplastic syndromes (MDS) and 23 controls. A marker for immaturity, defined by the presence of the antigen recognized by the My9 antibody, was found to persist on the surface of mature neutrophils in a subgroup of MDS patients. Abnormal My9 positivity was concentrated primarily, but not exclusively, in previously described morphologically defined subgroups of MDS patients considered to be at highest risk for leukemic conversion. Longitudinal study of a larger number of patients will be required to test the hypothesis that abnormal persistence of My9 may have prognostic significance.

Antibodies, Monoclonal↗
PubMed1986

Prognostic influence of TNM staging and LDH levels in small cell carcinoma of the lung (SCCL).

To better define the prognostic factors influencing the response to therapy and survival in small cell carcinoma of the lung (SCCL), an expanded "TNM" type staging system was developed and investigated in a series of 73 protocol treated patients. Because serum LDH levels at disease presentation have been correlated to disease extent, response to therapy, and treatment outcome in a number of malignancies, including SCCL, these interrelationships were also analyzed in the protocol patients. The TNM system was found to be a more descriptive and specific "shorthand" for denoting sites of involvement and for indicating the body burden of tumor than the traditional limited-extensive disease (LD-ED) system. A clear statistical advantage could not be shown over the LD-ED system for predicting chemotherapy response or survival, although there were trends suggesting the TNM system could divide patients into three prognostic subgroups. Serum LDH proved to be a useful index of disease extent and therapy outcome. LDH levels at presentation were proportionately higher with more extensive tumor, measured by either the LD-ED or TNM staging. High LDH predicted poorer responses to chemotherapy and lower survival within similar stage subgroups compared to patients with normal LDH levels. The negative effect of elevated LDH was independent of hepatic involvement and did not predict subsequent hepatic failure in any consistent way. The SCCL TNM staging system proposed needs further refinement and should be tested with larger patient numbers. LDH, along with other tumor markers recently identified, need to be integrated into the staging system to form an overall prognostic index.

Aged↗
PubMed1985

Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma.

The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors' previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals. It is concluded that radionuclide studies of brain, liver-spleen, and bone can be eliminated and can be replaced by CAT scan of brain, chest, and abdomen. Site of recurrence indicate that most intrathoracic recurrences took place outside the radiation therapy field and in the pleural space. An incidental finding was the high incidence of intramedullary spinal cord recurrence.

Adult↗
PubMed1985

Prolonged survival in Richter syndrome with subsequent reemergence of CLL: a case report including serial cell-surface phenotypic analysis.

The development of a large cell lymphoma in a patient with chronic lymphocytic leukemia (Richter syndrome) is associated with a poor prognosis. There is dispute regarding the clonal origin of the large cell component. We described a patient in whom prolonged remission of the large cell component was achieved with combination chemotherapy, followed by subsequent reemergence of the less aggressive CLL clone. Serial cell surface phenotypic data are presented suggesting origin of both histologies from a common B-cell clone.

B-Lymphocytes↗
PubMed1985

Multiagent chemotherapy, prophylactic neuraxis irradiation, and consolidative irradiation for small cell carcinoma of the lung.

Between 6/81 and 6/83, 73 patients with small cell carcinoma of the lung were treated according to a prospective protocol in which cyclophosphamide, doxorubicin, and vincristine (CAV) were given concurrently with prophylactic craniocervical irradiation to the level of C5. Both limited and extensive disease patients with normal computed tomography of the brain received 25 Gy in 10 fractions in 2 weeks. Complete responders to CAV received consolidative thoracic irradiation (CTI) to the local-regional primary (37.5 Gy in 15 fractions in 3 weeks), the first 25 Gy in 10 fractions serving as prophylaxis of the C6 to T12 spinal cord. The neuraxis from L1 to S2 then received 25 Gy in 10 fractions in 2 weeks. Consolidative irradiation of localizable metastatic sites was given in extensive disease patients. Partial and nonresponders to CAV received 50-60 Gy in 5-6 weeks to local-regional disease. With a median followup of 29 months, survival was significantly better (p less than .01) in patients receiving CTI to the chest after complete response to CAV (both limited disease and extensive disease) than without CTI. Of 41 patients completing the protocol and without central nervous system (CNS) involvement at presentation, four (9%) failed initially in the CNS (two brain, two spinal axis); CNS failure was the cause of death in all four patients with no other sites of metastases at death in two of these. Failure to complete protocol treatment was due to disease progression during chemotherapy in 25/73 (34%) and chemotherapy related complications (three sepsis, one gastrointestinal bleed) in four of 73 (5.5%) patients. CTI and prophylactic neuraxis irradiation did not increase morbidity or result in mortality in the sequence utilized; prophylactic neuraxis irradiation appears to reduce the CNS relapse rate, and CTI benefits survival.

Actuarial Analysis↗
PubMed1985

What is the lowest effective biologic dose for prophylactic cranial irradiation?

Between January 1974 and September 1984, 327 consecutive patients with small cell carcinoma of the lung (SCCL) free of clinical and brain scan (radionuclide or computed tomography) evidence of brain metastasis were treated at the Medical College of Wisconsin Affiliated Hospitals. All patients received single agent chemotherapy, consisting of cyclophosphamide or methotrexate (1974-1975), or combination chemotherapy with cyclophosphamide, doxorubicin, and vincristine with or without methotrexate and leukovorin (1976-1984). Between January 1974 and December 1974, 82 patients were treated with chemotherapy without prophylactic cranial irradiation (PCI). Between 1978 and 1984, all patients received PCI during the first week after diagnosis, simultaneous with their first cycle of chemotherapy. Chest irradiation was given to the complete responders to the chemotherapy. During the first 31/3 years of the study with PCI (January 1978-May 1981), 51 patients received 30 Gray (Gy) in 10 fractions in 2 weeks and five of them (10%) developed brain metastasis. Thereafter, 25 Gy in 10 fractions was consistently administered for PCI. Six of 194 patients (3%) developed brain metastasis. The cumulative (time corrected) probability of brain metastasis was approximately 10% at 1 year and was similar for patients who received 25 Gy and those who received 30 Gy. Although detailed neuropsychological testing has not been performed, clinically apparent late sequelae that might be attributed to PCI have not been seen. Nonetheless, the dose fractionation regimen of 25 Gy in 10 fractions with combination chemotherapy, cyclophosphamide, doxorubicin (or methotrexate), and vincristine is as effective in eliminating subclinical metastasis to the brain. It can be recommended for future trials until more data become available about late sequelae of treatment of SCCL and the patient characteristics and treatment factors that may contribute.

Actuarial Analysis↗
PubMed1985

Concurrent myelodysplasia and lymphoproliferation: a disorder of the true pluripotential stem cell?

The lymphoproliferative disorders and the myelodysplastic syndromes are thought to result from the clonal expansion of a single abnormal precursor cell. Seven patients who were found to have concurrent myelodysplasia and lymphoproliferation are described. In all cases myelodysplasia and lymphoproliferation were diagnosed simultaneously or myelodysplasia preceded overt lymphoproliferation by a brief interval. Thus, myelodysplasia in these patients was not related to treatment given for a lymphoproliferative disorder. Stem cell theory is reviewed with special reference to evidence for an adult human stem cell common to both haemopoietic and lymphoid cell lines (CFU-L-M). The presence of concurrent myelodysplasia and lymphoproliferation in these seven patients may be the result of the clonal expansion of an abnormal pluripotential stem cell. It may be possible in some cases to achieve remission of the lymphoproliferative disorder with return of normal haematopoiesis if residual normal stem cells are present and repopulate the marrow following cytotoxic therapy.

Adult↗
PubMed1984

Late-onset, warfarin-caused necrosis occurring in a patient with infectious mononucleosis.

A 25-year-old man with Klinefelter's syndrome and recurrent thromboplebitis , for which he had been receiving long-term warfarin sodium therapy, had bilateral ecchymoses on the hips coincident with serologically confirmed Epstein-Barr virus-caused mononucleosis. Biopsy specimens taken from the hip lesions showed microscopic findings consistent with a diagnosis of warfarin necrosis. Direct immunofluorescence microscopy disclosed vessel-wall deposition of IgM and heavy upper-dermal deposition of IgG. Electron microscopy disclosed nonspecific endothelial cell blebs that projected into the vessel lumen. The temporal association of mononucleosis with the onset of warfarin necrosis suggests that the viral illness may have precipitated an immunologic endothelial surface reaction, leading to thrombosis and secondary hemorrhage with infarction. To our knowledge, the appearance of warfarin necrosis in a patient receiving long-term, stable anticoagulation therapy has not been previously reported.

Adult↗