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E Vonderheid

Publications and source records attributed to E Vonderheid.

11 recordsLinked to original sources
PubMed2001

Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Adult↗
PubMed2000

Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter.

SHP-1 is an important negative regulator of signaling by several receptors including receptors for interleukin-2 (IL-2R) and other cytokines. SHP-1 acts by dephosphorylating the receptors and receptor-associated kinases such as IL-2R-associated Jak3 kinase. We found that SHP-1 protein was not detectable or greatly diminished in most (six of seven) T cell lines derived from various types of T cell lymphomas and all (eight of eight) cutaneous T-cell lymphoma tissues with a transformed, large-cell morphology. All T-cell lymphoma lines tested (eight of eight) expressed diminished amounts or no detectable SHP-1 mRNA. These T cell lines did not, however, carry any mutations in the SHP-1 gene-coding, splice-junction, and promoter regions. Importantly, SHP-1 DNA promoter region in the T cell lines was resistant to digestion with three different methylation-sensitive restriction enzymes. This resistance was reversed by treatment of the cells with a demethylating agent, 5-deoxyazacytidine. The treatment resulted also in the expression of SHP-1 mRNA and, less frequently, SHP-1 protein. The expression of SHP-1 protein was associated with dephosphorylation of the Jak3 kinase. These results show that lack of SHP-1 expression is frequent in malignant T cells and results from methylation of the SHP-1 gene promoter. Furthermore, they indicate that SHP-1 loss may play a role in the pathogenesis of T cell lymphomas by permitting persistence of signals generated by IL-2R and, possibly, other receptor complexes.

Azacitidine↗
PubMed1987

Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results.

Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.

Administration, Oral↗
PubMed1985

Granular cell tumor: a great masquerader.

Granular cell tumor usually presents as an asymptomatic mass in the skin or subcutaneous tissue, yet it is rarely considered in the clinician's differential diagnosis of such masses. We present a case of granular cell tumor located on an extremity and discuss its characteristic histopathologic findings and aspects of its origin and management.

Adult↗
PubMed1985

Lymphomatoid papulosis. A cutaneous proliferation of activated helper T cells expressing Hodgkin's disease-associated antigens.

A distinctive immunologic phenotype was demonstrated for the characteristic large atypical cells in skin lesions of 9 patients with lymphomatoid papulosis (LP). Coexpression of Hodgkin's disease (HD)-associated antigen(s) Ki-1, and often Leu-M1, with helper T-cell antigens T11, T4, and T3 and cellular activation antigens Tac, Ia, and T9 was the most common phenotype, observed in 6 of 9 cases. In 2 cases T-cell-specific antigens were not detected, and the phenotype was indistinguishable from Reed-Sternberg (RS) cells of HD. Numerous Ki-1 positive cells and infrequent expression of Leu-1 antigen by large atypical cells in LP cases facilitated the differential diagnosis between LP and mycosis fungoides. A possible transition between small, medium, and large cells expressing only T-cell antigens and large transformed RS-like cells expressing both T-cell and HD-associated antigens was shown by immunoelectron microscopy. These immunologic findings should prove useful for the diagnosis of LP and may help to explain the unexpectedly frequent clinical associations of LP, mycosis fungoides, and HD.

Antigens, Neoplasm↗
PubMed1985

Immunopathology of cutaneous T-cell lymphomas.

In this study the authors attempted to establish immunopathologic criteria for the distinction of various T-cell lymphomas affecting the skin. We studied skin specimens from 27 patients with mycosis fungoides (MF) (n = 12), the Sézary syndrome (SS) (n = 6), adult T-cell leukemia (ATL) (n = 4), and nonepidermotropic T-cell lymphoma of large cell (n = 4) and lymphoblastic (n = 1) types. Identification of tumor cells in mixed cell populations and detection of weak expression of surface antigens by tumor cells was facilitated by immunoelectron microscopy. The mature helper T-cell phenotype (T11+ T3+ T4+) was found in 14 of 18 cases of MF/SS. One case of MF had a cytotoxic/suppressor (T4- T8+ 3A1+) phenotype; one with frequent blastic cells showed only weak expression of T4 antigen; 2 cases of SS were T11-. Tumor cells infiltrating the skin expressed 3Al antigen in 44% and cellular activation antigens Ia and/or Tac in 78% of patients with MF/SS. No consistent phenotypic differences were found between ATL cells from ATLV (HTLV) antibody-positive patients and tumor cells of patients with MF/SS who lacked this antibody. In contrast, a group of nonepidermotropic T-cell lymphomas showed phenotypic differences from MF/SS and ATL in all but 1 case. These cases were distinguished by the frequent absence of T3, T4, and Leu 1 antigens in 3 large-cell lymphomas; frequent expression of Ki-1 antigen, a Hodgkin's disease-associated antigen, in 2 cases with RS-like cells; and an immature thymocyte phenotype in lymphoblastic lymphoma. These findings demonstrate that tumor-cell phenotypes can be useful in distinguishing different histologic types of cutaneous T-cell lymphoma.

Adult↗
PubMed1984

In situ study of T-cell subpopulations in cutaneous T-cell lymphoma. Diagnostic criteria.

The T-cell subpopulations present in skin biopsy specimens from 91 patients with cutaneous T-cell lymphoma (CTCL) and from 19 patients with benign lymphocytic infiltrates of the skin were examined in situ to define criteria for the differentiation of benign from malignant lymphocytic infiltrates. The monoclonal antibodies OKT 1 (pan T-cell), BE 3 (pan T-cell), OKT 4 (helper/inducer T-cell), OKT 6 (cortical thymocyte and Langerhans' cell), OKT 8 (suppressor T-cell), and OKT 10 (pan thymocyte) were used in direct or indirect immunoperoxidase reactions. Sections were examined at high magnification, and the distribution and percentage of cells reactive with each antibody were assessed. Three main patterns of staining were observed in the CTCL patients: (1) 64% of the biopsy specimens showed that 60% of the cells present in the dermis were T-cells that were OKT 1+ and BE 3+ and there was an even distribution of the different T-cell subpopulations, with 54% being OKT 4+ and 8% OKT 8+; (2) 21% patients showed selective loss of OKT 1 antigen, and 80% of these also showed loss of BE 3 antigen; and (3) 15% patients showed large numbers of OKT 8+ cells (range, 50%-90%) but the percentages of OKT 1+ and OKT 4+ cells were within the ranges seen in Group 1, indicating the presence of a population of T-cells simultaneously expressing OKT 4 (helper/inducer) and OKT 8 (suppressor) reactivity. In 95% of the CTCL patients, 3.5% OKT 6+ cells were present in the dermal infiltrate, and in 92% of patients, 3% OKT 10+ cells were present. Comparing sections from CTCL and benign dermatoses, no single diagnostic feature was identified, but helpful differentiating features were: (1) the even, rather than nodular, distribution of the T-cell subpopulation; (2) the selective loss of OKT 1 and BE 3 antigens; (3) the presence of T-cells simultaneously expressing OKT 4 and OKT 8 antigens; and (4) the presence of OKT 10+ cells.

Antibodies, Monoclonal↗
PubMed1980

Reversible (G0) and nonreadily reversible (Q) noncycling cells in human peripheral blood. Immunological, structural, and biological characterization.

PHA-stimulated human lymphocytes (normal-resting-proliferating) at 0, 24, 48, 72, and 144 h were studied with Acridine Orange (AO) staining. By viable cell sorting, by subsequent subculturing, and by the use of biochemical, biophysical, and immunological assays, not only have the G0 resting and G1 (cycling) cell cycle phases been objectively characterized, but a separate subpopulation of quiescent cells that are functionally viable and deeply committed to nonproliferation, the Q cells, has been identified. Multiparameter cytofluorimetric analysis, methyl14C-thymidine incorporation, automated image analysis, and mitogen stimulation studies have shown that the "Q" cell, compared to the "G0" resting but easily recruitable cell, exhibits quite lower red and green AO emission, possesses 2c to 4c DNA content (rather than only 2c), has a higher average optical density, and is either nonrecruitable or recruitable-with-difficulty in PHA-stimulated lymphocyte cultures.

Acridine Orange↗
PubMed1978

Lymphocyte transformation in patients with staged mycosis fungoides and Sézary syndrome.

Lymphocyte transformation was studied in patients with mycosis fungoides and the Sézary syndrome with particular reference to the stage of disease. Phytohemagglutinin-induced lymphocyte blastogenesis was normal in stage II, became depressed in stage III and was greatly reduced in stage IV disease. Similar abnormalities were found in patients with the Sézary syndrome once the proportion of abnormal cells in the peripheral blood exceeded 10%. It is concluded that stag III mycosis fungoides is probably a critical period in determining dissemination of the disease.

Adult↗