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Biomedical subjects

B Jegasothy

Publications and source records attributed to B Jegasothy.

13 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↗
PubMed1994

Proliferation cell nuclear antigen and soluble interleukin 2 receptor levels in cutaneous T cell lymphoma: correlation with advanced clinical diseases.

Cutaneous T-cell lymphoma and leukemias (CTCL) are malignant clonal proliferation of T lymphocytes which have a predilection to home to and proliferate in skin. There are no clinical and laboratory parameters which consistently correlate with stage of disease, which varies from patch, plaque, tumor, or erythroderma. Soluble IL-2 receptor (sIL2-R) levels are elevated both in benign and malignant diseases involving immune activation. Proliferation cell nuclear antigen (PCNA) is a marker of the G1 and G/S phases of cell cycle and can be used to quantitate proliferation. We studied 43 skin biopsies of CTCL in various clinical stages for the presence of PCNA via immunoperoxidase techniques to establish a relationship between PCNA and the stage of disease. In addition, sIL2-R levels were determined in 14 patients. PCNA reactivity was detected in the nuclei of infiltrating cells in a total of 25 patients (58%). According to clinical stage there were 2/12 patch (12%), 9/17 plaque (53%), 4/4 tumor (100%) and 9/10 erythrodermic (90%) stage patients with PCNA positive cells. Thus PCNA positivity correlated with advanced clinical stage. sIL2-R levels were elevated in 14 of 14 patients and the degree of elevation correlated with advanced clinical stage of disease and with increased numbers of PCNA positive cells. Immunohistochemical studies for PCNA and serum sIL2-R levels can be used as laboratory parameters to correlate with clinical stage of disease and enhance prognostication in CTCL.

Humans↗
PubMed1992

Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy.

BACKGROUND: This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease. OBJECTIVE: Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls. METHODS: Files of patients from the original photopheresis study centers were reviewed and their current status was documented. RESULTS: The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy. CONCLUSION: Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.

CD4-CD8 Ratio↗
PubMed1990

Anti-V region antibodies as "almost clonotypic" reagents for the study of cutaneous T cell lymphomas and leukemias.

Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an "almost clonotypic" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL.

Antibodies, Monoclonal↗
PubMed1990

Establishment of a human cutaneous T-cell lymphoma in C.B-17 SCID mice.

Investigation into the immunobiology of cutaneous T-cell lymphomas (CTCL) would be facilitated by the development of a suitable experimental system. The recent use of mice with severe combined immune deficiency (SCID) as a vehicle to study the human immune system prompted us to try to establish CTCL in SCID mice. We found that a CD4+ lymphocytic infiltrate characteristic of CTCL was maintained within patient skin grafts in place on natural killer cell depleted SCID mice for the month of observation. CTCL cells were not found outside the human skin graft. This chimeric model using SCID mice and patient lesional skin should provide a useful tool to characterize CTCL/skin microenvironmental interactions and to test new therapeutic approaches.

Animals↗
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

Clobetasol propionate versus fluocinonide creams in psoriasis and eczema.

A double-blind, parallel comparison was made of the short-term efficacy and safety of three times daily regimens of 0.05% clobetasol propionate cream and 0.05% fluocinonide cream in 114 adolescent and adult patients with psoriasis and 113 with eczema. After 2 weeks of topical applications, patients were assessed according to (1) investigators' overall judgment of clinical response, (2) degree of severity of specific signs and symptoms, and (3) patients' evaluation of improvement. In all three response categories in psoriasis, and in two of three in eczema, clobetasol was statistically significantly superior to fluocinonide (p less than 0.05-p less than 0.001). Healing commenced more rapidly with clobetasol and there was no indication of tachyphylaxis. In contrast, the healing rate with fluocinonide slowed noticeably after the first week, and there was a greater tendency to relapse following fluocinonide treatment. Both regimens were safe: drug-related side effects were generally mild and occurred most commonly with fluocinonide therapy in eczema patients. Overall, drug-related effects occurred in 4% of patients receiving clobetasol and 12% receiving fluocinonide (p less than 0.05). Transient morning plasma cortisol reductions below 5 micrograms/dl occurred in 6% of clobetasol-treated patients, reverting to normal within 1 week of the end of treatment.

Administration, Topical↗
PubMed1984

The sign of Leser-Trélat associated with primary lymphoma of the brain.

The sign of Leser-Trélat has been defined as the sudden appearance of seborrheic keratoses in number and/or size in association with an underlying malignancy. There have been only thirty-two reported cases of the sign of Leser-Trélat since it was first described in 1984. This is the first known case of primary lymphoma of the brain associated with this sign. Until Dantzig's review of the literature in 1973, the only tumor type associated with this sign had been adenocarcinomas of the gastrointestinal tract and the genitourinary tract. Since that time there have been only nine cases reported that were not adenocarcinomas; of those, only four cases have been lymphoproliferative malignancies. We wish to emphasize the need for further reports of this sign to better characterize it and to make physicians more aware of the association between this dermatologic sign and an internal malignancy.

Aged↗
PubMed1983

Lymphocyte abnormalities in the BB rat.

The BB rat has a marked T cell lymphocytopenia, with a near absence of peripheral "helper" T cells recognized by monoclonal antibody W3/25 (W3/25+ T cells). The lymphocytes of the BB rat's spleen and thymus were examined for the presence of W3/25+ T cells, which were found to be absent in the spleen but present in normal amounts in the thymus. Concanavalin A (Con A) responsiveness was absent in the BB's peripheral blood and spleen but present in the thymus. Thus, in these three lymphoid compartments, Con A responsiveness directly correlated with the presence or absence of W3/25+ T cells. These lymphocyte abnormalities in the BB rat are notably different from lymphocyte changes present in human type I diabetes.

Animals↗
PubMed1979

Preliminary evaluation of 15 chemotherapeutic agents applied topically in the treatment of mycosis fungoides.

This is an interim report of a double-blind multi-institutional study to examine the effect of chemotherapeutic agents applied topically to patients with mycosis fungoides. To date, 41 patch tests have been completed using 15 drugs. Five of the drugs produced some improvement, four were highly irritating, and six had no effect. This patch-testing study is a prelude to more extensive therapy trials.

Administration, Topical↗