PubMed Health⌕ Search

Biomedical subjects

M H Zakem

Publications and source records attributed to M H Zakem.

4 recordsLinked to original sources

Low level CD20 expression on T cell malignancies.

Although initially thought to be a B lineage restricted antigen, low "density" or antibody binding capacity (ABC) CD20 has recently been detected on subset(s) of normal T lymphocytes (Hultin et al.: Cytometry 14:196-204, 1993). We report low ABC CD20 expression in three (two children, one adult) cases of T-acute lymphoblastic leukemia (T-ALL). CD20 and other pertinent antigens were detected using a direct dual color method with a Becton Dickinson FACScan flow cytometer and Simulset software. Only one cell population based on light scatter was noted in each case that immunophenotypically represented almost a pure population of malignant cells expressing T lymphocyte antigens (for example, CD7 98%, 92%, and 100%, respectively). A total of 95%, 87%, and 79% of the cells from the three cases expressed CD20 with an unusual low ABC compared to the customary "bright" CD20 expression on normal B lymphocytes. Other B lymphocyte associated antigens, such as CD19, CD22, Dr, and immunoglobulin light chains, were negative. Eleven other T lymphocytic malignancies from 1991 to 1993 were CD20 negative, including three other case of T-ALL (one adult and two children). One unusual case of intestinal small lymphocytic non-Hodgkin's lymphoma with a natural killer/T lymphocytic immunophenotype not described in this report appeared to be CD20"dim"+. Low ABC CD20 expression by T lymphocytic malignancies may provide a more unique immunophenotypic "fingerprint" to help support the diagnosis of T cell neoplasia vs. normal/reactive T cells (for example, low ABC CD20 cells represent only 2.4 +/- 1.5% of normal peripheral blood lymphocytes). This characteristic might also facilitate monitoring patients for residual or recurrent disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: a pilot study.

Thirty-one evaluable patients with measurable advanced colorectal carcinoma were entered into a pilot study that used weekly fluorouracil (5-FU) at the dose of 600 mg/m2 by bolus infusion administered midway during a two-hour leucovorin calcium infusion of 500 mg/m2. This regimen was repeated weekly for six doses. Twenty-seven of these patients (87%) were considered to be refractory to prior 5-FU therapy and four (13%) were previously untreated. All 31 patients successfully completed at least one 6-week cycle of this regimen with acceptable toxicity. The combined complete (CR) and partial response (PR) rate was 45% with another 25% of patients remaining stable. The 95% confidence levels for the responding patients are 27.6% and 62.7%, respectively. The remaining 30% of the patients had all received prior 5-FU therapy and progressed. All of the responding patients and 80% of the patients with stable disease received two or more cycles of this regimen after a 3- to 4-week interval off therapy. The median time to disease progression was 16.1 months for responding patients and 6.7 months for those patients with stable disease. The median survival for the responders was 20.6 months and for those with stable disease 9.8 months. The median survival for the nonresponding patients was 3.9 months. Toxicity included diarrhea in 70% of patients, skin rash (erythema) in 10%, stomatitis in 15%, nausea and vomiting in 25%, and myelosuppression in 10%. This study confirms and extends previous observations that demonstrate the improved efficacy of 5-FU when used with high-dose leucovorin in advanced colorectal carcinoma.

Adenocarcinoma↗

Bioavailability of high-dose oral leucovorin.

Fifteen adult subjects comprised the study group; 2 were colon cancer patients. Total leucovorin (citrovorum factor; CF) doses of 200, 400, 800, and 1600 mg were equally subdivided and administered at 0, 1, 2, and 3 hours. Three of the subjects were fasting and the other 12 were not. Quantitation of serum L-CF by Pediococcus cerevisiae and total reduced folates (TRF) by radio-assay were performed in 10 samples from each subject drawn over a 12-hour period after initiation of CF dosing. The mean serum levels of L-CF remained greater than 0.1 microM at 3 hours and the TRF 3.5 microM at 5 hours, respectively, after termination of CF dosing in all subjects treated at the 800- and 1600-mg dose schedule. At all CF dosage schedules employed, peak serum concentrations were reached within 4 and 6 hours after initiation of oral CF. Peak TRF concentrations at the 200-, 400-, 800-, and 1600-mg doses were 3.42 +/- 0.65, 4.05 +/- 1.04, 4.81 +/- 0.14, and 5.11 +/- 1.81 microM, respectively. Peak L-CF levels at 200, 400, 800, and 1600 were 0.15 +/- 0.11, 0.21 +/- 0.14, 0.23 +/- 0.11, and 0.34 +/- 0.16 microM. Based upon these observations, the following conclusions were reached: 1) no significant differences were observed in serum concentrations of folates between the 800- and 1600-mg dose schedules; 2) at these doses serum concentrations of L-CF and TRF were achieved that warrant a phase I investigation of high-dose oral CF with standard dose FUra in patients with advanced colorectal carcinoma.

Administration, Oral↗

Treatment of advanced stage mycosis fungoides with bleomycin, doxorubicin, and methotrexate with topical nitrogen mustard (BAM-M).

Ten patients with advanced stage (TNM IIB-IVB) mycosis fungoides were treated with a combination chemotherapy program consisting of bleomycin and methotrexate weekly, doxorubicin every 3 weeks, and topical nitrogen mustard daily (BAM-M). Seven patients obtained histologically documented complete remissions ranging from 4 to 105+ months in duration. Median survival is 16.5+ months. Three patients in whom splenomegaly was detected during their staging evaluation underwent splenectomy. These three patients have had unmaintained disease-free survivals of 36+, 100+, and 105+ months. This study indicates that BAM-M is effective therapy for advanced stage mycosis fungoides and suggests that the therapeutic role of splenectomy should be evaluated further.

Adult↗