Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma

PURPOSE: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 ((131)I). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of (131)I-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed. MATERIALS AND METHODS: Twenty patients with advanced NHL entered the study a total of 21 times. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. (131)I-Lym-1 was given after Lym-1 and (131)I was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m2 body surface area. RESULTS: Mean radiation dose to the bone marrow from body and blood (131)I was 0.34 (range, 0. 1 6 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/ MBq). Dose-limiting toxicity was grade 3 to 4 thrombocytopenia with an MTD of 100 mCi/m2 (3.7 GBq/m2) for each of the first two doses of (131)I-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71 %) of 14 entries who received at least two doses of (131)I-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m2) cohort had complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of (131)I-Lym-1. CONCLUSION: (131)I-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of (131)I-Lym-1 was 100 mCi/m2 (total, 200 mCi/m2) (3.7 GBq/m2; total, 7.4 GBq/m2).     

Choices: biomedical ethics and women''s health. Ethical issues and dilemmas

Distribution of markers of local cell-mediated immunity was examined in oral tumors exhibiting different histological stages of differentiation. Using a RT-PCR-based semiquantitative technique we determined levels of Langerhans cells, CD4- and CD8-positive T-cells, macrophages/NK cells, beta2-microglobulin and IFN-gamma mRNAs from tissue biopsies. A positive correlation was found between levels of these immunological markers and the tumor differentiation stage. Since tumor differentiation may correlate with the prognosis and response to various treatment modalities, our results may be useful clinically.     

Human Mig chemokine: biochemical and functional characterization

Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine-activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+]i in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full-length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells.     

The value of palpation as basis for decision on lymph node excision

The purpose of the study was to evaluate palpation of the regional lymph nodes in control examinations of patients with malignant disease. A retrospective review of the medical records of 188 cases in which the patients had had an extirpation of the regional lymph nodes was performed. We have compared the preoperative findings through palpation with the histological diagnosis. The patients were grouped according to the region in which the lymph node removal had been done. The specificity of palpation when the histological diagnosis was malignant was (with 95% confidence limits), in the axilla 0.65 (0.54-0.75), in the inguinal region 0.86 (0.75-0.94) on the neck 0.83 (0.52-0.98) and in the suprahyoid region 0.58 (0.28-0.85). In conclusion, palpation of regional lymph nodes is not a sufficient control examination in the estimation of the course of malignant disease. Supplementary examination methods are recommended.     

Diagnosis and management of colovesical fistulas

Diagnosis and management may present difficult problems in patients with colovesical fistulas. Symptoms in the urinary tract are most common, and cystoscopy, and cystography are the most valuable diagnostic procedures. It may not always be possible to demonstrate the fistula by diagnostic tests, and a high index of suspicion should be maintained in patients with inflammatory or neoplastic disease of the rectosigmoid area or bladder with recurrent cystitis. Definitive treatment should include resection of the fistula and diseased segment of the intestine. Both one stage and multistage procedures have their place in the treatment of this condition. There are specific criteria for success for a one stage procedure.