Search

PURPOSE: A common germline mutation in the factor V gene ([FV:Q.sup.506]) has been associated with hypercoagulability in families with heritable predisposition to thrombosis. We examined the prevalence and clinical significance of the [FV:Q.sup.506] mutation in cancer patients. PATIENTS AND METHODS: We performed a retrospective cohort study by examining 353 consecutive, unselected patients in a general hematology/oncology clinic. We ascertained risk factors, obtained the clinical clotting history, and determined the heterozygous or homozygous presence of the [FV:Q.sup.506] allele for each patient. RESULTS: We detected a germline mutation in 5.4% (19 of 353) of patients, of whom 18 were heterozygous and l was homozygous for the [FV.Q.sup.506] mutant allele. In 17 of 18 heterozygous patients, there was no history of venous thrombosis or catheter-associated thrombosis. These asymptomatic patients included 13 patients who had been diagnosed with cancer or leukemia for a mean of 66.2 months (median 69) and had received a variety of local and systemic treatments. in contrast, 1 of 18 heterozygous and 1 of 1 homozygous patients had developed deep vein thrombosis that was associated, respectively, with either recurrent thrombotic events or a strong family history for pulmonary embolus. CONCLUSIONS: Routine screening for the [FV:Q.sup.506] mutation in cancer patients without a personal or family history for venous thrombosis is not helpful in guiding management. in contrast, an episode of venous thrombosis in a patient with a mutant germline [FV:Q.sup.506] allele was associated with recurrent thrombotic events. These findings suggest that patients heterozygous for the [FV:Q.sup.605] allele may require an independent 'susceptibility' element to manifest a venous hypercoagulable state. in addition, only 2 of a clinic patients with a venous clot carried the [FV:Q.sup.506] allele suggesting this genetic defect plays a minor role in the hypercoagulable state of cancer. Am J Med. 1996;101:406-412.

Objective: Design of a cost-effective algorithm for staging disease in patients with small-cell lung cancer. Design: An algorithm was constructed by analyzing all permutations of a sequence of procedures required to stage disease in patients with small-cell lung cancer. Procedural costs were determined, and the model was applied to the small-cell lung cancer patient population treated at the National Cancer Institute, Bethesda, Md, from 1973 to 1989. The final algorithm was derived from the permutation with the lowest cost per accurately staged patient. Setting: A single government institute, the National Cancer Institute. Patients: Four hundred fifty-one patients with previously untreated, consecutive histologically documented small-cell lung cancer entered into therapeutic protocols at the National Cancer Institute from April 1973 through July 1989. Data were obtained from small-cell lung cancer protocol databases and patients' medical records. Main Outcome Measure: The cost per patient of each sequence of staging procedures when applied to the patient population. Results: The least expensive sequence of procedures saved $1418 per patient when compared with application of a standard set of staging procedures to all patients. The major factor in reducing costs was the concept of stopping the staging procedures after a site of distant metastatic disease had been identified. Conclusions: An algorithm consisting of a set of sequential staging procedures can accurately stage disease in patients with small-cell lung cancer and save more than one third of the costs of an inclusive standard set of staging procedures. (Arch Intern Med. 1993;153:329-337)

The aim of this study was to compare the extent of in vitro T cell depletion and recovery of hematopoietic progenitor cells achieved with five methods of T cell depletion. Bone marrow samples from the same source were treated with monoclonal antibody Campath-1 (CP1) and human complement, XomaZyme-H65 (anti-T cell ricin A chain immunotoxin), or soybean agglutinin (SBA) alone or in combination with sheep erythrocytes (EAET) or a cocktail of immunomagnetic beads (B) directly coated with anti-CD2, anti-CD3, or anti-CD8 monoclonal antibodies. Residual T cells were enumerated by limiting dilution analysis, EAETrosetting, and proliferative responses to phytohemagglutinin. The results of this study demonstrated the following reductions in BM T cells as detected by limiting dilution analysis (mean control): SBAB (99.9), SBAEAET(99.8), CP1C' (99.4), anti—T cell ricin A chain immunotoxin (99.0), and SBA alone (94.2). Neither PHA response nor enumeration of residual EAETrosettes provided discriminating differences in the degree of T cell depletion by treatment method when T cell reductions exceeded 99.0 by LDA. These results demonstrate the ability of CP1C', XomaZyme-H65, and SBA plus sheep eryth-rocyte or magnetic bead depletion to achieve a greater than 99 reduction of BM T cells and the importance of limiting dilution analysis in defining differences in T cell numbers when depletion exceeded 99.

• BACKGROUND.— Waldenström macroglobulinemia, a lymphoplasmacytoid cell malignant neoplasm associated with a monoclonal IgM paraprotein, has been associated with a number of cutaneous manifestations. On rare occasions, IgM deposits have been demonstrated in the epidermal basement zone of patients with WM. OBSERVATIONS.— We report the case of a patient with Waldenström macroglobulinemia and IgM-κ paraprotein who had development of an eruption of pruritic papules and demonstrated the following unusual immunopathologic findings: (1) deposits of IgM-κ in the epidermal basement membrane zone of lesional and nonlesional skin; (2) a circulating IgM-κ antiepidermal basement membrane zone antibody; and (3) binding of this circulating IgM-κ antiepidermal basement membrane zone antibody to both sides of 1 mol/L sodium chloride split skin. The cutaneous eruption cleared completely with oral psoralen with long-wave UV radiation in the A range (PUVA) therapy. CONCLUSIONS.— We present a patient with Waldenström macroglobulinemia who had a distinctive papular eruption and immunopathologic findings suggesting that his paraprotein has specificity for the epidermal basement membrane zone.(Arch Dermatol. 1992;128:372-376)