Fludarabine and acute tumor lysis in chronic lymphocytic leukemia.
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Biomedical subjects
Publications and source records attributed to J N Frame.
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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-kappa paraprotein who had development of an eruption of pruritic papules and demonstrated the following unusual immunopathologic findings: (1) deposits of IgM-kappa in the epidermal basement membrane zone of lesional and nonlesional skin; (2) a circulating IgM-kappa antiepidermal basement membrane zone antibody; and (3) binding of this circulating IgM-kappa 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.
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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, EAET rosetting, 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): SBA+B (99.9%), SBA+EAET (99.8%), CP1+C' (99.4%), anti-T cell ricin A chain immunotoxin (99.0%), and SBA alone (94.2%). Neither PHA response nor enumeration of residual EAET rosettes 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 CP1+C', XomaZyme-H65, and SBA plus sheep erythrocyte 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%.
Quantitations of residual T cells by limiting dilution analysis (LDA), immunofluorescence analysis, sheep red cell rosetting, and proliferative responses to phytohemagglutinin were done to identify treatment conditions that maximized the ex vivo T cell depletion (TCD) of human bone marrow (BM) with the rat monoclonal antibody Campath-1 (CP1) and complement (C'). Different treatment approaches achieved levels of TCD varying from 0.4 to 2.6 log10. However, under optimal treatment conditions, a mean (+/- SEM) log10 TCD of 2.60 +/- 0.12 was demonstrated by LDA. Concentrations of CP1 ranging from 5 micrograms to 300 micrograms/10(7) cells/ml achieved equally effective TCD as determined by LDA. An inverse relationship between the concentration of BM cells/ml and the extent of TCD was observed. Additional C' treatment did not increase TCD as detectable by LDA. Mean recoveries of CFU-GM (day 7), CFU-GM (day 14), CFU-GEMM, and BFU-E growth following CP1 + C' were 51, 43, 42, and 45% respectively. These results demonstrate the importance of cell concentration and treatment conditions for maximizing the depletion of BM T cells with CP1 + C'.