High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma.

Allogeneic stem cell transplantation (SCT) has been shown to be a curative therapy for some patients with non-Hodgkin's lymphoma (NHL). Total-body irradiation and high-dose cyclophosphamide combinations are the most established conditioning regimens used in this setting. We examined the efficacy and toxicity of cyclophosphamide, BCNU, and VP-16 (CBV) as a suitable chemotherapy-only regimen for NHL patients. In total, 18 patients, median age 42 years, with NHL were treated with CBV followed by allotransplant. Patients had received a median of two prior chemotherapy regimens. Median times to neutrophil and platelet recovery were 19 and 15 days, respectively. Interstitial pneumonitis occurred in one patient. There have been four relapses after a median follow-up of 39 months. Overall, there were four deaths, one because of relapse. The 2-year estimates of relapse-free and overall survival are 56 and 76%, respectively. CBV is a safe and an effective alternative to TBI-containing regimens before allogeneic SCT for NHL.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome.

Patients with advanced MDS and secondary AML respond poorly to chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate proliferation of leukemic blasts and sensitize these cells to the cytotoxic effects of S-phase-specific drugs. This is the first report of safety and efficacy of GM-CSF prior to and during cytarabine in a low-dose, intermittent regimen for elderly patients with poor risk acute myelogenous leukemia or myelodysplastic syndrome. Twenty patients, age 68 to 86 years, each received 250 microg/m2 of GM-CSF (Sargramostatin; Immunex, Seattle, WA, USA) subcutaneously (s.c.) or intravenously (i.v.) for 3 days followed by GM-CSF at the same dose and cytarabine 100 mg/m2 i.v. for 3 days. GM-CSF and cytarabine were both administered for 3 days during weeks 2 and 3 followed by a 3-week rest period. Rates of CR and PR were 20% and 40%, respectively. These included clinically significant resolution of cytopenias and transfusion requirements. Many of the responding patients had been heavily pretreated prior to enrollment. One- and 2-year survival estimates are 44% and 19%, respectively. Myelosuppression was the most significant toxicity. Our findings suggest that this novel combination of GM-CSF with sequential and concomitant low-dose cytarabine can benefit patients with poor risk myeloid malignancies.

Inactivated whole-cell bacterial vaccines: current status and novel strategies.

Inactivated bacterial whole-cell vaccines have been the most widely studied prophylactic treatment for infectious diseases. They offer an economical, and potentially safe, effective means of preventing disease. The disadvantages of these vaccines have been that parenteral administration, while effective in some instances, may have caused adverse reactions in vaccinees, while oral administration often required high doses and resulted in short-term immunity. More recent studies describing new approaches for improving antigenicity of inactivated whole-cell vaccines and the enhancement of immune responses to oral immunization offer great hope for improving the efficacy of these agents. Promising whole cell vaccines include those against Vibrio cholerae, enterotoxigenic Escherichia coli, and more recently Campylobacter jejuni.

Effect of bile on Vibrio parahaemolyticus.

Many enteric pathogens are thought to enter a viable but nonculturable state when deprived of nutrients. Virulent strains of the enteric pathogen Vibrio parahaemolyticus are rarely isolated from their low-nutrient aquatic environments, possibly due to their nonculturability. Host factors such as bile may trigger release from dormancy and increase virulence in these strains. In this study, the addition of bile or the bile acid deoxycholic acid to estuarine water-cultured bacteria led to an increase in the direct viable count and colony counts among the virulent strains. This effect was not demonstrated in the nonvirulent strains, and it was reversed by extraction of bile acids with cholestyramine. Bile-treated V. parahaemolyticus had lower levels of intracellular calcium than untreated cells, and this effect coincided with an increase in the number of metabolically active cells. Chelation of intracellular calcium with BAPTA/AM (R. Y. Tsien, Biochemistry 19:2396-2402, 1980) produced similar results. Addition of bile to V. parahaemolyticus cultures in laboratory medium enhanced factors associated with virulence such as Congo red binding, bacterial capsule size, and adherence to epithelial cells. These results suggest that a bile acid-containing environment such as that found in the human host favors growth of virulent strains of V. parahaemolyticus and that bile acids enhance the expression of virulence factors. These effects seem to be mediated by a decrease in intracellular calcium.

Isolation and characterization of oat globulin messenger RNA.

When polyadenylated RNA, isolated from membrane-bound polysomes extracted from developing oat (Avena sativa L.) seeds, was translated in vitro in the rabbit reticulocyte system, two polypeptides of about 58 and 60 kilodaltons were immunoprecipitated by anti-oat globulin antibody. No electrophoretic bands corresponding to the 40 and 20 kilodalton polypeptides of oat globulin were present. However, when in vivo labeled extracts were immunoprecipitated with anti-oat globulin antibody, three groups of polypeptides (60, 40, and 20 kilodaltons) were present. It therefore seems probable that the two large polypeptides (58 and 60 kilodaltons) were precursors of the 40 and 20 kilodalton polypeptides. When the polyadenylated RNA coding for these polypeptides was size fractionated on a sucrose density gradient, it sedimented near the 18S region of the gradient. Translation of the RNA from the gradient fractions and immunoprecipitation of translation products indicated that the template for the 58 to 60 kilodalton ;putative' precursors of oat globulin was probably the RNA which was approximately 18S in size.