R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group.

BACKGROUND: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. METHODS: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. RESULTS: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P=0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P=0.02). CONCLUSION: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Nordic Myeloma Study Group (NMSG).

One-hundred-and-fifty-one patients with previously untreated multiple myeloma were allocated to treatment with either NOP regimen (mitoxantrone 16 mg/m2 and vincristine 2 mg day 1 and prednisolone 250 mg day 1-4 and 17-20) or M+P regimen (melphalan 0.25 mg/kg and prednisolone 100-200 mg/day day 1-4). Both regimens were repeated every 4 weeks and were scheduled for 1 year. Seventy-seven patients were treated with NOP and 74 patients with M+P. No major clinical differences were recorded between the groups before treatment. Sixty percent of the patients responded (CR+PR) to NOP versus 64% to M+P (NS). The time to progression was 16 months (95% C.L. 14-51) in the NOP group versus 21 months (95% C.L. 15-27) in the M+P group (NS). The median survival was 14 months (7-21) in the NOP group and 31 months (21-43) in the M+P group (p = 0.02). NOP was significantly more toxic than M+P. Seven patients treated with NOP died due to infection and neutropenia and 1 patient died of cardiac toxicity, in contrast to 1 death due to infection and neutropenia in the M+P group. Gastrointestinal toxicity was acceptable in both groups. In conclusion, NOP was inferior to M+P as primary treatment of multiple myeloma.

In vitro cytotoxic effect of alpha-hemolytic Escherichia coli on human blood granulocytes.

The cytotoxic effect of Escherichia coli bacteria on human blood granulocytes was measured by recording numbers of nonlysed cells and percentages of viable cells after in vitro incubation with bacteria in the presence of plasma. A total of 179 strains from various sources of infection were tested. Of 117 alpha-hemolytic strains, 59 were cytotoxic. Five nonhemolytic mutant strains, derived from alpha-hemolytic cytotoxic strains, were nontoxic. None of the 62 nonhemolytic strains were toxic. Four spontaneously occurring alpha-hemolytic, nontoxic mutant strains were isolated from cytotoxic ones. Cytotoxicity of bacteria reached a maximum after log-phase growth at 30 to 37 degrees C for 2.5 h, and the toxic capacity was equal after growth in various media, including human urine and plasma. The cytotoxic effect increased with the length of exposure of granulocytes to bacteria and with increasing numbers of bacteria per granulocyte. Cytotoxic strains showed different degrees of toxicity, highly cytotoxic strains lysing about 90% of the granulocytes and killing about one-half of nonlysed cells in 1 h. Bacteria killed by heat, formaldehyde, or UV light were nontoxic. Alpha-hemolytic strains of O groups 2, 4, 6, 25, and 75 originating from various infections in humans were more frequently cytotoxic than alpha-hemolytic strains of other O groups derived from human infections. Culture supernatants containing free alpha-hemolysin were highly cytotoxic to human blood granulocytes, monocytes, and lymphocytes in vitro, whether supernatants originated from cytotoxic or noncytotoxic bacteria. Cytotoxicity to phagocytes, which is mediated by or closely linked genetically to alpha-hemolysin, may be a mechanism by which alpha-hemolytic strains of E. coli strengthen their ability to establish and maintain infections.

The effect of various immunosuppressive agents on mouse peritoneal macrophages and on the in vitro phagocytosis of Escherichia coli O4:K3:H5 and degradation of 125I-labelled HSA-antibody complexes by these cells.

Large doses of hydrocortisone, cyclophosphamide, and methotrexate injected subcutaneously, and whole-body irradiation (500 rads) caused a reduction in the number of peritoneal cells (PE cells) obtained after intraperitoneal injection of the treated mice with proteose-peptone. The same dose of cyclophosphamide and irradiation induced morphological changes in PE macrophages. There were more giant cells in the peritoneal exudates from treated mice as compared to control mice. 'Pharmacological' and larger doses of hydrocortisone, methotrexate and azathioprine or anti-lymphocyte globulin had no effect on the in vitro phagocytic capacity of proteose-peptone-stimulated mouse PE macrophages. This also applied to doses of up to 50 mg/kg of cyclophosphamide. In contrast, whole-body irradiation (500 rad) and 100 mg/kg of cyclophosphamide decreased the phagocytic capacity of mouse macrophages in vitro and reduced the ability of PE cells to degrade 125I-labelled HSA-antibody complexes in vitro. The greatest effect was noted 4-5 days after whole-body irradiation or four to five subcutaneous injections of cyclophosphamide.