Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients.

BACKGROUND: Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation. PATIENTS AND METHODS: Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission. RESULTS: Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival. CONCLUSION: Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.

Anticancer activities as well as antiviral and virus-enhancing properties of aqueous fruit extracts from fifty-six European plant species.

Several plant-derived drugs are used in medical oncology today. Since only a small part of the flora has been tested for any kind of bioactivity intensive further screening may be rewarding. Fifty-six plant extracts were studied attempting to explore the feasibility of an assay that screens cytotoxic, antiviral and virus-enhancing activities in the same test. We made use of the property of an avian influenza virus replicating in a human breast cancer cell line. During the first 3 days of the test the cytotoxicity of the extracts was evaluated by phase-contrast microscopy. From the 4th day on when viral cytopathogenic effect became manifest we were able to identify antiviral and virus-enhancing activity among some of those extracts not showing cytotoxicity during the first 3 days of incubation. Aqueous extracts from the fruits of 56 plant species belonging to 22 families were screened. Twelve species exhibited cytotoxic, eight antiviral, five virus-enhancing and 31 no activity. These results show that the replication of a myxovirus in a human tumor cell offers the possibility of screening cytotoxic, antiviral and virus-enhancing activity in the same assay.

[Effectiveness and toxicity of high-dosage Ara-C. Clinical observations in 10 cases and review of the literature]. / Wirksamkeit und Toxizität von hochdosiertem Ara-C. Klinische Beobachtungen bei 10 Fällen und Literaturübersicht.

Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.

Interactions of cytotoxic and other drugs: rapid cell culture assay.

In order to investigate the interactions of cytotoxic and other drugs, a cell culture assay was devised where changes in the ability of cytotoxic drugs to induce cytopathogenic effects can easily be visualized. A human mammary carcinoma cell line (BT 20) and a human hypernephroma cell line were used. Seventeen commonly used cytotoxic drugs were titrated in this assay. As an example of drug interactions the neutralization of nitrogen mustard, cis-dichlorodiammine-platinumII, and 4-hydroperoxycyclophosphamide by thiol-containing drugs shows that this assay is well suited to detect interactions of cytotoxic and other drugs.