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A Talavera

Publications and source records attributed to A Talavera.

At least 19 recordsLinked to original sources
PubMed2006

Formulation in tablets of a cholera whole cells inactivated vaccine candidate.

Licensed as well as candidate cholera vaccines available at the present requires the dose preparation (included buffer) at the moment of application. The aim of this work was to evaluate the presentation in oral tablets of an inactivated cholera vaccine to avoid that inconveniences during application. We have therefore compared inactivated cultures of Vibrio cholerae with tablets formulation vaccine. We obtained that antigenic activity (ELISA) and immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae inactivated cell remained unaltered in the final tablet formulation. The results suggest that the oral tablet formulation could be a useful pharmaceutical form in order to produce a new and affordable cholera vaccine.

Administration, Oral↗
PubMed2005

Process development for a Cuban cholera vaccine based on the attenuated strain Vibrio cholerae 638.

Genetically modified Vibrio cholerae strain 638 (biotype El Tor, serotype Ogawa) has previously been shown to be immunogenic in animal models and in human trials. Our objective in the work reported herein was to describe the process development methods for the production of the 638 attenuated cholera vaccine. Cell seed bank, culture of biomass, lyophilization and final formulation were processes were developed. The results show kinetics of culture that fulfils a logistical model. The microbiological properties, colonizing capability, immunogenicity and non-toxigenicity of the final product were indistinguishable from the properties of the working seed lot. We conclude that the non-reactogenic, immunogenic and protective strain 638 is robust and can withstand the fermentation processes required for large-scale production of a vaccine.

Animals↗
PubMed2005

Biological modifiers as cytoreductive therapy before stem cell transplant in previously untreated patients with multiple myeloma.

BACKGROUND: High dose chemotherapy with supporting autologous stem cell transplantation is now considered the treatment of choice in patients with multiple myeloma <65 years old. The best regimen appears to be VAD (vincristine, doxorubicin and dexamethasone), but acute and late toxicity can limit the use of this combination. The use of biological modifiers has not been considered in this situation. We developed a new cytoreductive regimen, in an attempt to retain clinical efficacy but reduce toxicity. PATIENTS AND METHODS: Thirty-six patients, previously untreated with diagnosis of multiple myeloma were enrolled to received the DAI regimen (dexamethasone 30 mg/m(2), i.v., days 1-4, all-trans-retinoic acid 45 mg/m(2), p.o., days 5-14 and interferon alpha 2a, 4.5 MU s.c., days 5-14) administered every 28 days for six cycles before high-dose chemotherapy (melphalan 200 g/m(2)) and autologous stem cell transplantation. RESULTS: Overall response was observed in 29 cases (80%), complete response in 19 and partial response in 10 patients. Five patients were >65 years old and were treated with dexamethasone/thalidomide. Twenty-four patients underwent transplants. At a median follow-up of 31.6 months, no relapse or disease progression was observed, thus actuarial curves at 3-years showed that event-free survival was 86% and overall survival was 94%. Toxicity was mild. CONCLUSIONS: This regimen appears to be an excellent alternative as cytoreductive treatment before high-dose chemotherapy and autologous stem cell transplantation with excellent overall response and minimal toxicity. Controlled clinical trials are warranted to define the role of this new therapeutic approach.

Administration, Oral↗
PubMed2001

Evaluation on a six-dose treatment of anti CD 20 monoclonal antibody in patients with refractory follicular lymphoma.

Treatment of refractory follicular lymphoma with monoclonal antibody CD 20 has been proven to be a good therapeutic option. However, most studies used four weekly doses and time to treatment failure (TTF) and overall survival (OS) could be considered very short: 11.0 and 13.6 months respectively. We started a pilot study to evaluate if six infusions at the same doses and schedule could improve the outcome in these patients. Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (> 2 regimens), radiotherapy and biological modifiers were enrolled in a pilot study. They received 6 weekly doses, at 375 mg/m2, of monoclonal anti CD 20. In an intent to treat analysis, overall response was 76%, of which 47% (8 patients) were complete response and 5 patients were partial response. With a median follow-up of 28.6 months, 7 complete responders remain alive, free of disease, and 2 partial responses remain stable without additional treatment. Median to TTF has not been reached; yet, actuarial curves showed that at 3 years, 53% of patients are alive. The four patients who were failure died secondary to tumor progression. Overall survival (OS) at 3-year was 76%. Toxicity was mild, all patients completed the schedule on time and doses. The addition of two doses of anti CD 20 clearly improved OS and TTF in a group of patients with refractory follicular lymphoma heavily treated and with poor prognostic factors. However, the number is too short to draw definitive conclusions; more clinical trials are necessary to determine if 4 or 6 doses of anti CD 20 therapy are better in this setting of patients.

Adult↗
PubMed2001

Chemotherapy plus interferon-alpha2b versus chemotherapy in the treatment of follicular lymphoma.

The best treatment of follicular lymphoma remains to be determined because the long natural history of follicular lymphoma requires mature data for accurate analysis. Although the goal of primary treatment remains durable remission, the sequential application of effective treatments may also result in a prolongation of median survival time. The use of interferon (IFN) with doxorubicin-based chemotherapy has demonstrated an increase of event-free survival but not in overall survival; however, its acute and late cardiac toxicity limits its use. For this reason, we began a controlled clinical trial to assess the efficacy and toxicity of chemotherapy: COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) + IFN alternating every month for six cycles compared to six cycles of chemotherapy. In an intent-to treat analysis, 55 patients were enrolled (median age 61 years). Most cases (91%) with advanced disease were randomly assigned to chemotherapy + IFN (28 cases) or chemotherapy (27 cases). Complete remission was observed in 16 patients: 59% (95% CI, 53-70%) in the chemotherapy arm compared to 20 patients 71% (95% CI, 58-79%) in the chemotherapy + IFN arm; total responses were 74% and 86%, respectively. At a median follow-up of 60 months, event-free survival was 100% for patients treated with chemotherapy + IFN, which was statistically different from patients treated with chemotherapy 70%. At 7 years, median survival has not yet been reached; 72% of patients chemotherapy + IFN remain alive without disease (95% CI, 59-81%), which is not statistically different from 72% (95%CI, 50-73%) in the chemotherapy arm. Non-hematological toxicity was most frequent and severe in the chemotherapy arm; hematological toxicity was similar in both groups. Thus, it appears that chemotherapy + IFN, as described herein, improves event-free survival but the overall survival rates remain unchanged. The use of COPP appears to be better that anthracycline-based chemotherapy because it avoids the presence of acute and late cardiac toxicity.

Adult↗
PubMed2001

Treatment of refractory Hodgkin's disease with modified Stanford V program.

This study analyzes the results using an Stanford V modified program in the treatment of refractory Hodgkin's disease (RHD). We used cyclophosphamide instead of mechloretamine, and epirubicin instead of doxorubicin to avoid the risk of acute and late side effects associated with this drugs. Seventy-one patients with RHD were treated. All were at an advanced stage at therapy and had associated adverse prognostic factors. The complete response (CR) rate was 84% (60 patients; 95% confidence interval [CI]: 72-91%). At 5 yr, actuarial overall survival (CS) is 71% (95% Cl: 59-78%) and event-free survival (EFS) is 70% (95% CI: 59-79%). Only the duration of the initial complete response (> 12 mo) influenced the duration of EFS and OS. Toxicity was mild. Granulocyte colony-stimulating factor to ameliorate the presence of severe myelosuppression was used only in a few patients. Cardiac function was not affected and, until now, late side effects has not been observed. Thus, the use of this modified Stanford program retains the usefulness of the original scheme both with less frequent and less severe acute and late side effects. A controlled clinical trial in untreated patients comparing the Stanford program with standard chemotherapy is warranted to define the role of this therapeutic option in patients with Hodgkin's disease.

Adult↗
PubMed2001

Late lethal events in patients with diffuse large B cell lymphoma: a review of 714 patients treated in a single centre.

Presence of late lethal events has been recognized as a complication in patients with malignant lymphoma. We reviewed 714 cases of patients treated during 1975-1995 with a long term follow-up (>4 years) in an attempt to identify all late events secondary to malignant lymphoma, either to the treatment or those which are unrelated. Forty-three patients died, and of these 21 (2.8%) were secondary to relapse and tumor progression; deaths associated with second neoplasm and cardiac events were increased 9.6 fold and 26.4 fold respectively compared to the general population. The risk factors for these complications did not differ from those in previous reports and included alkylating agents and/or radiotherapy for second neoplasms and anthracycline therapy and radiotherapy for cardiac toxicity. Moreover, 10 patients died secondary to non-related events. Nevertheless, at 10 years overall survival was 94% (95% confidence interval (CI): 82% to 98%) and event free survival was 97.1% (95% CI: 81% to 98%), for these patients. Thus, second events, fatal in most cases, will be considered as an expected risk in the treatment of patients with malignant lymphoma. The proposed modifications of therapy many indeed be useful to avoid or diminish these complications in the future.

Adult↗
PubMed2000

Passive protection of serum from volunteers inoculated with attenuated strain 638 of Vibrio cholerae O1 in animal models.

As part of the studies to obtain an oral vaccine against cholera disease, the protective effect of serum from volunteers inoculated in a controlled trial with a candidate live attenuated vaccine of Vibrio cholerae O1, El Tor Ogawa (638; CTX&phi; mutant, hap::celA), was tested. It was confirmed that the serum, as well as the purified IgG and IgA from the volunteers had a protective effect in both of the animal models used, although the purified antibodies needed the presence of complement to be protective. These results emphasize the expectations about the protective potential of the candidate in challenge studies in humans to be conducted very soon.

Animals↗
PubMed2000

Angiocentric nasal T/natural killer cell lymphoma: a single centre study of prognostic factors in 108 patients.

Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical presentation in North America and Europe but is more common in Asia and Latin America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the nasal cavity with a view to establishing prognostic factors. Most patients were high or high intermediate clinical risk and had additional poor prognostic factors such as bulky disease, high levels of beta 2 microglobulin, advanced stage and multiple extranodal involvement. At 8 years, overall survival was 82%, 90% and 84% for low-intermediate, high-intermediate and high clinical, respectively. Disease free survival was very similar: 79%, 83% and 80%, respectively. Multivariate analysis did not identify any factor influencing overall survival and disease-free survival. There was no evidence that the international prognostic index (IPI) was applicable in these patients and it appears that angiocentric T/NK cell lymphoma is an independent prognostic factor itself.

Adult↗
PubMed2000

In vitro hematopoiesis in patients with malignant lymphoma during active disease and at complete clinical remission after chemotherapy.

Malignant lymphomas are neoplastic diseases of lymphoid cells, which usually originate in the lymph nodes. During the last two decades, significant progress has been made in the characterization of chromosomal and molecular alterations in these malignancies. To date, however, the composition and function of the hematopoietic system in this group of hematological disorders is still not fully understood. In the present study, we have determined the progenitor cell content in 10 patients with diffuse large-cell lymphoma (DLCL) and characterized the proliferation of these cells in long-term marrow cultures. We have also addressed some issues regarding the composition and function of the hematopoietic microenvironment in this malignancy. All the patients included in this study showed normal hematological parameters in peripheral blood, both before and after chemotherapy, however, significant hematopoietic alterations were consistently observed. As compared to normal subjects, lymphoma patients showed a 35% reduction in progenitor cell numbers, including myeloid, erythroid and multipotent progenitors. The in vitro proliferation of these cells was also deficient, since their levels in long-term marrow cultures were significantly lower than those observed in normal bone marrow cultures. Fibroblastic progenitors were reduced by >50% and this correlated with a deficient adherent cell layer development in culture. A reduction was also seen in the levels in culture supernatant of the stimulatory cytokines Stem Cell Factor and Interleukin-6. Interestingly, all the hematopoietic alterations mentioned above were still present in patients at complete clinical remission after chemotherapy. Thus, in the present study we have demonstrated significant in vitro deficiencies in the composition and function of the hematopoietic system in patients with diffuse large-cell lymphoma, both during active disease and at the time of complete clinical remission.

Aged↗
PubMed1999

Interferon as maintenance therapy in refractory malignant lymphoma.

Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy, as less than 20% remain alive and free of disease after 5 years. The use of myeloablative chemotherapy followed by BMT has improved the complete remission (CR) rate. Nevertheless, relapse rates remain unchanged, and only a few patients remain alive and free of disease for more than 3 years. For this reason, we began a prospective randomized clinical trial to determine if IFN-alpha2B (5.0 MU three times a week for 1 year) can improve the prognosis in RML. Ninety-six patients with high or high-intermediate clinical risk RML and in CR after intensive chemotherapy were randomly assigned to receive or not to receive IFN as maintenance therapy. A median follow-up of 48.1 months, the time to treatment failure and survival were similar in both groups. Toxicity secondary to IFN administration was mild, and all patients received the planned doses of IFN. We conclude that IFN is not recommended at this dose and schedule as maintenance therapy in patients with RML who achieve CR. Different therapeutic approaches may be developed to improve outcomes for these patients.

Adult↗
PubMed1999

Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

Adult↗
PubMed1998

Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease.

Adult↗
PubMed1997

Bone marrow protection with amifostine in the treatment of high-risk malignant lymphoma.

Based on preclinical and clinical studies which suggested that amifostine can protect against haematological toxicity of cyclophosphamide, we conducted a clinical trial of amifostine and intermediate doses of cyclophosphamide in patients with high-risk malignant lymphoma. 40 patients were enrolled to receive amifostine (910 mg/m2) before cyclophosphamide (1500 mg/m2) for two cycles (10 patients); 20 patients were allocated to receive amifostine/cyclophosphamide only on one cycle (patients were their own control) and 10 patients received cyclophosphamide alone without amifostine protection. Patients who received amifostine had fewer days of severe granulocytopenia (grade III or IV) and infectious episodes, and delay on treatment was minimal. Amifostine was well tolerated; only 2 patients developed transient and mild hypotension. The complete response rate was 72% (29/40). We conclude that amifostine is a good protector against haematological toxicity of cyclophosphamide and did not interfere with tumour response. Clinical trials with increasing doses of cytotoxic drugs or combination chemotherapy are needed to define the role of this myeloprotector agent in the treatment of patients with malignant lymphoma.

Adult↗
PubMed1997

Epirubicin (CEOP-Bleo) versus idaurubicin (CIOP-Bleo) in the treatment of elderly patients with aggressive non-Hodgkin's lymphoma: dose escalation studies.

One hundred and sixty nine untreated elderly patients (median age 69 years old; range 60-89 years old) with high or high-intermediate clinical risk non-Hodgkin's lymphoma were enrolled in a controlled clinical trial to evaluate escalated doses of epirubicin in a CEOP-Bleo regimen (cyclophosphamide, vincristine, epirubicin, prednisone and bleomycin), compared to escalated doses of idaurubicin in an CIOP-Bleo regimen (idaurubicin instead of epirubicin). Overall, 71% of the patients in the CEOP-Bleo arm achieved a complete response compared to only 48% in the CIOP-Bleo regimen (p < 0.01). At actuarial 3 year, 72% of the patients treated with the CEOP-Bleo regimen remained alive and free of disease, compared to 34% in the CIOP-Bleo arm (p < 0.01). Dose intensity was 0.86 in the epirubicin regimen, similar to 0.82 in the idaurubicin arm. Toxicities were more frequent and severe in the CEOP-Bleo regimen; however, no death-related treatment was observed in either groups. Cardiac toxicity was also similar in both arms. We conclude that treatment of elderly paitents with aggressive non-Hodgkin's lymphoma should be considered a curative attempt and not only palliative. The use of full doses of chemotherapy should be contemplated in elderly patients. Epirubicin, in escalating doses, is a drug with mild toxicity and improvement in outcome in this setting is observed. We cannot confirm the usefulness of idaurubicin, including escalating doses, in the treatment of patients with aggressive malignant lymphoma, because the complete response rate and survival were worse than other chemotherapy regimens. We feel that the CEOP-Bleo regimen with escalated doses of epirubicin is a useful option in the treatment of elderly patients with aggressive non-Hodgkin's lymphoma.

Aged↗
PubMed1997

Dose escalation of epirubicin in the CEOP-BLEO regimen: a controlled clinical trial comparing standard doses for the treatment of diffuse large cell lymphoma.

One hundred and forty-seven consecutive patients with previously untreated high-intermedium and high clinical risk diffuse large cell lymphoma (DLCL) were included in a prospective clinical trial to evaluate the efficacy and toxicity of escalating doses of epirubicin compared to standard doses in the CEOP-Bleo (cyclophosphamide, epirubicin, vincristine and prednisone and bleomycin) regimen, 55% of the patients were > 60 years old and most patients had adverse prognostic factors at diagnosis. Complete response rates were similar in both groups (68% in the standard dose compared to 73% in the escalating arm, (p = 0.5). However, time to treatment failure (TFF) and overall survival were better after escalating doses. At 3-years TTF at a medial follow-up of 33.6 months was 76% in the patients whose received escalating dose statistical different to 37% of the patients whose received standard doses (p < .01). Overall survival was 81% in the escalated therapy arm which is statistical different to 40% of the patients treated with standard doses (p < .01). Toxicity was mild in both arms. Neutropenia, mucositis and cardiotoxicity were mild in the escalated dose arm and no severe complications were observed. All patients received the planned doses of all drugs. Patients > 60 years old had the same CR rate, TTF and overall survival as younger patients. In conclusion it seems that the dose of epirubicin can be increased in combination chemotherapy regimens with safety and only mild toxicity. The CR rate was not superior compared to the standard dose but the TTF and overall survival were better. Longer follow-up periods are required in order to determine if the cure rate can also be improved. Older patients can also benefit because they also tolerated the increase in epirubicin without severe side effects and also improved their outcome. The use of more aggressive regimens with increase in dose intensity may be the treatment of choice for more patients poor prognosis, with DLCL provided there is no increase in toxicity. In this respect the use of epirubicin in higher doses/appears to be useful.

Adult↗