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2.
J Cancer Res Clin Oncol ; 142(1): 305-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26407768

RESUMO

INTRODUCTION: Treatment of patients (pts) with acute myelogenous leukaemia (AML) above 60 years remains a challenge. We report long-term follow-up of the AML97 study, where pts were registered at diagnosis and received treatment dependent on their comorbidities: dose-intense cytarabine (AraC) and anthracycline in the curative arm, and low-dose chemotherapy in the palliative arm or best supportive care. MATERIALS AND METHODS: A total of 618 pts were enrolled in this protocol (curative 471, palliative 115 and supportive 32). In the curative arm, complete remission (CR) was obtained in 66.8 % of pts and the estimated probability of being alive at 2 years was 0.30 (±0.02 SE). In multivariate analysis, gender (p = 0.005), performance status (p = 0.04) and cytogenetics (p = 0.002) were significant factors for CR. With a median follow-up of 10 (range 0.1-11.8) years, the estimated probability of being event-free after 2 and 5 years according to cytogenetics was 0.48 ± 0.11 and 0.48 ± 0.11 for favourable, 0.20 ± 0.03 and 0.09 ± 0.03 for normal, 0.18 ± 0.06 and 0.10 ± 0.05 for other standard risk and 0.10 ± 0.03 and 0.05 ± 0.02 for unfavourable karyotypes, respectively. The median survival time for pts treated with palliative chemotherapy was 54 and 11 days with best supportive care only. CONCLUSION: In conclusion, treatment of older AML pts with dose-intense AraC is feasible in the majority of pts and induces high rates of CR. Nevertheless, except for favourable karyotype, OS and event-free survival remain low. These results need to be viewed in relation to the new modalities including stem cell transplantation following non-myeloablative conditioning, epigenetic and molecular therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Alemanha , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo
3.
Bone Marrow Transplant ; 51(2): 212-218, 2016 02.
Artigo em Inglês | MEDLINE | ID: mdl-26569093

RESUMO

Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma/mortalidade , Linfoma/terapia , Sistema de Registros , Transplante de Células-Tronco , Tiotepa/administração & dosagem , Adolescente , Adulto , Idoso , Autoenxertos , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida
4.
Leukemia ; 30(3): 562-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26464170

RESUMO

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Risco , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
5.
Bone Marrow Transplant ; 49(3): 410-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24362366

RESUMO

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Bussulfano/administração & dosagem , Bussulfano/análogos & derivados , Carboplatina/administração & dosagem , Progressão da Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Fatores de Risco , Rituximab , Condicionamento Pré-Transplante , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
6.
J Cancer Res Clin Oncol ; 138(3): 513-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22198675

RESUMO

PURPOSE: Single-dose pegylated filgrastim (pegfilgrastim) after autologous hematopoietic stem cell transplantation (AHSCT) showed similar efficacy compared to daily lenograstim. To address the question of the optimal application time, we randomly assigned patients (pts) to pegfilgrastim on day + 1 (Peg1) or day + 4 (Peg4) after AHSCT. METHOD: Fifty-three pts with different hematological malignancies were included in this prospective randomized multicenter study. Primary endpoint of this study was time to neutrophil recovery (>500 Gpt/l), and secondary endpoint was time to neutrophil recovery (>1,000 Gpt/l), platelet recovery (>20,000 Gpt/l), number and duration of febrile episodes, i.v. antibiotics, and number of transfusions. Time to engraftment endpoints were estimated according to Kaplan-Meier. RESULTS: Median time to neutrophil recovery (>500 Gpt/l) was 10 days (95% CI: 10-11) in Peg1 versus 10 days (95% CI: 10-11) in Peg4 (P = 0.68, logrank test; hazard ratio: 0.93). The corresponding mean values were 10.2 and 10.4 days. Median time to platelet recovery (>20,000 Gpt/l) was 10 (95% CI: 10-11) in Peg1 versus 10 (95% CI: 9-11) in Peg4, again not significantly different (P = 0.54). There was no difference regarding the incidence (67% vs. 60%, P = 0.77, Fisher's exact test) or duration of febrile neutropenia episodes in both groups (median: 1 vs. 1; mean: 2.8 vs. 2.4 days; P = 0.73, Wilcoxon test). CONCLUSION: In terms of neutrophil or platelet recovery after AHSCT, number and duration of febrile episodes, the use of i.v. antibiotics, early and late administration of pegfilgrastim are equally effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Neutropenia/tratamento farmacológico , Adulto , Idoso , Antibacterianos/administração & dosagem , Transfusão de Sangue/estatística & dados numéricos , Esquema de Medicação , Feminino , Febre/etiologia , Filgrastim , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/cirurgia , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Lenograstim , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Neutropenia/prevenção & controle , Polietilenoglicóis , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Transplante Autólogo , Resultado do Tratamento
7.
Clin Exp Dermatol ; 34(5): e72-4, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19438525

RESUMO

Legionnaires' disease is an acute bacterial infection, generally caused by Legionella pneumophila, which primarily involves the lower respiratory tract, although it is often associated with multisystemic extrapulmonary features. Cutaneous features are very uncommon and may include erythematous or petechial, macular or maculopapular lesions. We report a male patient who expressed all features of a severe lobular pneumonia. Over the course of the disease the patient developed a livid erythematous, maculopapular exanthem rapidly extending over the entire body. Given the rapid development and target-like appearance of the skin lesions with extensive skin involvement and blister formation, the initial diagnosis was that of a severe cutaneous drug reaction. However, histological examination of biopsy did not confirm this diagnosis, but instead was suspicious for a viral exanthem or a more aggressive inflammatory response due to sensitization to bacterial antigens. L. pneumophila infection was verified during the course of the disease.


Assuntos
Toxidermias/diagnóstico , Exantema/diagnóstico , Doença dos Legionários/diagnóstico , Dermatopatias Bacterianas/diagnóstico , Diagnóstico Diferencial , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
8.
Leukemia ; 23(4): 635-40, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19151786

RESUMO

Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Cariotipagem , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
9.
J Cancer Res Clin Oncol ; 133(6): 411-5, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17245594

RESUMO

PURPOSE: The study investigated in detail neutrophil functions shortly after allogeneic peripheral blood stem cell transplantation (PBSCT). METHODS: Different functions of neutrophils in 14 patients who received allogeneic PBSCT were investigated. The migratory capacity as well as the ability to induce oxidative burst following stimulation with either Phorbol-12-myristate-13-acetate (PMA), the chemotactic peptide N-formyl-Met-Leu-Phe (f-MLP) or opsonized Escherichia coli was analysed after engraftment (between day +30 and +40) and compared with the results obtained from healthy volunteers. RESULTS: There are no differences in terms of the migratory capacity (P = 0.17), as well as regarding the oxidative burst after incubation with PMA (P = 0.08) or f-MLP (P = 0.06), compared with healthy men. In contrast, the capacity of neutrophils to induce oxidative burst following stimulation with E. coli is highly impaired (P = 0.0001) in patients shortly after engraftment. CONCLUSION: The recovery of neutrophils after allogeneic PBSCT is not only influenced by the varying time of engraftment, but also represents a process that differs in distinct biological functions compared to normal granulopoieses.


Assuntos
Quimiotaxia de Leucócito , Neutrófilos/imunologia , Transplante de Células-Tronco de Sangue Periférico , Explosão Respiratória , Adulto , Movimento Celular , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Fagocitose , Condicionamento Pré-Transplante
10.
Pharmazie ; 61(11): 957-61, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17152990

RESUMO

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.


Assuntos
Circulação Coronária/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Doença Aguda , Idoso , Quimiocina CCL2/sangue , Quimiocinas/biossíntese , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Prospectivos , Ventriculografia com Radionuclídeos , Compostos Radiofarmacêuticos , Volume Sistólico/fisiologia , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único , Fator A de Crescimento do Endotélio Vascular/sangue
11.
Acta Haematol ; 116(1): 58-61, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16809891

RESUMO

We report on a 54-year-old male patient with an aggressive T cell non-Hodgkin's lymphoma with abdominal manifestation undergoing autologous peripheral blood stem cell transplantation after high-dose chemotherapy in April 2003. About 4 months after transplantation, he developed severe upper abdominal pain. Ultrasound examination, X-ray, computed tomography of the abdomen and cardiac diagnostics could not explain the symptoms. While empiric therapy with high-dose acyclovir was started, we could document herpetic lesions in the gastric antrum by endoscopy. The epigastric pain rapidly decreased within several days after the start of acyclovir therapy. No herpetic skin lesions were observed at any time during the disease. This report demonstrates the importance of viral-induced gastritis in the differential diagnosis of severe abdominal pain in patients receiving autologous peripheral blood stem cell transplantation.


Assuntos
Abdome Agudo/tratamento farmacológico , Aciclovir/administração & dosagem , Antivirais/administração & dosagem , Gastrite/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Linfoma não Hodgkin/terapia , Abdome Agudo/diagnóstico , Abdome Agudo/etiologia , Abdome Agudo/virologia , Diagnóstico Diferencial , Gastrite/diagnóstico , Gastrite/etiologia , Gastrite/virologia , Gastroscopia , Herpes Zoster/diagnóstico , Herpes Zoster/etiologia , Humanos , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Antro Pilórico/virologia , Transplante Autólogo
12.
Pneumologie ; 59(11): 763-9, 2005 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-16385437

RESUMO

Pulmonary fibrosis (PF) may develop following successful chemotherapy for malignancy, even if such therapy is not combined with radiotherapy. Bleomycin, which is known to induce acute pneumonitis and lung fibrosis, is especially associated with chemotherapy-induced PF, and bleomycin-induced pulmonary fibrosis can occur more than five years after such therapy. Additionally, supplemental oxygen therapy can trigger the onset of pneumonitis and lethal PF in patients who have previously received bleomycin therapy. Careful assessment of lung function via spiroergometry and arterial blood gas analysis during exercise are required if the administration of supplemental oxygen is considered. Two case reports reveal the potential lethal risk of oxygen for patients who have been treated with bleomycin: (1) a patient with successfully resected and treated basal tongue carcinoma and (2) a patient in remission after being treated for non-Hodgkin lymphoma. Single and double lung transplantation is the only therapeutic option for patients with severe, oxygen-induced PF and should be included as an indication for lung transplantation. Early recognition of pulmonary diffusion abnormalities and establishing a risk profile, as well as consequent monitoring of pulmonary function, may help to avoid or at least reduce the risk of PF induced by oxygen therapy when administered to patients who have previously been given bleomycin.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Fibrose Pulmonar/induzido quimicamente , Insuficiência Respiratória/induzido quimicamente , Adulto , Bleomicina/efeitos adversos , Gasometria , Feminino , Humanos , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/prevenção & controle , Testes de Função Respiratória , Insuficiência Respiratória/prevenção & controle
13.
Curr Pharm Des ; 11(27): 3531-43, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16248806

RESUMO

To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with >3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.


Assuntos
Vacinas Anticâncer/uso terapêutico , Indústria Farmacêutica/tendências , Motivação , Regressão Neoplásica Espontânea/imunologia , Observação/métodos , Antígenos de Neoplasias , Vacinas Anticâncer/imunologia , Testes Imunológicos de Citotoxicidade/métodos , Indústria Farmacêutica/economia , Indústria Farmacêutica/métodos , Humanos , Antígeno MART-1 , Melanoma/imunologia , Melanoma/patologia , Melanoma/terapia , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/imunologia , Regressão Neoplásica Espontânea/genética , Regressão Neoplásica Espontânea/patologia , Neoplasias Primárias Desconhecidas/imunologia , Linfócitos T Citotóxicos/imunologia , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/tendências
14.
Bone Marrow Transplant ; 35(2): 183-90, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15531897

RESUMO

Dose-reduced allogeneic peripheral blood stem cell transplantation (PBSCT) is a therapeutic approach for patients with haematological malignancies who are not eligible for conventional allogeneic PBSCT. We analysed early development of lymphocyte subpopulations and the occurrence of cytomegalovirus (CMV) reactivation and acute graft-versus-host reaction (GvHD) in patients undergoing the protocol according to Slavin vs conventionally treated patients. Lymphocyte status prior to conditioning and at day +30 after allogeneic PBSCT was determined in 24 out of 51 patients who received conventional allogeneic PBSCT (eg cyclophosphamide plus total body irradiation) and compared with 27 patients being treated according to the Slavin protocol (fludarabine, busulphan and ATG). There is a significant delay in CD4 (T helper) cell development and consecutive lower CD4/CD8 ratios and a better reconstitution of CD8 (T cytotoxic) and NK (natural killer) cells after the Slavin protocol. Patients undergoing this protocol and no, or only grade I, acute GvHD show an even better NK cell reconstitution compared to patients with grade II-IV GvHD. A low CD4/CD8 ratio represents a CMV risk factor only in conventionally treated patients with grade 0-I GvHD, while after preparative regimen according to the Slavin protocol, the NK/CD8 ratio might be a marker for the prediction of CMV reactivation in addition to CMV risk status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por Citomegalovirus/etiologia , Doença Enxerto-Hospedeiro/etiologia , Células Matadoras Naturais/fisiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adulto , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Ativação Viral
15.
Mol Cell Biochem ; 260(1-2): 1-5, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15228079

RESUMO

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.


Assuntos
Adenocarcinoma Folicular/sangue , Adenocarcinoma Papilar/sangue , Neoplasias da Glândula Tireoide/sangue , Oligoelementos/sangue , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/cirurgia , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Fatores de Tempo
16.
Dtsch Med Wochenschr ; 129(9): 424-8, 2004 Feb 27.
Artigo em Alemão | MEDLINE | ID: mdl-14970913

RESUMO

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.


Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Coração/fisiologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Infarto do Miocárdio/terapia , Regeneração/efeitos dos fármacos , Adulto , Idoso , Angioplastia Coronária com Balão , Eletrocardiografia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Revascularização Miocárdica/métodos , Stents , Tomografia Computadorizada de Emissão , Tomografia Computadorizada de Emissão de Fóton Único , Função Ventricular Esquerda/fisiologia
17.
Bone Marrow Transplant ; 33(1): 65-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14704658

RESUMO

In this open single-centre phase II study, MMF was added on day +10 after allogeneic transplantation to standard immunosuppressive prophylaxis consisting of cyclosporine and methotrexate to decrease the incidence of GvHD. In all, 30 patients aged 20-59 years with advanced haematological malignancies received an unmanipulated blood-stem-cell graft (median of 8.5 x 10(6) CD34(+) and 349 x 10(6) CD3(+) cells per bodyweight) from matched unrelated (n=26), or mismatched donors (n=4). Prior to transplantation, 13 patients underwent fractionated total body irradiation and cyclophosphamide, one patient additional etoposide. In all, 16 patients received reduced conditioning of fludarabin, busulfan, and antithymocyte globulin. All patients engrafted in a median of 12 days, and 19 developed acute GvHD>/=II, including two patients with GvHD III and three with GvHD IV. Subsequently, nine patients developed limited and two patients extensive chronic GvHD. With a median follow-up of 28 months, the overall survival is 53.3% and disease-free survival 50%, respectively. Only two deaths were due to GvHD IV. Out of 13 patients, 10 being CMV IgG positive became positive for pp65. In conclusion, this MMF schedule seems to be safe and feasible in the prophylaxis of severe acute GvHD for high-risk patients, restricted by an increased risk for reactivating CMV in seropositive patients.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Doadores de Sangue , Ciclosporina/administração & dosagem , Citomegalovirus/fisiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Fatores de Tempo , Transplante Homólogo , Ativação Viral
19.
Leukemia ; 17(12): 2392-400, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14523462

RESUMO

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.


Assuntos
Antineoplásicos/administração & dosagem , Proteínas de Fusão bcr-abl/genética , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Benzamidas , Estudos Cross-Over , Citarabina/administração & dosagem , Citogenética , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , RNA Mensageiro/metabolismo , Recidiva , Fatores de Risco , Resultado do Tratamento
20.
MMW Fortschr Med ; 145(24): 40-2, 2003 Jun 12.
Artigo em Alemão | MEDLINE | ID: mdl-12866298

RESUMO

Modern treatment of cancer of the breast is based on established prognostic factors (patient age, receptor status, tumor size, lymph node involvement, tumor grading), and thus takes the patient's individual risk profile into account. In addition to the antiestrogen, tamoxifen, new hormonal preparations, such as the aromatase inhibitors, hold out promise of improved results from adjuvant treatment in elderly women. In premenopausal women, additional hormone blockade by means of GnRH analogs is of advantage. Neoadjuvant (preoperative) chemotherapy protocols will enable rapid evaluation of new therapeutic options. When metastases have developed, treatment with hormonal drugs is indicated in the case of slowly progressing disease (low risk), while clinically progressive metastasization (high risk) requires cytostatic chemotherapy. Here, studies involving more recent substances with improved tolerability, and tumor-specific antibodies, confirm an improvement in the prognosis. The concentration of drug treatment in interdisciplinary centers is a necessary element of quality assurance and therapeutic optimization.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Antagonistas de Estrogênios/uso terapêutico , Imunoterapia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Adulto , Fatores Etários , Idoso , Anastrozol , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Letrozol , Metanálise como Assunto , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Nitrilas/uso terapêutico , Pré-Menopausa , Prognóstico , Qualidade da Assistência à Saúde , Cloridrato de Raloxifeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Tamoxifeno/uso terapêutico , Fatores de Tempo , Toremifeno/uso terapêutico , Trastuzumab , Triazóis/uso terapêutico
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