Assuntos
Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva , Pioglitazona/administração & dosagem , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Quantification of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) can be time-consuming. We evaluated the performance of an automatic multifocal segmentation (MFS) method of quantification in patients with different stages of Hodgkin lymphoma, using the multiple VOI (MV) method as reference. Methods: This prospective bicentric study included 50 patients with Hodgkin lymphoma who underwent staging 18F-FGD PET/CT. The examinations were centrally reviewed and processed with commercial MFS software to obtain MTV and TLG using 2 fixed relative thresholds (40% and 20% of SUVmax) for each lesion. All PET/CT scans were processed using the MV and MFS methods. Interclass correlation coefficients and Bland-Altman plots were used for statistical analysis. Repeated calculations of MTV and TLG values by 2 observers with different degrees of PET/CT imaging experience were used to ascertain interobserver agreement on the MFS method. Results: The means and SDs obtained for the MTV with MV and MFS were, respectively, 736 ± 856 mL and 660 ± 699 mL for the 20% threshold and 313 ± 359 mL and 372 ± 434 mL for the 40% threshold. The time spent calculating the MTV was much shorter with the MFS method than with the MV method (median time, 11.6 min [range, 1-30 min] and 64.4 min [range, 1-240 min], respectively), especially in patients with advanced disease. Time spent was similar in patients with localized disease. There were no statistical differences between the MFS values obtained by the 2 different observers. Conclusion: MTV and TLG calculations using MFS are reproducible, generate similar results to those obtained with MV, and are much less timing-consuming. Main differences between the 2 methods were related to difficulties in avoiding overlay of VOIs in the MV technique. MV and MFS perform equally well in patients with a small number of lesions.
Assuntos
Fluordesoxiglucose F18/farmacologia , Doença de Hodgkin/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/farmacologia , Carga Tumoral/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Fluordesoxiglucose F18/química , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos/química , Estudos Retrospectivos , Fatores de TempoAssuntos
Doença de Hodgkin/genética , Neovascularização Patológica/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Glutationa Transferase/genética , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Adulto JovemRESUMO
OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.
Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Exame de Medula Óssea , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome ...
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/uso terapêutico , Exame de Medula Óssea , Intervalo Livre de Doença , Proteínas de Fusão bcr-abl/genética , Estimativa de Kaplan-Meier , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Resultado do TratamentoRESUMO
The objective of this case report is to present a rare association of a mucosa-associated lymphoid tissue lymphoma masquerading as Graves' orbitopathy in a patient with autoimmune hyperthyroidism, without evidence of Graves' ophthalmopathy. A 66-year-old male patient had pain and swelling of the right eye. Evaluation of serum thyroid hormone revealed low thyrotropin, elevated free thyroxin and antithyroperoxidase antibody levels, confirming the diagnosis of Graves' disease. Computed tomographic scan showed intraorbital muscle asymmetry. Biopsy demonstrated a low-grade, B-cell type non-Hodgkin's lymphoma of the mucosa-associated lymphoid tissue. Treatment included radiotherapy and chemotherapy, with regression of the orbital lesion and medical treatment with methimazole and (131)I. Detailed orbital evaluation should be considered in all patients who present any atypical signs and symptoms of the eyes, to prevent missing important and progressive diagnoses.
Assuntos
Doença de Graves/diagnóstico , Linfoma/diagnóstico , Neoplasias Orbitárias/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
We examined the influence of the glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1), and pi 1 (GSTP1) polymorphisms, which are involved in the metabolism of alkylating agents and anthracyclines, on the outcome of patients with Hodgkin lymphoma (HL) treated with conventional chemotherapy. Genomic DNA from 125 consecutive cases was analyzed by polymerase chain reaction and enzymatic digestion for polymorphism determination. The GSTM1 undeleted genotype was associated with more advanced tumor stage and worse disease-free survival. The GSTT1 undeleted genotype was associated with higher recurrence rate. In contrast, higher toxicity of chemotherapy was attributed to absence of the GSTT1 gene. Concerning overall survival, lower tumor stage (pâ=â0.006) and International Prognostic Score (pâ=â0.02), lower peripheral leukocyte count (pâ=â0.0003), higher serum albumin level (pâ=â0.08), and GSTT1 undeleted genotype (pâ=â0.04) were predictive of a better outcome of patients. In multivariate analysis comparing staging and GST polymorphism, only tumor stage and GSTT1 genotype remained in the model. Our results suggest that the GSTT1 polymorphism influences the outcome of Brazilian patients with HL. However, studies of toxicity, pharmacokinetics, and protein function may clarify whether carriers of the distinct genotypes should receive different doses of chemotherapeutic agents.
Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Optimization of peripheral blood stem cell (PBSC) collection for autologous bone marrow transplantation is necessary for a good standard of care and cost-effectiveness. An algorithm was validated for prediction of the day of maximum peripheral CD34+ cell concentration after mobilization chemotherapy (Day(CD34peak)). STUDY DESIGN AND METHODS: This study compared mobilization and collection variables of a cohort of patients where apheresis was started at the Day(CD34peak) predicted by the algorithm with a patient group where PBSCs were collected when PB CD34+ cell concentration reached 10 per microL per day (Day(CD34threshold)). Day(CD34peak) was calculated according to the equation Day(CD34peak) = -0.41 x Hb(D0) + 0.99 x Day(CD34threshold) + 7.8 (with Hb(D0) representing the hemoglobin value on Day 0). RESULTS: The mean number of apheresis procedures per patient based on the Day(CD34threshold) was 1.74, but decreased to 1.35 when applying the new method (Day(CD34peak)). For lymphomas, the mean number of apheresis procedures decreased from 1.98 to 1.47 (p = 0.03), while in patients with multiple myeloma it did not change significantly (1.23 and 1.26, respectively). Age and primary disease influenced the number of apheresis procedures needed to achieve the collection target. CONCLUSION: The application of our algorithm can lower the number of apheresis procedures by improving the timing, especially in patients suffering from malignant lymphomas with a poor marrow potential after several chemotherapy lines.
Assuntos
Algoritmos , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos/métodos , Hemoglobinas/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
O imatinibe tem sido confirmado como terapia de primeira linha para a Leucemia Mielóide Crônica (LMC) por apresentar respostas duradouras na maior parte dos pacientes, principalmente nos que se encontram em fase precoce da doença. Entretanto, resistência ou intolerância ao imatinibe podem ocorrer. A resistência ao imatinibe ocorre com muito mais freqüência em fases mais avançadas da doença, sendo a causa mais comum o desenvolvimento de mutações no sítio BCR-ABL. Em face deste problema, novos inibidores de tirosino quinase têm sido desenvolvidos, com maior potência, diminuindo assim a chance de desenvolvimento de resistência ao tratamento. O nilotinibe e o dasatinibe são dois exemplos de inibidores de segunda geração de tirosino quinase recentemente aprovados. Ambos têm demonstrado excelentes resultados em pacientes que desenvolvem resistência ou são intolerantes ao imatinibe.
Despite the success with imatinib as the first choice treatment of chronic myeloid leukemia (CML), there is still a subset of patients that do not respond optimally to or are intolerant of this drug or lose response. Imatinib resistance can occur at any phase, but it is more frequent in advanced phases, with mutations in the BCR-ABL kinase domain being the most common mechanism of resistance. More potent tyrosine kinase inhibitors have been developed that can overcome resistance to imatinib. Nilotinib and dasatinib are good examples of new tyrosine kinase inhibitors that are available. With these new agents, patients who develop imatinib resistance or those unable to tolerate imatinib treatment can achieve significant clinical responses.