RESUMO
Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Células-Tronco de Sangue Periférico , Criança , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/complicações , Mães , Recidiva Local de Neoplasia , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/efeitos adversosAssuntos
Aconselhamento/métodos , Deficiência do Fator X/diagnóstico , Adulto , Feminino , Humanos , Gravidez , Estudos RetrospectivosRESUMO
Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.
Assuntos
Células da Medula Óssea/patologia , Cariotipagem/métodos , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/genética , Manejo de Espécimes/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mieloide/diagnóstico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Transtornos Mieloproliferativos/diagnóstico , Manejo de Espécimes/normas , Adulto JovemRESUMO
INTRODUCTION: Transfusion-dependent anemia and iron overload are associatedwith reduced survival in myelodysplastic syndrome (MDS). This cross-sectional study aimed to evaluate the prevalence of hepatic and cardiac overload in patients with MDS as measured by T2* magnetic resonance imaging (MRI), and its correlation with survival. METHODS: MDS or chronic myelomonocytic leukemia patients had iron overload evaluated by T2* MRI. HIO was considered when hepatic iron concentration ≥ 2 g/mg. Cardiac iron overload was considered with a T2*-value < 20 ms. RESULTS: Among 71 patients analyzed, median hepatic iron concentration was 3.9 g/mg (range 0.9-16 g/mg), and 68%of patients had hepatic iron overload. Patients with hepatic iron overload had higher mean ferritin levels (1182 ng/mL versus 185 ng/mL, p < 0.0001), transferrin saturation (76% versus 34%, p < 0.0001) and lower survival rates. Median cardiac T2*value was 42 ms (range 19.7-70.1 ms), and only one patienthad a T2* value indicative of cardiac iron overload. CONCLUSIONS: Hepatic iron overload is found in two thirds of patients, even in cases without laboratory signs of iron overload. Hepatic iron overload by T2* MRI is associated with a decreased risk of survival in patients with MDS.
Assuntos
Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética , Síndromes Mielodisplásicas/complicações , Miocárdio/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Transformação Celular Neoplásica , Estudos Transversais , Feminino , Humanos , Incidência , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/metabolismo , Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Miocárdio/metabolismo , Prevalência , Avaliação de Sintomas , Adulto JovemRESUMO
Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Manejo de Espécimes/métodos , Síndromes Mielodisplásicas/genética , Células da Medula Óssea/patologia , Leucemia Mieloide/genética , Cariotipagem/métodos , Transtornos Mieloproliferativos/genética , Manejo de Espécimes/normas , Síndromes Mielodisplásicas/diagnóstico , Leucemia Mieloide/diagnóstico , Transtornos Mieloproliferativos/diagnósticoRESUMO
Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection. We also determined salivary and plasmatic concentrations of BU in six HSCT patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. In the patient samples, significant correlations were noted between plasmatic and salivary concentrations of BU (r=0.97, P<0.001 in the test dose; r=0.93, P<0.001 in the adjusted dose). Passing &Bablok regression revealed good agreement between the two methods (R2=0.956 for test dose; R2=0.927 for adjusted dose). In conclusion, the saliva is safe for laboratory BU measurement. The good agreement with plasma encourages further clinical studies using saliva for BU therapeutic monitoring.
Assuntos
Bussulfano/administração & dosagem , Bussulfano/farmacocinética , Transplante de Células-Tronco Hematopoéticas , Saliva/metabolismo , Condicionamento Pré-Transplante , Adulto , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Células-Tronco Fetais/transplante , Doenças Hematológicas/cirurgia , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doenças Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , América Latina , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Gravidez , Adulto JovemRESUMO
Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, â¼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6.81 × 106/kg (range, 0.98-29.78 × 106/kg) in a median of 3 infusions (range, 1-7). Median time between the onset of aGvHD and the first MSC infusion was 25.5 days (range, 6-153). Of the patients, 50% (23/46) presented clinical improvement. Of these, 3 patients (13%) had complete response, 14 (61%) had partial response and 6 (26%) had transient partial response. The estimated probability of survival at 2s year was 17.4%. Only 2 patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion. No patient had late or severe side effects because of MSC infusion. These results suggest that this therapeutic modality is safe and should be considered for steroid-refractory aGvHD, especially in countries where other second-line agents are less available.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Esteroides/administração & dosagem , Taxa de SobrevidaRESUMO
Oral mucositis is a painful condition that occurs in 80% of patients who undergo haematopoietic stem cell transplantation (HSCT). Our objective was to determine the impact of mucositis on quality of life (QoL) of patients subjected to HSCT treated with low-level laser therapy (LLLT). Patients were evaluated: (1) on the first day of treatment; (2) 5 days after autologous or 8 days after allogeneic transplantation; (3) once bone marrow had integrated; and (4) 30 days after discharge. Clinical evaluation was performed using the World Health Organization criteria; oral health QoL was measured using the Oral Health Impact Profile (OHIP-14); and mucositis symptoms with the Patient-Reported Oral Mucositis Symptom (PROMS) scale. The higher the score, the lower the patient's QoL. The OHIP-14 responses showed that at D + 5/D + 8, all domains had the highest scores, while at times 1 and 4, the scores were lower. In the PROMS scale, all domains scored worst at time 2, and the differences between the scores at the four times were statistically significant. The study has shown that QoL improves over time in patients undergoing LLLT therapy for mucositis prevention.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Estomatite/radioterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/terapia , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Estudos Prospectivos , Qualidade de Vida , Adulto JovemRESUMO
Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Ciclofosfamida/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/administração & dosagem , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of Philadelphia chromosome (Ph) leading to expression of a BCR-ABL1 fusion oncogene. The BCR-ABL protein has a constitutive tyrosine kinase activity which is responsible for CML pathogenesis by promoting cell apoptosis resistance; however, the cellular and molecular mechanisms associated with BCR-ABL expression and apoptosis impairment in CML leukemic cells have not been fully elucidated. METHODS: This study evaluated apoptomiRs and their predicted apoptotic genes in BCR-ABL(+) cells from patients in different phases of CML treated with tyrosine kinase inhibitor (TKI) according to their imatinib (IM) response by qPCR. Phosphotyrosine and c-ABL expressions in HL-60.BCR-ABL cells treated with TKI were done by Western blot. RESULTS: We found that dasatinib (DAS) modulated miR-let-7d, miR-let-7e, miR-15a, miR-16, miR-21, miR-130a and miR-142-3p expressions while IM modulated miR-15a and miR-130a levels. miR-16, miR-130a and miR-145 expressions were modulated by nilotinib (NIL). We observed higher miR-15a, miR-130b and miR-145; and lower miR-16, miR-26a and miR-146a expressions in CML-CP in comparison with controls. CML-AP patients showed low miR-let-7d, miR-15a, miR-16, miR-29c, miR-142-3p, miR-145, and miR-146a levels in comparison with CML-CP. We noted that the miR-26a, miR-29c, miR-130b and miR-146a expressions were downregulated in IM resistant patients in comparison with IM responsive patients. CONCLUSIONS: This study showed the modulation of apoptomiRs by BCR-ABL kinase activity and the deregulation of apoptomiRs and their predicted apoptotic target genes in different CML phases and after treatment with TK inhibitors. ApoptomiRs may be involved in the BCR-ABL(+) cell apoptosis regulation.
Assuntos
Apoptose/genética , Benzamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , MicroRNAs/genética , Piperazinas/farmacologia , Pirimidinas/farmacologia , Adolescente , Adulto , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Estudos de Casos e Controles , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosforilação/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Pirimidinas/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.
Assuntos
Antifúngicos/uso terapêutico , Fusariose/tratamento farmacológico , Fusariose/epidemiologia , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Criança , Pré-Escolar , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Fusariose/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Voriconazol/uso terapêutico , Adulto JovemAssuntos
Aconselhamento , Deficiência do Fator X/terapia , Complicações Hematológicas na Gravidez/terapia , Adulto , Fatores de Coagulação Sanguínea/uso terapêutico , Cesárea , Coagulantes/uso terapêutico , Aconselhamento/métodos , Fator X/uso terapêutico , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Ultrassonografia Pré-Natal/métodosRESUMO
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Animais , Soro Antilinfocitário/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Rejeição de Enxerto/prevenção & controle , Mobilização de Células-Tronco Hematopoéticas , Cavalos , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Qualidade de Vida , CoelhosRESUMO
The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions is not an easily determined complication of RBC transfusions. This report discusses one patient who developed RBC autoantibodies in association with an allogeneic blood transfusion and alloimmunization leading to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized as a result of severe anemia and received two units of ABO- and D-compatible RBCs. She had a history of two pregnancies 40 years before, but no history of RBC transfusion, and her antibody screen was negative. On the tenth day after transfusion her hemoglobin dropped, and alloanti-c was identified in her serum and eluate. At this time she received another two units of compatible blood according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3 g/ dL. The direct antiglobulin test was positive, an IgG autoantibody was present in the eluate, and the antibody investigation revealed the presence of anti-Jk(b) in addition to the previously identified alloanti-c. Her genotype was determined, and, based on the findings, two additional units were selected, found to be compatible, and transfused without incident. Transfusions were discontinued, and she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and the patient made an uneventful recovery. It was concluded that transfusion of incompatible RBCs induced the formation of an autoantibody in this patient, resulting in lysis of bystander RBCs. The need for additional blood transfusion was successfully avoided by treatment with IVIG, steroid therapy, and rituximab.
Assuntos
Autoanticorpos/biossíntese , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Eritrócitos/imunologia , Hemólise/imunologia , Reação Transfusional , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antígenos de Grupos Sanguíneos/genética , Incompatibilidade de Grupos Sanguíneos/complicações , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , RituximabAssuntos
Sangue Fetal/citologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/terapia , Mycobacterium tuberculosis/metabolismo , Tuberculose/etiologia , Adulto , Progressão da Doença , Doença Enxerto-Hospedeiro , Doença de Hodgkin/complicações , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Indução de Remissão , Resultado do TratamentoRESUMO
Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in Assuntos
Crise Blástica/tratamento farmacológico
, Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
, Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
, Inibidores de Proteínas Quinases/administração & dosagem
, Pirimidinas/administração & dosagem
, Tiazóis/administração & dosagem
, Administração Oral
, Adolescente
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Antineoplásicos
, Benzamidas
, Terapia Combinada
, Dasatinibe
, Intervalo Livre de Doença
, Resistencia a Medicamentos Antineoplásicos
, Feminino
, Genes abl/genética
, Transplante de Células-Tronco Hematopoéticas
, Humanos
, Mesilato de Imatinib
, Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
, Masculino
, Pessoa de Meia-Idade
, Piperazinas
, Inibidores de Proteínas Quinases/efeitos adversos
, Pirimidinas/efeitos adversos
, Tiazóis/efeitos adversos
, Resultado do Tratamento
, Adulto Jovem
RESUMO
OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Adolescente , Adulto , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/fisiopatologia , Anticorpos Monoclonais Murinos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/fisiopatologia , Brasil , Criança , Quimioterapia Combinada , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/fisiopatologia , Estudos Retrospectivos , Rituximab , Resultado do TratamentoRESUMO
CONTEXT: The hemoglobin (Hb) level is the most-used parameter for screening blood donors for the presence of anemia, one of the most-used methods for measuring Hb levels is based on photometric detection of cyanmetahemoglobin, as an alternative to this technology, HemoCue has developed a photometric method based on the determination of azide metahemoglobin. OBJECTIVE: To evaluate the performance of three methods for hemoglobin (Hb) determination in a blood bank setting. DESIGN: Prospective study utilizing blood samples to compare methods for Hb determination. SETTING: Hemotherapy Service of the Hospital Israelita Albert Einstein, a private institution in the tertiary health care system. SAMPLE: Serial blood samples were collected from 259 individuals during the period from March to June 1996. MAIN MEASUREMENTS: Test performances and their comparisons were assessed by the analysis of coefficients of variation (CV), linear regression and mean differences. RESULTS: The CV for the three methods were: Coulter 0.68%, Cobas 0.82% and HemoCue 0.69%. There was no difference between the mean Hb determination for the three methods (p>0.05). The Coulter and Cobas methods showed the best agreement and the HemoCue method gave a lower Hb determination when compared to both the Coulter and Cobas methods. However, pairs of methods involving the HemoCue seem to have narrower limits of agreement (+/- 0.78 and +/- 1.02) than the Coulter and Cobas combination (+/- 1.13). CONCLUSION: The three methods provide good agreement for hemoglobin determination.