Assuntos
Glutationa Transferase/genética , Mieloma Múltiplo , Polimorfismo de Nucleotídeo Único , Transplante de Células-Tronco , Talidomida/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Taxa de SobrevidaAssuntos
Glutationa S-Transferase pi/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Mutação de Sentido Incorreto , Polimorfismo Genético , Substituição de Aminoácidos , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Prednisona/administração & dosagem , Estudos Prospectivos , Rituximab , Taxa de Sobrevida , Pesquisa Translacional Biomédica , Vincristina/administração & dosagemAssuntos
Transplante de Células-Tronco Hematopoéticas , Reação em Cadeia da Polimerase em Tempo Real , Quimeras de Transplante , Adulto , Deleção de Genes , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Mutação INDEL , Recidiva Local de Neoplasia/diagnóstico , Polimorfismo Genético , Células-Tronco/citologia , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
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 JovemRESUMO
Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/complicações , Micoses/epidemiologia , Síndromes Mielodisplásicas/complicações , Transplante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus/isolamento & purificação , Brasil/epidemiologia , Candida/isolamento & purificação , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fusarium/isolamento & purificação , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Síndromes Mielodisplásicas/terapia , Adulto JovemRESUMO
The aim of this study was to evaluate taste perception, salivary flow rate and oral pathologies in three different groups of patients undergoing hematopoietic SCT (HSCT) classified according to time post transplant. Group I (n=20) up to 150 days after HSCT, group II (n=20) between 151 and 1095 days and group III (n=21) more than 1095 days. Taste acuity was measured by four basic tastes of four solutions, in three concentrations (M): NaCl, sucrose, citric acid and caffeine. Patients classified flavors as sweet, sour, salty, bitter and without flavor. The intensity was considered high, medium and low. Unstimulated saliva was collected and salivary flow rates (ml/min) were determined. Of 61 patients, 31 had chronic GVHD. For the sweet solution, the high and low concentrations represented a challenge for those patients. No patients were sensitive to the low concentration of caffeine solution (P=0.05). Saliva flow rate was diminished in 10 of 61 (16%) patients and hyposalivation was more intense in groups II/III (P=0.007). There was no correlation between taste dysfunction and oral chronic GVHD. The results indicated taste alterations only for the sweet and salty tastes even in patients up to 3 years after HSCT and may not correlate with oral chronic GVHD and with hyposalivation.
Assuntos
Disgeusia/etiologia , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Xerostomia/etiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Disgeusia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Limiar Gustativo , Xerostomia/diagnóstico , Adulto JovemRESUMO
INTRODUCTION: Risk factors traditionally associated with kidney graft dysfunction after transplantation are delayed graft function, acute cellular rejection episodes, deceased donor organ source (particularly more than 50 years old), and HLA mismatch. Socioeconomic factors, such as income, education, and type of health insurance, have been reported in some studies. OBJECTIVE: To evaluate the risk factors traditionally associated with worse function of the transplanted kidney and the role of socioeconomic variables among our population. DESIGN OF STUDY: A cohort with 69 patients transplanted in the period 2003 to 2006 was assessed for predictors for a creatinine clearance estimated to be less than 60 mL/min or stage 3 or greater of renal dysfunction at 1 year of follow-up. CONCLUSION: Upon bivariate regression analysis, acute tubular necrosis [odds ratio (OR) 6.93 (1.9-24), P = .03], and bacterial infection [OR 4.13 (1.4-12), P < .01] were predictors of risk, which was also observed among transplants of kidneys from deceased donors [OR 2.67 (0.9-7.6), P = .07] or donors aged more than 49 years [OR 4.22 (0.9-18.1), P = .06]. Better education was a significant protective factor [OR 0.3 (0.1-0.9), P = .02]. Upon multivariate logistic regression analysis delayed graft function [OR 5.1 (1.3-20.5), P = .02] and severe bacterial infection [OR 3.9 (1.23-12.9), P = .02] were predictors; there was no association with socioeconomic factor.
Assuntos
Transplante de Rim/fisiologia , Complicações Pós-Operatórias/epidemiologia , Infecções Bacterianas/epidemiologia , Brasil , Cadáver , Estudos de Coortes , Creatinina/metabolismo , Escolaridade , Feminino , Humanos , Renda , Transplante de Rim/efeitos adversos , Túbulos Renais/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Regressão , Terapia de Substituição Renal , Fatores de Risco , Fatores Socioeconômicos , Doadores de TecidosRESUMO
Stability of the quantized Hall phases is studied in weakly coupled multilayers as a function of the interlayer correlations controlled by the interlayer tunneling and by the random variation of the well thicknesses. A strong enough interlayer disorder destroys the symmetry responsible for the quantization of the Hall conductivity, resulting in the breakdown of the quantum Hall effect. A clear difference between the dimensionalities of the metallic and insulating quantum Hall phases is demonstrated. The sharpness of the quantized Hall steps obtained in the coupled multilayers with different degrees of randomization was found consistent with the calculated interlayer tunneling energies. The observed width of the transition between the quantized Hall states in random multilayers is explained in terms of the local fluctuations of the electron density.
RESUMO
Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65% of the samples (group 1), while 35% of the samples expressed primarily APAF-1LN (group 2). Only 46% of the patients presented complete remission in response to remission induction therapy (represented by less than 5% marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6% did not attain complete remission (only 1 case from group 1), and 32.4% of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia.
Assuntos
Fator Apoptótico 1 Ativador de Proteases/genética , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Células da Medula Óssea/química , Estudos de Casos e Controles , DNA Complementar/genética , Densitometria , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição , Transcrição Gênica/genética , Falha de Tratamento , Adulto JovemRESUMO
Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65 percent of the samples (group 1), while 35 percent of the samples expressed primarily APAF-1LN (group 2). Only 46 percent of the patients presented complete remission in response to remission induction therapy (represented by less than 5 percent marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6 percent did not attain complete remission (only 1 case from group 1), and 32.4 percent of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fator Apoptótico 1 Ativador de Proteases/genética , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células da Medula Óssea/química , Estudos de Casos e Controles , Densitometria , DNA Complementar/genética , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/tratamento farmacológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/genética , Fatores de Transcrição , Falha de Tratamento , Transcrição Gênica/genética , Biomarcadores Tumorais/genética , Adulto JovemRESUMO
This study aimed to analyse the association of gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. We studied 122 donor/recipient pairs who received HLA-identical transplants from siblings at the Universidade Estadual de Campinas, Brazil, between June 1996 and June 2006. Donor/recipient alleles for TNFA-238 and IL2-330/+166 single-nucleotide polymorphisms (SNP) were analysed by PCR-SSP. No association was observed between the risk of acute graft-versus-host disease (GVHD) and these SNP. However, our findings suggest that the polymorphism of promoter gene TNFA-238GA is associated with the occurrence and severity of chronic GVHD. The probability of chronic GVHD in patients with GA genotype at position -238 of TNFA gene is 91.7% in contrast to 59.4% in patients with GG genotype (P = 0.038). In patients with donor GA genotype the probability of chronic GVHD is 90.8%, and 57.9% in patients with donor GG genotype (P = 0.038). The probability of extensive chronic GVHD in patients with TNFA-238GA is 91.7% compared with 46.3% in patients with TNFA-238GG (P = 0.0046). In patients with donor GA genotype at position -238 of the TNFA gene, it is 81.7%, compared with 44.5% in patients with donor GG genotype (P = 0.016). However, further studies with more patients are required to identify cytokine gene polymorphisms and their association with transplant-related complication in Brazil, particularly due to ethnic background, the relatively low power of detection of genetic markers of this study, and the complexity of the MHC region.
Assuntos
Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interleucina-2/genética , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Adulto , Brasil , Criança , Feminino , Genótipo , Doença Enxerto-Hospedeiro/imunologia , Humanos , Lactente , Interleucina-2/imunologia , Leucemia/genética , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/imunologia , Irmãos , Doadores de Tecidos , Transplante Homólogo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
INTRODUCTION: Chronic graft-vs-host disease (cGVHD) is a major cause of morbidity in long-term survivors of allogeneic hematopoietic progenitor cell transplantation. Herpesviruses are involved in the occurrence and progression of various oral diseases. AIM: The aim of this study was to investigate the role of human herpesvirus 6 (HHV6) in patients with oral manifestations of cGVHD. MATERIALS AND METHODS: Peripheral blood and oral fluids (whole saliva, gingival crevicular fluid and parotid gland saliva) from 19 cGVHD patients, and 28 blood donors were examined for HHV6. Oral tissue samples were collected from 12 cGVHD patients and 12 healthy individuals. Nested polymerase chain reaction was employed to identify the HHV6. RESULTS AND CONCLUSION: The virus was detected in whole saliva in 13 cGVHD patients (68%) and in 19 blood donors (67%). HHV6 was not identified in any of the gingival crevicular fluid and parotid gland saliva samples in cGVHD patients. In the control group 14.3% of both, four gingival crevicular fluid and four parotid gland saliva samples were positive. Two oral tissue samples of cGVHD patients were positive for HHV6. These results indicate that patients with oral manifestations of cGVHD and healthy individuals present high and similar incidence of HHV6 in blood and oral fluids. These data do not support the importance of HHV6 in oral lesions of cGVHD.
Assuntos
Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 6/patogenicidade , Doenças da Boca/virologia , Adulto , Estudos de Casos e Controles , DNA Viral/análise , Feminino , Líquido do Sulco Gengival/virologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Líquen Plano Bucal/etiologia , Líquen Plano Bucal/virologia , Masculino , Pessoa de Meia-Idade , Doenças da Boca/etiologia , Mucosa Bucal/virologia , Úlceras Orais/etiologia , Úlceras Orais/virologia , Saliva/virologia , Glândulas Salivares Menores/virologiaRESUMO
The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.
Assuntos
Bacteriemia/mortalidade , Resistência a Múltiplos Medicamentos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Brasil/epidemiologia , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Criança , Pré-Escolar , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
AIM: The influence of panel-reactive antibody level (%PRA) on crossmatch results was evaluated among 866 patients on the waiting list for cadaveric renal allografting from January 2001 to August 2005. We evaluated the results for 124 potential donors for a kidney, including 2008 crossmatches. Four hundred eighteen patients were tested against only 1 donor. METHODS: Serum samples were screened for anti-HLA antibodies using immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) PRA kit and the %PRA of the most reactive sample (peak) was used for patient stratification, according to sensitization level. Crossmatches were performed on fresh donor T lymphocytes from peripheral lymph nodes, using classical and anti-human-globulin enhanced complement-dependent cytotoxicity (CDC-T) methods. The tests were performed using peak and current patient sera before and after dithiothreitol treatment. The crossmatch was assumed to be negative when no reactivity was observed in all tests. RESULTS: The incidences of positive crossmatch were as follows: 72.3%, 14.6%, and 7.2%, among patients with PRA >50%, PRA
Assuntos
Teste de Histocompatibilidade/métodos , Isoanticorpos/imunologia , Transplante de Rim/imunologia , Sistema ABO de Grupos Sanguíneos/imunologia , Cadáver , Rejeição de Enxerto/imunologia , Humanos , Linfócitos T/imunologia , Doadores de Tecidos , Listas de EsperaRESUMO
The objective of the study was to evaluate the frequency and clinical characteristics of ocular complications and their risk factors, as well as autologous serum tears (AST) for the treatment of dry eye in these patients. Data from the files of 124 patients who had undergone allogeneic haematopoietic progenitor cell transplantation (HPCT) were evaluated. In addition, 33 HPCT patients were examined and their data were compared with controls. Analysis of tears and AST was performed. Dry eye manifestation occurred in 32% of patients and was positively correlated with age over 27 years (P = 0.05), peripheral blood progenitor cell transplant (P = 0.002), chronic graft-versus-host disease (P = 0.0027), and chronic or acute myeloid leukaemia (P = 0.001). Dry mouth and Schirmer test < 5 mm were predictive factors for dry eye in HPCT patients (P = 0.002 and odds ratio 3.9 and P = 0.007, odds ratio = 5.9, respectively). Microbiological analysis revealed that six of 11 AST samples were contaminated after 30 days of use. The present study supports the role of potential risk factors for ocular complications and key elements to detect alterations in the tear film from HPCT patients. In addition, AST contamination must be considered after longer periods of use.
Assuntos
Síndromes do Olho Seco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Soluções Oftálmicas/uso terapêutico , Soro , Adolescente , Adulto , Fatores Etários , Criança , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/química , Soluções Oftálmicas/isolamento & purificação , Fatores de RiscoRESUMO
Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Cintilografia/métodos , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/lesões , Transplante Homólogo/métodos , Adulto , Feminino , Gálio/metabolismo , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Glândulas Salivares/metabolismo , Glândula Submandibular/metabolismo , Tecnécio/metabolismo , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Xerostomia/etiologia , Xerostomia/metabolismoRESUMO
This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Indução de Remissão , Fatores de Risco , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.
Assuntos
Antígenos CD34/biossíntese , Antineoplásicos/farmacologia , Transfusão de Sangue/métodos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Adolescente , Adulto , Contagem de Células Sanguíneas , Células Sanguíneas , Linhagem Celular Tumoral , Criança , Feminino , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucaférese , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Neutrófilos/metabolismo , Análise de Regressão , Fatores de Tempo , Transplante AutólogoRESUMO
BACKGROUND: The established pathologic criteria for minor salivary gland (MSG) involvement in chronic graft-vs.-host disease (cGVHD) could play a role in monitoring response to therapy. METHODS: We evaluated MSG sequential biopsies during cGVHD therapy in 14 allogeneic bone marrow transplantation (BMT) patients. Nine patients that did not develop GVHD after BMT entered the control group. Biopsies were examined using hematoxylin-eosin, Periodic acid-Schiff (PAS) and leukocyte common antigen staining. RESULTS: A significant loss of PAS+ acinar volume was observed at the diagnosis of cGVHD as much as at the end of treatment when compared with the control group. In the second evaluation, the inflammatory infiltrate was still greater than control group. CONCLUSIONS: The results suggest that persistent xerostomia after cGVHD treatment is because of maintenance of lymphocytic infiltrate and consequent absence of MSG secretory unit recovery. This data may be useful to provide improved insight into the histopathology of this organ involvement.
Assuntos
Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/patologia , Glândulas Salivares Menores/patologia , Xerostomia/etiologia , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Biópsia , Transplante de Medula Óssea/efeitos adversos , Estudos de Casos e Controles , Doença Crônica , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Reação do Ácido Periódico de Schiff , Prednisona/uso terapêuticoRESUMO
Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate. The number of prior transfusions was 0-276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received 15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for 50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.