RESUMO
Introducción: Hay poca información actualizada sobre las características clínicas y la gravedad de los pacientes con EPOC que ingresan por una agudización. Nuestro objetivo fue caracterizar a los pacientes que ingresan por agudización de EPOC según la limitación al flujo aéreo: obstrucción leve (Volumen Espiratorio Forzado en el primer segundo [VEF1] ≥ 80%); moderada (VEF1 50 - 79%); grave (VEF1 30 - 49%); o muy grave (VEF1 <3 0%).Métodos: Realizamos un análisis post-hoc del ensayo clínico multicéntrico SLICE (Significance of Pulmonary Embolism in COPD Exacerbations), que reclutó pacientes consecutivos con agudización de EPOC que requirieron ingreso en 18 hospitales españoles en el periodo comprendido entre septiembre de 2014 y julio de 2020.Resultados: Incluimos 737 pacientes, con una edad media (DE) de 70,2 ± 9,9 años, y un predominio de hombres (73,5%). La espirometría clasificó a los pacientes con obstrucción leve, moderada, grave o muy grave en el 8%, 31,5%, 45% y el 15,5%, respectivamente. Al comparar a los pacientes de acuerdo al grado de obstrucción, observamos que los pacientes con mayor obstrucción al flujo aéreo eran más jóvenes (leve: 71,7 ± 8,8, moderada: 72,4 ± 10, grave: 70,2 ± 9,8, muy grave: 66,6 ± 9,2; p < 0,001), presentaban más insuficiencia respiratoria crónica (37,3% vs. 30,2% vs. 44,9% vs. 64,3%; p < 0,001), presentaban más cianosis (5,8% vs. 5,9% vs. 8,5% vs. 15,3%; p < 0,001), presentaron mayor porcentaje de agudizaciones y estaban más taquicárdicos a su llegada al centro hospitalario (92 ± 16 latidos por minuto [lpm] vs. 94 ± 18 vs. 96 ± 18 lpm vs. 99 ± 18 lpm; p < 0,001). Además, la gasometría arterial al ingreso mostraba un pH menor y una pCO2 mayor cuanto más grave era la obstrucción al flujo aéreo (p < 0,001). Conclusión: La gravedad de la obstrucción al flujo aéreo se asocia con la forma de presentación y el resultado de la gasometría arterial del paciente con agudización de EPOC que requiere ingreso hospitalario. (AU)
Introduction: There is little up-to-date information on the clinical characteristics and severity of COPD patients admitted for an exacerbation. Our objective was to characterize patients admitted due to COPD exacerbation according to airflow limitation: mild obstruction (Forced Expiratory Volume in 1 second [FEV1] ≥ 80%); moderate (FEV1 50 - 79%); severe (FEV1 30 - 49%); or very severe (FEV1 <3 0%).Methods: We performed a post-hoc analysis of the multicenter clinical trial SLICE (Significance of Pulmonary Embolism in COPD Exacerbations), which recruited consecutive patients with COPD exacerbation who required admission to 18 Spanish hospitals in the period between September 2014 and July 2020.Results: We included 737 patients, with a mean (SD) age of 70.2 ± 9.9 years, and a predominance of men (73.5%). Spirometry classified patients with mild, moderate, severe, or very severe obstruction in 8%, 31.5%, 45%, and 15.5%, respectively. When comparing the patients according to the degree of obstruction, we observed that the patients with greater airflow obstruction were younger (mild: 71.7 ± 8.8, moderate: 72.4 ± 10, severe: 70.2 ± 9.8, very severe: 66.6 ± 9.2; p < 0.001), had more chronic respiratory failure (37.3% vs. 30.2% vs. 44.9% vs. 64.3%; p < 0.001), had more cyanosis (5.8% vs. 5.9% vs. 8.5% vs. 15.3%; p < 0.001), had a higher percentage of exacerbations and were more tachycardic on arrival at the center hospital (92 ± 16 beats per minute [bpm] vs. 94 ± 18 vs. 96 ± 18 bpm vs. 99 ± 18 bpm; p < 0.001). In addition, arterial blood gases on admission showed a lower pH and a higher pCO2 the more severe the airflow obstruction was (p < 0.001).Conclusion: The severity of the airflow obstruction is associated with the form of presentation and the result of the arterial blood gases of the patient with COPD exacerbation who requires hospital admission. (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença Pulmonar Obstrutiva Crônica , Exacerbação dos Sintomas , Espanha , Hospitalização , EspirometriaRESUMO
Se desconoce el significado pronóstico de las anormalidades pulmonares intersticiales (API) observadas en tomografíacomputarizadas realizadas a pacientes sin sospecha de enfermedad pulmonar intersticial. Por ello, presentamos una revisión de la literatura actual para estudiar su evolución y su manejo.(AU)
The prognostic significance of interstitial lung abnormalities (ILAs) observed on computed tomography performed in pa-tients without suspected interstitial lung disease is unknown. Therefore, we present a review of the current literature to study its evolution and management.(AU)
Assuntos
Humanos , Doenças Pulmonares Intersticiais , Prognóstico , Tomografia Computadorizada por Raios X , Radioterapia , Doenças RespiratóriasRESUMO
Las enfermedades pulmonares intersticiales difusas (EPID) se consideran un grupo heterogéneo de patologías que comparten en su mayoría manifestaciones clínicas, radiológicas y funcionales. El diagnóstico de las EPID se basa en la combinación de información clínica y pruebas funcionales, radiológica mediante la tomografía axial computarizada de alta resolución (TCAR) y/o histológica. Sin embargo, el uso de la ecografía pulmonar en la patología intersticial está poco desarrollada, tanto en el screening como en el seguimiento. Realizamos una revisión de la literatura para determinar la utilidad y las limitaciones de la ecografía en dicha patología (AU)
Diffuse interstitial lung diseases (ILD) are considered a heterogeneous group of pathologies that mostly share clinical, radiological and functional manifestations. The diagnosis of ILD is based on the combination of clinical information and functional tests, radiological by high resolution computed tomography (HRCT) and / or histological. However, the use of lung ultrasound in interstitial pathology is poorly developed, both in screening and in follow-up. We conducted a literature review to determine the usefulness and limitations of ultrasound in this pathology (AU)
Assuntos
Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Ultrassonografia , SeguimentosRESUMO
Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.
Assuntos
Bussulfano/uso terapêutico , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença de Hodgkin/complicações , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Espanha , Análise de Sobrevida , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
BACKGROUND: The most severe form of cutaneous acute graft-versus-host disease (aGVHD), stage IV, is characterized by the appearance of vesicles and blisters. OBJECTIVE: To describe the clinicopathological characteristics and evolution of stage IV cutaneous aGVHD presented in our hospital. METHOD: Retrospective study. The following criteria for inclusion were applied: (i) patients subjected to allogeneic stem cell transplantation between 1st January 1984 and 31st of December 2006; (ii) development of vesicles and/or blisters; (iii) extracutaneous coincidental aGVHD manifestations; and (iv) presence of histopathological features consistent with aGVHD. RESULTS: Fifteen cases (10 females and 5 males) were studied. The mean age was 38.1 years. The lesions appeared after a median interval of 19 days, always following a milder stage of GVHD. Two patterns of clinical evolution were found. Mucosal involvement was observed in nine patients. Nikolsky's sign was positive in eight patients. Nine of the patients had biopsies of the vesiculobullous stage which showed a subepidermal blister with epidermal necrosis and basal vacuolar degeneration. Only two patients survived. CONCLUSION: Stage IV cutaneous aGVHD is a severe and unusual complication after haematopoietic stem cell transplantation. Prognosis is poor with a very high mortality rate, although the cause of death is varied and not strictly linked to the cutaneous disease.
Assuntos
Doença Enxerto-Hospedeiro/patologia , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Nowadays, the chemoradiotherapeutic protocols for Hodgkin's disease (HD) achieve high curability rates. Hemato-oncologists focus on both avoiding medical and psychological sequelae of the treatment and returning patients to a normal life. The quality of life and psychological well-being of Spanish patients who are long-term survivors of HD were studied and compared to the results obtained from healthy controls. Questionnaires on quality of life [European Organization for Research and Treatment of Cancer (EORTC) QLQ30] and psychological status [hospital anxiety and depression (HAD) scale] were mailed to HD patients without active disease and free of second malignancies and were also given to healthy controls. Of 67 selected patients (68.6%), 46 were included in this study. The median follow-up for these 46 patients was of 7.6 years (0.8-22.1) after being diagnosed. Although there were no differences between patients and controls with regard to their global state of health and quality of life (72.9+/-22.7 vs 79.3+/-18.7; p=0.22), patients presented a lower physical function (88.2+/-18.1 vs 96.5+/-9.7; p=0.05) and a worse social operation scale (81.5+/-25.4 vs 96.3+/-13.1; p= 0.0015) together with higher symptoms of dyspnea (8.6+/-14.7 vs 0+/-0; p=0.03) and higher economic difficulties (23.1+/-38.3 vs 0.7+/-4.9; p=0.017) when compared with healthy controls. However, we did not find differences in the scores and the proportion of cases of anxiety and depression between the two groups. The quality of life questionnaire disclosed differences between patients and controls in some functional and symptomatic scales. These differences can be read as a consequence of either the disease itself or the treatment received. However, the results of this controlled pilot study should be confirmed in a larger series of Spanish HD survivors. In the future, these results could be a reference when new therapeutic protocols are designed to reduce the impact on the quality of life of the patients. Socioeconomic support to the patients should also be provided in order to improve their medical care.
Assuntos
Doença de Hodgkin/psicologia , Saúde Mental , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade , Estudos de Casos e Controles , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Espanha , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To assess the efficacy and safety of clinafloxacin as a single agent for the empirical treatment of febrile episodes and bacterial infections in neutropenic cancer patients. METHODS: An open label, active-controlled, randomized, parallel treatment, multicenter study was conducted where clinafloxacin monotherapy was compared to the combination of ceftazidime plus amikacin (plus optional vancomycin or teicoplanin). Four hundred and nineteen patients were randomized to receive either intravenous clinafloxacin 200 mg every 12 h or intravenous ceftazidime (2 g) iv every 8 h plus intravenous amikacin (15 mg/kg) per day in divided doses. All randomized patients were to receive a minimum of 48 h of primary study drug treatment, after which the primary treatment could be modified. Clinical and microbiological responses were evaluated at 7-21 days post-treatment after study treatment and long term (maximum 28 days), in intent-to-treat and modified intent-to-treat populations. RESULTS: Clinafloxacin and ceftazidime-amikacin were statistically equivalent for the 72-h defervescence rate, overall defervescence rate, time to defervescence, clinical success rate, by-pathogen microbiological eradication rate, and survival rate. Clinical cure was achieved in 84% (59/70) of patients who received clinafloxacin monotherapy. There were no significant differences between treatments in rates of adverse events or treatment discontinuation rates due to adverse events. CONCLUSIONS: Clinafloxacin appears to be an appropriate agent for empirical treatment in febrile neutropenic cancer patients.
Assuntos
Amicacina/uso terapêutico , Anti-Infecciosos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Ceftazidima/uso terapêutico , Fluoroquinolonas , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Amicacina/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Anti-Infecciosos/efeitos adversos , Infecções Bacterianas/etiologia , Ceftazidima/efeitos adversos , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada/efeitos adversos , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Teicoplanina/efeitos adversos , Teicoplanina/uso terapêutico , Resultado do Tratamento , Vancomicina/efeitos adversos , Vancomicina/uso terapêuticoRESUMO
El convenio U.C.V.-Corpoamigos ANACO es uno de los seminarios del Programa de Extensión Docencia-Servicio de la Facultad de Odontología que se viene realizando en 16 estados del país. Dicho seminario cuenta con los recursos humanos, materiales y financieros necesarios para una óptima atención a la comunidad, por lo cual es considerado uno de los seminarios más importantes de la facultad de odontología de la UCV. En el siguiente estudio de investigación se tomaron 142 pacientes de ambos sexos con edades comprendidas entre 6 y 10 años (con la pérdida de algunos primeros molares). Los resultados obtenidos muestran una alta prevalencia de pérdida de este molar, lo que nos lleva a enfrentar la problemática presente en las poblaciones rurales por la pérdida del primer molar a edad temprana, cuya situación se agrava por falta de programas preventivos en dichas regiones. Es importante hacer notar la existencia de investigaciones epidemiológicas de este tema en poblaciones rurales como la de Anaco
Assuntos
Humanos , Masculino , Adolescente , Feminino , Serviços de Integração Docente-Assistencial , Dente Molar , Programas Nacionais de Saúde , Perda de Dente/epidemiologia , Assistência Odontológica para Crianças/métodos , Odontologia Comunitária , Dentição Permanente , Estudos Epidemiológicos , Erupção Dentária/fisiologia , Faculdades de Odontologia , Oclusão Dentária Traumática/diagnóstico , Oclusão Dentária Traumática/etiologia , Perda de Dente/etiologia , Projetos de Pesquisa , Mantenedor de Espaço em Ortodontia , VenezuelaRESUMO
BACKGROUND AND OBJECTIVES: There is only limited experience with conditioning regimens based on busulfan for patients with acute lymphoblastic leukemia (ALL). Therefore, the aim of this study was to compare the event-free survival (EFS), transplant-related mortality (TRM) and the probability of relapse (PR) of patients undergoing hematopoietic cell transplantation (HCT) for ALL conditioned with or without total body irradiation (TBI). DESIGN AND METHODS: The study sample consisted of 156 patients conditioned with regimens based on TBI (n=114) or on high doses of oral busulfan (BU) (n=42). Most of the BU group received phenytoin as prophylaxis for seizures. The median follow-up was 6 years. RESULTS: EFS at 6 years was 43% (95% CI 35%-51%) versus 22% (95% CI 10%-34%) in the TBI and BU subsets respectively (p=0.01). TRM at 18 months was 22% and 17% in the BU and TBI groups (p=0.24), respectively. At 3 years actuarial PR was 71% in the BU group and 47% in the TBI group (p=0.01). In the multivariable analysis, a worse EFS was associated with BU, relative risk (RR) 1.7; advanced disease versus 1st and 2nd complete remission (CR) at HCT, RR 2.5; absence of chronic graft-versus-host disease, RR 1.8; development of veno-occlusive disease RR 2.2 and shorter CR duration before transplant. INTERPRETATION AND CONCLUSIONS. TBI was associated with a lower relapse rate and better EFS, even in patients in 1(st )and 2(nd) CR, than schemes based on high doses of busulfan. This suggests that conditioning regimens based on TBI should remain the standard method of preparative regimen for patients with ALL.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Irradiação Corporal Total , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenitoína/administração & dosagem , Resultado do TratamentoRESUMO
This retrospective study has aimed at determining the prevalence, aetiology and clinical evolution of chronic liver disease (CLD) after allogeneic bone marrow transplantation (BMT). A total of 106 patients who had been transplanted in a single institution and who had survived for at least 2 years after BMT were studied. The prevalence of CLD was 57.5% (61/106). In 47.3% of cases more than one aetiopathogenic agent coexisted. The causes of CLD were iron overload (52.4%), chronic hepatitis C (47.5%), chronic graft-versus-host disease (C-GVHD) (37.7%), hepatitis B (6.5%), non-alcoholic steatohepatitis (NASH) (4.9%), autoimmune hepatitis (AIH) (4.9%) and unknown two (3.3%). Twenty-three patients with iron overload underwent venesections which were well tolerated. An improvement in liver function tests (LFTs) was observed in 21 (91%) patients. All six patients with siderosis as the only cause of CLD normalized LFT as well as three patients with HCV infection. Clinical evolution was satisfactory for patients with GVHD, AIH, NASH and hepatitis B. At the last visit 23 patients continued with abnormal LFTs, and 19 of them were infected by the HCV. A sustained biochemical and virologic response was achieved in only one case out of six patients with CHC who received interferon. We have found that CLD is a common complication in long-term BMT survivors. The aetiology is often multifactorial, iron overload, CHC and C-GVHD being the main causes. The CLD followed a rather 'benign' and slow course in our patients as none of them developed symptoms or signs of liver failure and we did not observe an increase in morbidity or mortality in these patients, but a longer follow-up is necessary in HCV infected patients based on the natural history of this infection in other populations.
Assuntos
Transplante de Medula Óssea , Hepatopatias/etiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Alanina Transaminase/sangue , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Hepatite B/etiologia , Hepatite C Crônica/etiologia , Hepatite Autoimune/etiologia , Humanos , Sobrecarga de Ferro/etiologia , Hepatopatias/enzimologia , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Prevalência , Estudos Retrospectivos , Transplante HomólogoRESUMO
Acute renal failure and veno-occlusive disease of the liver are serious complications following stem cell transplantation (SCT) and contribute to the non-relapse mortality associated with this procedure. Endothelins, a family of vasoconstrictor peptides, may be involved in the pathogenesis of a variety of renal and hepatic diseases, including CsA-associated hypertension and the hepatorenal syndrome. In order to study the relevance of endothelins to SCT-related liver and kidney dysfunction, we determined endothelin-1 (ET-1) levels in plasma samples obtained from 65 patients (38 autologous, 27 allogeneic) 7 days before and 7, 14 and 28 days after SCT. A steady increase in plasma ET-1 was observed after SCT (5.36 pg/ml, 95% CI 4.30-6.43 on day +28 vs 3.82 pg/ml, 95% CI 3.21-4.43 on day -7; P = 0.020). No differences in ET-1 levels existed between autologous and allogeneic SCT recipients at any of the time points studied (P = 0.561). In addition, no significant differences were observed among patients with renal dysfunction vs those without (P = 0.187), nor in patient groups with or without hepatic dysfunction (P = 0.075). In conclusion, even though plasma ET-1 levels showed a steady increase following SCT, no correlation could be found with development of SCT-related kidney or liver dysfunction.
Assuntos
Endotelina-1/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcr-abl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs. 45% and 45% vs. 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions.
Assuntos
Antineoplásicos/administração & dosagem , Transplante de Medula Óssea , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Injeções Subcutâneas , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Recidiva , Transplante Homólogo , Resultado do TratamentoRESUMO
PURPOSE: Donor leukocyte infusions (DLI) are useful for treating leukaemic relapse after allogeneic bone marrow transplantation (BMT). We reviewed our experience with eleven patients who received DLI between 1995 and 1997. PATIENTS AND METHODS: The diagnoses prior to DLI were: chronic myeloid leukaemia (CML) in chronic phase (CP) (two patients) or accelerated phase (two patients), acute myeloid leukaemia (AML) (two patients), acute lymphoid leukaemia (ALL) (two patients), and refractory anaemia with excess blasts under transformation (tRAEB) (three patients). The patients received a median of 1.72 x 10(8) CD3+ cells/Kg (range: 0.58 x 10(8) CD3+ cells/Kg). Four patients were infused cryopreserved cells. Six patients received interferon alpha (IFN alpha) concomitantly. RESULTS: Seven patients (four CML, one AML, one ALL, one tRAEB) obtained complete remission (CR). Graft-versus-host disease (GVHD) was observed in all patients with CR and one without response. Marrow hypoplasia or severe bicytopenia occurred in four patients. Of all patients achieving CR, two died after relapsing within 3 months of DLI, while three others died of GVHD. Four patients had no response to DLI or were not evauable. Only two patients--both with CML--are alive 1096 and 374 days after DLI, the former in clinical, cytogenetic and molecular CR, and the latter in second CP after 2 months in CR. CONCLUSIONS: DLI results in CR in most patients with relapsing leukaemia or myelodysplasia after BMT, especially in CML patients. The anti-leukaemia effect is highly correlated with GVHD. This complication and marrow hypoplasia remain major causes of morbidity and mortality of this procedure.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Transfusão de Leucócitos , Adulto , Doadores de Sangue , Feminino , Humanos , Leucaférese , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , RecidivaRESUMO
The objective of this study was to analyze CD34+ cell recovery and T cell depletion (TCD) achieved in CD34+ cell grafts using either immunoadsorption or immunomagnetic methods applied to leukapheresis products from healthy donors. We also wanted to determine the kinetics of engraftment and incidence and severity of graft-versus-host disease (GVHD) after allogeneic transplantation of selected CD34+ cells. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were selected using immunoadsorption (Ceprate SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients, with a median age of 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with immunomagnetic method, respectively. The median number (range) of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (1-9.6). The median number (range) of CD3+ cells administered was 0.4 x 10(6)/kg (0.01-2) using immunoadsorption and 0.14 x 10(6)/kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery >500 and >1000/microl was achieved at a median (range) of 13 days (8-22) and 14 days (9-31), respectively. Platelets recovered to >20000 and >50000/microl at a median (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n = 43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade IV. Chronic GVHD was limited in two cases and extensive in four cases. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of transplant-related mortality was 12.6%, and this figure was 9% at 6 months. In conclusion, with the immunomagnetic procedure, a lower recovery and higher purity of CD34+ cells, and stronger TCD is obtained as compared to immunoadsorption (P = 0.008, P < 0.0001 and P = 0.0002, respectively). Our results also indicate that allogeneic transplantation of selected CD34+ cells is associated with a very rapid engraftment and with a low incidence of severe GVHD.
Assuntos
Antígenos CD34/sangue , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Adolescente , Adulto , Doença Crônica , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Células-Tronco Hematopoéticas/imunologia , Humanos , Separação Imunomagnética , Técnicas de Imunoadsorção , Cinética , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Transplante HomólogoRESUMO
This report summarizes the Spanish experience of 62 cases of allogeneic transplantation of purified CD34+ cells from peripheral blood. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were purified using one of two methods: Ceprate (n = 38), or Isolex 300 (n = 24). Sixty-two patients median age 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11), and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65% and 66% with Ceprate, and 48% and 86% with Isolex, respectively. The median number of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (range 1-9.6). The median number of CD3+ cells administered was 0.4 x 10(6)/kg (range 0.01-2) using Ceprate and 0.14 x 10(6)/kg (range 0.03-2.5) using Isolex. Neutrophil recovery >500 and >1000/microl was achieved at a median of 13 days (range 8-22) and 14 days (range 9-31), respectively. Platelets recovered to >20,000 and >50,000/microl at a median of 13 days (range 0-128) and 18 days (range 0-180), respectively. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD 12% (95% CI, 11-13%).
Assuntos
Doenças Hematológicas/terapia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Antígenos CD34 , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Transplante Homólogo , Resultado do TratamentoRESUMO
Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Doença Crônica , Intervalo Livre de Doença , Feminino , Histocompatibilidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Resultado do TratamentoRESUMO
Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.