ABSTRACT
ABSTRACT graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.
RESUMO A doença do enxerto contra hospedeiro (DECH) é uma das principais complicações do transplante de células-tronco Hematopoéticas, acometendo cerca de 50% a 80% dos pacientes. A DECH aguda e suas manifestações clínicas são discutidas neste artigo, bem como a classificação revisada do NIH para diagnóstico e classificação da DECH crônica. A terapêutica para DECH aguda e crônica é um importante campo de discussão uma vez que não há superioridade comprovada para a maioria das terapêuticas utilizadas após o tratamento primário. Assim, esta revisão pretende ser instrumento de consulta para hematologistas transplantadores que lidam com esta complexa complicação do procedimento.
Subject(s)
Humans , Male , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Severity of Illness Index , Acute Disease , Chronic Disease , Risk Factors , Graft vs Host Disease/classificationABSTRACT
Objective To validate the minimal criteria of the histopathologic diagnosis of oral chronic graft-versus-host disease, based on the histopathologic classification of the National Institutes of Health and correlate them with clinical features. Methods Forty-one specimens containing both oral mucosa and salivary glands were analyzed in slides stained with hematoxylin-eosin. The histological specimens were blindly examined by two trained pathologists using criteria recommended for the histopathologic diagnosis of chronic graft-versus-host disease proposed by the National Institutes of Health Consensus. The clinical classification of chronic graft-versus-host disease was correlated with analysis of slides. Results: Our data showed that the epithelium was involved in 39/41 specimens, presenting acanthosis (29/70.7%), exocytosis of lymphocytes (29/70.7%), thickening of basal lamina (29/70.7%), and apoptosis (15/36.6%). Connective tissue presented interstitial inflammatory infiltrate (38/92.7%). Minor salivary glands showed periductal fibrosis (38/92.7%), mixed periductal inflammatory infiltrate (32/78%), ductal ectasia (30/73.2%), lymphocytes around and into acinar units (30/73.2%), and interstitial fibrosis (29/70.7%). The most common clinical manifestations were lichenoid aspect (40/97.6%), complaints of sensitivity to oral feeding (38/92.7%), and dry mouth sensation (36/87.8%). Conclusion This study validated the National Institutes of Health Consensus of minimal histologic criteria for diagnosis of oral chronic graft-versus-host disease and has not found an association between the severity of clinical manifestation and the histopathological stage. .
Objetivo Validar os critérios mínimos de diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica oral, com base em critérios de classificação do National Institutes of Health, e correlacioná-los com as características clínicas. Métodos Quarenta e um espécimes contendo mucosa oral e glândulas salivares foram analisados em lâminas coradas por hematoxilina-eosina. Os espécimes histológicos foram avaliados de forma cega, por dois patologistas calibrados, utilizando os critérios recomendados para diagnóstico histopatológico de doença do enxerto contra hospedeiro crônica propostos pelo Consenso do National Institutes of Health. A classificação clínica da doença do enxerto contra hospedeiro crônica foi correlacionada após a análise das lâminas. Resultados Nossos resultados mostraram que o epitélio estava comprometido em 39/41 espécimes, apresentando acantose (29/70,7%), exocitose de linfócitos (29/70,7%), espessamento da lâmina basal (29/70,7%) e apoptose (15/36,6%). O tecido conjuntivo apresentou infiltrado inflamatório intersticial em 38 (92,7%) casos. Nas glândulas salivares menores, observaram-se fibrose periductal (38/92,7%), infiltrado inflamatório periductal misto (32/78%), ectasia ductal (30/73,2%), linfócitos em torno e migrando para dentro dos ácinos (30/73,2%), e fibrose intersticial (29/70,7%). As manifestações clínicas mais comuns foram mucosa de aspecto liquenoide (40/97,6%), queixa de sensibilidade bucal ao se alimentar (38/92,7%), e sensação de boca seca (36/87,8%). Conclusão Os critérios mínimos para o diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica oral, com base no Consenso do National Institutes of Health, foram ...
Subject(s)
Humans , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Salivary Gland Diseases/pathology , Biopsy , Chronic Disease , Consensus , Graft vs Host Disease/classification , Graft vs Host Disease/complications , Mouth Mucosa/pathology , National Institutes of Health (U.S.) , United StatesABSTRACT
La enfermedad injerto versus huésped (EIVH) es una entidad de frecuente presentación en las personas que son intervenidas con alotrasplantes. Es inducida y mantenida por las células inmunocompetentes del injerto, que atacan los tejidos del huésped; especialmente los epitelios. El diagnóstico de la EIVH es clínico, apoyado en la histopatología, pero esta, por sí misma, no permite diagnosticar la entidad. La primera línea de tratamiento de la EIVH continúan siendo los esteroides sistémicos y ante refractariedad para estos, aparecen nuevas terapéuticas que resultan efectivas en casos reportados en la literatura, sin que aún se hayan podido definir guías de manejo para este tipo de pacientes. Se necesita realizar estudios de terapéutica en pacientes refractarios a esteroides para poder concluir al respecto.
Graft versus host disease is a condition of frequent occurrence in people who are implanted with allogeneic transplants. The diagnosis is clinical, supported by histopathology, but this, by itself does not make a diagnosis. The first line of treatment for this entity are systemic steroids. For the patient refractory to systemic steroids, new therapeutics that could be useful are reported, but not yet defined its use and none were superior to steroids. Studies are needed to define the approach to the patient refractory to steroids.
Subject(s)
Humans , Male , Female , Graft vs Host Disease/classification , Graft vs Host Disease/diagnosis , Graft vs Host Disease/history , Graft vs Host Disease/pathology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/therapy , Epithelium , LymphocytesABSTRACT
BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHODS: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.
Subject(s)
Graft vs Host Disease/classification , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , MentoringABSTRACT
PURPOSE: In this study, we analyzed a cohort of children with chronic graft-versus-host disease (GvHD) according to the NIH consensus classification (NCC) in order to observe whether global assessment at diagnosis correlates with GvHD-specific endpoints. We then studied the clinical course of these patients, specifically with regards to episodes of GvHD exacerbation requiring treatment escalation. MATERIALS AND METHODS: Recipients of either allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) from January 2006 to August 2008 at the Department of Pediatrics, The Catholic University of Korea were evaluated for chronic GvHD, which was diagnosed according to the NCC. The course of chronic GvHD in these patients was then followed. RESULTS: Of 59 evaluable patients, 23 developed chronic GvHD for a cumulative incidence of 39.3%. Upon multivariate analysis, previous acute GvHD (> or =grade II) had a significant impact on chronic GvHD incidence. With a median duration of systemic treatment for chronic GvHD of 501 days, no significant relationship was found between initial global severity of chronic GvHD and either duration of immunosuppressive treatment or final clinical response to treatment. Fifteen patients (65%) experienced at least one episode of chronic GvHD exacerbation during the period of follow-up, with a median of four exacerbations in the subgroup of patients who experienced such events. Lung GvHD resulted in the highest number of exacerbations per diagnosed patient, followed by oral GvHD. CONCLUSION: Analysis of this small cohort indicates that global assessment as proposed by the NCC may have limited correlations with GvHD-specific endpoints, possibly due to the favorable response of children to treatment.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Bone Marrow Transplantation/adverse effects , Chronic Disease , Cohort Studies , Consensus Development Conferences, NIH as Topic , Graft vs Host Disease/classification , Immunosuppressive Agents/administration & dosage , Peripheral Blood Stem Cell Transplantation/adverse effects , Prognosis , Republic of Korea , Risk Factors , United StatesABSTRACT
Debido al incremento en la utilización del trasplante alogénico de médula ósea como terapéutica, es cada vez más frecuente observar la enfermedad injerto contra huésped como una de sus complicaciones de mayor relevancia. Ésta suele ser una causa importante de morbimortalidad en los pacientes trasplantados. Las manifestaciones cutáneas generalmente son las primeras en aparecer, y tanto su forma aguda como crónica presentan una gran variedad clínica. El objetivo de este trabajo es revisar la etiología, las características clínicas e histopatológicas, el diagnóstico y la terapéutica de la enfermedad de injerto contra huésped cutánea.
Subject(s)
Humans , Graft vs Host Disease/classification , Graft vs Host Disease/physiopathology , Graft vs Host Disease/pathology , Graft vs Host Disease/drug therapy , Bone Marrow Transplantation , Glucocorticoids , Immunosuppressive Agents , Photopheresis , Pulse Therapy, Drug , Transplantation, Homologous/adverse effectsABSTRACT
Los pacientes sometidos a trasplante de células hematopoyéticas experimentan un período prolongado de disfunción inmunológica que puede persistir por un año o más, con una afectación tanto de la inmunidad celular como humoral. Esto hace que tengan un riesgo elevado de infecciones en el período postrasplante. Después del acondicionamiento, hay una pérdida de la memoria de inmunidad acumulada durante toda la vida a la exposición a agentes infecciosos, ambientales y vacunaciones. El tratamiento de las infecciones se hace difícil, dado la pobre respuesta inmunitaria presente. Una de las herramientas para limitar el riesgo de infección es el uso de vacunas, aunque su efectividad se ve limitada por la inmunidad disfuncional que caracteriza a este período
Subject(s)
Humans , Hematopoietic Stem Cells/immunology , Graft vs Host Disease/classification , Graft vs Host Disease/physiopathology , Antibody Formation/immunology , Hematopoietic Stem Cell Transplantation , Immunity, Cellular , Transplantation ConditioningABSTRACT
La enfermedad de Injerto contra Huésped (EICH) es una cuadro que se produce en algunos de los pacientes receptores de un trasplante de médula ósea, en el cual los linfocitos T inmunocompetentes del tejido trasplantado reaccionan en contra de los tejidos del receptor (huésped). Se divide en dos grandes grupos: agudo y crónico. Sus manifestaciones clínicas son diversas, dadas por el compromiso variable de piel, hígado, tracto gastrointestinal, entre otros. Las lesiones cutáneas suelen ser el hallazgos más frecuente tanto en la forma aguda como crónica. Dada la existencia de múltiples procesos patológicos que pueden simular una EIDCH, su diagnóstico requiere, además de un alto índice de sospecha, el estudio histológico y el seguimiento cercano de los pacientes. Dado que cada vez son más frecuentes los trasplantes de médula ósea, así como sus manifestaciones más habituales y precoces ocurren en la piel, es muy importante para los dermatólogos estar familiarizados con este cuadro clínico.
Subject(s)
Male , Adult , Humans , Graft vs Host Disease/complications , Graft vs Host Disease/pathology , Skin Diseases/immunology , Bone Marrow Transplantation/adverse effects , Acute Disease , Chronic Disease , Graft vs Host Disease/classification , Graft vs Host Disease/therapyABSTRACT
El trasplante de médula ósea es actualmente un procedimiento de rutina en el tratamiento de tumores sólidos, neoplasias hematológicas, enfermedades adquiridas no malignas y padecimientos congénitos. Este tipo de tratamiento permite remisiones y sobrevidas a largo plazo entre 50 a 90 por ciento de los casos en general y dependiendo del tipo de padecimiento, las condiciones del enfermo y el estadio de enfermedad habitualmente mortales. El conocimiento cada vez más detallado de la biología de las células hematopoyéticas, la posibilidad de recolectarlas de la sangre periférica mediante procedimientos de eféresis y la facilidad de movilizarlas mediante quimioterpia y factores estimulantes de colonias, permite cada vez mejores resultados y hace el trasplante más sencillo. Por otro lado, el establecimiento de rutinas de profilaxis y tratamiento agresivos contra procesos infecciosos, ha permitido el abatimiento de la morbi-mortalidad peritrasplante aún en pacientes con inmunocompromiso grave, secundario a trasplante alogénico de médula ósea y enfermedad de injerto contra huésped