ABSTRACT
Mucopolysaccharidosis (MPS) is a metabolic disorder resulting from a deficiency of lysosomal enzymes. It is an autosomal recessive disorder with similar incidences in men and women. Mucopolysaccharidosis type IV A is caused by a deficiency of N-acetylgalactosamine-6-sulfatase, which deficiency is, in turn, caused by alterations in the GALNS gene. It is marked by a short stature, a pigeon chest, frontal bossing, kyphosis, and a flat nasal bridge. Intraorally, macroglossia, hypodontia, dentinogenesis imperfecta, a broad mouth, and an anterior open bite are some of the common features. The present paper reports on a case of MPS in a 5-year-old male patient, along with providing a review of the literature and insight into the oral manifestations related to MPS IV A, also called Morquio A syndrome, and its dental treatment. It aims to highlight the clinical recommendations for oral health care in such cases during different phases of MPS IV A treatment.
Subject(s)
Chondroitinsulfatases , Mucopolysaccharidosis IV , Male , Humans , Child , Female , Child, Preschool , Mucopolysaccharidosis IV/genetics , Mucopolysaccharidosis IV/therapy , Chondroitinsulfatases/genetics , Chondroitinsulfatases/metabolism , Delivery of Health CareABSTRACT
Villitis of unknown etiology (VUE) is an inflammatory disease characterized by the infiltration of maternal CD8 +T cells into the placental villi. Although the pathogenesis of VUE is still debated, dysregulation of the immune system appears to be an important factor in the development of the disease. Interaction of maternal T cells with the fetal antigens seems to be the trigger for the VUE onset. In this context, graft vs host disease (GVHD) and allographic rejection seem to share similarities in the VUE immunopathological mechanism, especially those related to immunoregulation. In this review, we compared the immunological characteristics of VUE with allograft rejection, and GVHD favoring a better knowledge of VUE pathogenesis that may contribute to VUE therapeutics strategies in the future.
Subject(s)
Chorioamnionitis , Graft vs Host Disease , Placenta Diseases , Pregnancy , Female , Humans , Placenta/pathology , Placenta Diseases/pathology , Chorioamnionitis/pathology , Chorionic Villi/pathology , Graft vs Host Disease/complications , Graft vs Host Disease/pathologyABSTRACT
INTRODUCTION: Although extracorporeal photopheresis (ECP) is a promising second-line therapy in the treatment of chronic graft-versus-host disease (cGVHD), its use is limited by its high cost. This study aims to describe the clinical evolution of patients who underwent ECP therapy for cGVHD and to perform an economic analysis of the therapy METHODS: This was a case series between 2016 and 2020 describing the clinical response to ECP and a micro-cost analysis of the therapy using time-driven activity-based costing. RESULTS: Six patients underwent ECP for corticosteroid-dependent cGVHD The cost per ECP session is 14,960.90 Brazilian reais (BRL), which primarily consists of the ECP kit with an activator (82.78%), followed by the hospital's physical structure (14.66%), human resources (2.48%) and exams/inputs (0.08%). The number of sessions performed ranged from 2 to 42. The total cost of the therapy per patient ranged from BRL 30,000 to 500,000. CONCLUSION: The response of the patient with cGVHD to treatment with ECP was variable. These micro-costing results can be used to develop remuneration and cost control strategies in hematopoietic stem cell transplantation programs, as well as in further economic studies.
ABSTRACT
Abstract Introduction Although extracorporeal photopheresis (ECP) is a promising second-line therapy in the treatment of chronic graft-versus-host disease (cGVHD), its use is limited by its high cost. This study aims to describe the clinical evolution of patients who underwent ECP therapy for cGVHD and to perform an economic analysis of the therapy Methods This was a case series between 2016 and 2020 describing the clinical response to ECP and a micro-cost analysis of the therapy using time-driven activity-based costing. Results Six patients underwent ECP for corticosteroid-dependent cGVHD The cost per ECP session is 14,960.90 Brazilian reais (BRL), which primarily consists of the ECP kit with an activator (82.78%), followed by the hospital's physical structure (14.66%), human resources (2.48%) and exams/inputs (0.08%). The number of sessions performed ranged from 2 to 42. The total cost of the therapy per patient ranged from BRL 30,000 to 500,000. Conclusion The response of the patient with cGVHD to treatment with ECP was variable. These micro-costing results can be used to develop remuneration and cost control strategies in hematopoietic stem cell transplantation programs, as well as in further economic studies.
Subject(s)
Humans , Photopheresis , Graft vs Host Disease , Health Evaluation , Costs and Cost AnalysisABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment for many diseases; however, it can induce complications such as Oral Mucositis (OM) and Graft-versus- Host Disease (GVHD). The neutrophil-lymphocyte ratio (NLR) is a peripheral biomarker of systemic inflammation and an independent prognostic factor for several inflammatory diseases. Aim: This study aimed to evaluate the association of NLR with OM and GVHD in patients undergoing allogeneic HSCT. Methods: Patients who underwent allogeneic HSCT at the Bone Marrow Transplant Service of the Hospital de Clínicas Complex of the Federal University of Paraná were included in the study. Socio-demographic data and blood counts were collected from patients' medical records. The NLR was calculated and associated with OM and GVHD. Results: 45 patients were included in the study. Although NLR was higher in patients with OM and oral GVHD, no statistical difference was observed, and no relationship between OM and GVHD with NLR could be stated. Conclusion: Although both OM and GVHD are associated with an inflammatory response as well as the immune system, it was not associated with NLR. Further investigation considering other variables related to HSCT might find possible associations, as it could favor patient management and prevention
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Stomatitis , Lymphocytes , Hematopoietic Stem Cell Transplantation , Graft vs Host Disease , NeutrophilsABSTRACT
BACKGROUND: The incidence of most hematologic malignancies increases with age. Hematopoietic stem cell transplantation (HSCT) provides a potentially life-prolonging or curative option for many patients in this scenario. Limited data assessed from computed tomography (CT) images are available on muscle mass and density outcomes after HSCT. We evaluate the influence of body composition on morbidity and mortality in older adults undergoing HSCT. METHODS: Retrospective longitudinal study conducted with 50 patients ≥ 60 years old undergoing HSCT. Body composition was assessed by chest CT (CCT), and treatment-related mortality, graft-vs-host disease (GVHD), neutrophil grafting, and overall survival were analyzed. RESULTS: 148 HSCT patients were evaluated; 50 patients were eligible: 60% with autologous and 40% with allogeneic transplantation. Body mass index in patients was (female: 26.9 ± 4.7 kg/m2 ; male: 30.1 ± 4.9 kg/m2 ) - autologous and, (female: 24.3 ± 5.1 kg/m2 ; male: 26.4 ± 2.0 kg/m2 ) - allogeneic. In the autologous group, we found a positive association between age and death risk, with 63.5% increased risk of death (P = 0.006), and also Karnofsky Performance Score, with a 11.9% decrease in death risk (P < 0.001). A negative association between muscle radiodensity and death risk was observed in patients who received an allogeneic transplantation, with a risk decrease of 20.1% (P = 0.032). We found a positive association between the fourth thoracic vertebra muscle area and radiodensity and risk of acute GVHD (P = 0.028). CONCLUSION: Body composition assessed by CCT showed the importance of radiodensity for better prognosis.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Male , Female , Aged , Middle Aged , Graft vs Host Disease/diagnostic imaging , Graft vs Host Disease/etiology , Retrospective Studies , Longitudinal Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Body Composition , Tomography, X-Ray Computed , Tomography/adverse effectsABSTRACT
Objetivo: Elucidar quais as formas mais adequadas de se proceder para que haja um efetivo diagnóstico da Doença Enxerto-Contra-Hospedeiro pelo cirurgião-dentista. Revisão de literatura: A Doença Enxerto Contra Hospedeiro acomete diversos pacientes que realizam transplante de células tronco hematopoiéticas. Os sinais clínicos muitas vezes são manifestados apenas na cavidade bucal e, por isso, é importante que o cirurgião-dentista tenha conhecimento. Esta patologia é proveniente de uma complicação do TCTH (Transplante de Células Tronco Hematopoiéticas) alogênico, onde ocorre uma resposta de ativação de linfócitos T do doador e um reconhecimento de antígenos contra o receptor. Discussão: As alterações mais evidentes são lesões ulceradas, estrias brancas, mucocele, leucoedema, lesões bolhosas, ardência, dor e xerostomia. Estes aspectos tendem a corresponder a um diagnóstico de lesões malignas, síndrome de Sjogren, lúpus e líquen plano. A biópsia é fundamental para o diagnóstico, assim como para graduar a severidade da Doença Enxerto Contra Hospedeiro. Conclusão: Caso o cirurgião-dentista identifique algum dos sinais, deverá alertar à equipe médica do paciente para iniciar o tratamento e evitar a recidiva da doença original.
Aim: elucidate which are the most appropriate ways to proceed so that there is an effective diagnosis of Graft--versus-Host Disease by the dentist. Literature review: Graft-versus-host disease affects several patients who undergo hematopoietic stem cell transplantation. Clinical signs are often manifested in the oral cavity only, rea-son why it is important the dentist to be aware of them. This pathology is caused by a complication of allogeneic HSCT, in which there is an activation response of donor T lymphocytes and a recognition of antigens against the recipient. Discussion: The most evident changes are ulcerated lesions, white streaks, mucocele, leukedema, bullous lesions, burning, pain and Xerostomia. These aspects tend to correspond to a diagnosis of malignant lesions, Sjogren's syndrome, lupus and lichen planus. A biopsy is essential for diagnosis as well as for grading the severity of Graft versus Host Disease. Conclusion: If the dental surgeon identifies any of the mentioned signs, he must alert the patient's medical team to start treatment to prevent the recurrence of the original disease.
Subject(s)
Oral Manifestations , Dentistry , Graft vs Host Disease/diagnosisABSTRACT
Graft versus host disease is a serious complication that occurs following bone marrow transplant with significant morbidity and mortality. The gold standard to diagnose gastrointestinal graft versus host disease is upper and lower gastrointestinal endoscopy with histological validation. The development of intramural duodenal hematoma is a rare complication associated with this procedure. We present two cases of intramural duodenal haematoma after duodenal biopsies in bone marrow transplant patients that presented clinically with severe abdominal pain and intestinal bleeding. In both cases, CT scans confirmed the diagnosis and they were treated conservatively with favorable outcomes. Final diagnosis of gastrointestinal graft versus host disease was based on the colonic samples with normal duodenal histoarchitecture, which could lead to avoiding duodenal samples in future patients in order to prevent this serious complication and thus diminish morbidity.
La enfermedad de injerto contra huésped es una complicación grave que se presenta después del trasplante de médula ósea, con morbilidad y mortalidad elevadas. El patrón de oro para evaluar su compromiso gastrointestinal es la endoscopia digestiva alta y baja con toma de biopsia. El desarrollo de hematoma duodenal intramural es una complicación poco frecuente asociada con este procedimiento. Se presentan dos casos de hematoma duodenal intramural posendoscopia en pacientes con trasplante y sospecha de enfermedad injerto contra huésped que presentaron un cuadro agudo de dolor abdominal y sangrado intestinal. El diagnóstico se realizó por tomografía y recibieron tratamiento conservador, con un resultado favorable. En ambos casos, el diagnóstico de enfermedad injerto contra huésped gastrointestinal se hizo a través de las biopsias colónicas con histología duodenal normal, lo que sugiere evitar la toma de muestras duodenales para prevenir esta grave complicación en pacientes de alto riesgo y, de este modo, disminuir la morbilidad.
Subject(s)
Duodenal Diseases , Graft vs Host Disease , Child , Duodenal Diseases/diagnosis , Duodenal Diseases/etiology , Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Hematoma/diagnosis , Hematoma/etiology , HumansABSTRACT
BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children. OBJECTIVE: To describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP. MATERIAL AND METHODS: We included all pediatric patients with acute or chronic GVHD treated with ECP by the dermatology department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response. RESULTS: We evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period. CONCLUSION: ECP is a good treatment option for pediatric patients with acute or chronic GVHD.
ABSTRACT
La enfermedad de injerto contra huésped es una complicación grave que se presenta después del trasplante de médula ósea, con morbilidad y mortalidad elevadas. El patrón de oro para evaluar su compromiso gastrointestinal es la endoscopia digestiva alta y baja con toma de biopsia. El desarrollo de hematoma duodenal intramural es una complicación poco frecuente asociada con este procedimiento .Se presentan dos casos de hematoma duodenal intramural posendoscopia en pacientes con trasplante y sospecha de enfermedad injerto contra huésped que presentaron un cuadro agudo de dolor abdominal y sangrado intestinal. El diagnóstico se realizó por tomografía y recibieron tratamiento conservador, con un resultado favorable. En ambos casos, el diagnóstico de enfermedad injerto contra huésped gastrointestinal se hizo a través de las biopsias colónicas con histología duodenal normal, lo que sugiere evitar la toma de muestras duodenales para prevenir esta grave complicación en pacientes de alto riesgo y, de este modo, disminuir la morbilidad.
Graft versus host disease is a serious complication that occurs following bone marrow transplant with significant morbidity and mortality. The gold standard to diagnose gastrointestinal graft versus host disease is upper and lower gastrointestinal endoscopy with histological validation. The development of intramural duodenal hematoma is a rare complication associated with this procedure. We present two cases of intramural duodenal haematoma after duodenal biopsies in bone marrow transplant patients that presented clinically with severe abdominal pain and intestinal bleeding. In both cases, CT scans confirmed the diagnosis and they were treated conservatively with favorable outcomes.Final diagnosis of gastrointestinal graft versus host disease was based on the colonic samples with normal duodenal histoarchitecture, which could lead to avoiding duodenal samples in future patients in order to prevent this serious complication and thus diminish morbidity.
Subject(s)
Humans , Male , Infant , Child , Duodenal Diseases/diagnosis , Duodenal Diseases/etiology , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Endoscopy, Gastrointestinal , Hematoma/diagnosis , Hematoma/etiology , Gastrointestinal HemorrhageABSTRACT
Introducción: Las quimiocinas son proteínas secretadas con tamaño en el rango de 8-10 kDa, con numerosas funciones en la fisiología normal y patológica. El término deriva de las palabras citocinas quimiotácticas, que refleja su importante participación en la quimioatracción de leucocitos. Sin embargo, las evidencias muestran que las quimiocinas tienen muchas otras funciones como la comunicación intercelular, la activación celular y la regulación del ciclo celular. Objetivo: Analizar los conocimientos actuales sobre las quimiocinas y sus receptores, y la significación clínica de estas en la medicina transfusional y el trasplante. Métodos: Se realizó revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se efectuó análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: La transcripción de la mayoría de los genes de quimiocinas es inducible y se produce en respuesta a estímulos celulares específicos. Las quimiocinas son importantes en la movilización de células progenitoras hematopoyéticas para el trasplante y localización de células progenitoras hematopoyéticas trasplantadas. En los modelos de incompatibilidad ABO, las quimiocinas CXC y CC se producen en niveles elevados. Conclusiones: Muchas son las oportunidades de futuras investigaciones sobre las quimiocinas en la medicina transfusional por la considerable redundancia y superposición en la función biológica de estas moléculas y sus receptores. Son solo una parte de un proceso mucho más grande y complejo dentro de la red de citoquinas y otras moléculas del sistema inmune(AU)
Introduction: Chemokines are secreted proteins with size in the range of 8-10 kDa, with numerous functions in normal and pathological physiology. The term derives from the words chemotactic cytokines, reflecting its important role in the chemoattraction of leukocytes. However, the evidence shows that chemokines have many other functions such as intercellular communication, cell activation and cell cycle regulation. Objetive: To present current knowledge about chemokines and their receptors, and the clinical significance of these in transfusion medicine and transplantation. Method: A review of the literature was made, in English and Spanish, through the PubMed website and the Google academic search engine of articles published in the last 10 years. An analysis and summary of the revised bibliography was made. Developing: The transcription of most of the chemokine genes is inducible and occurs in response to specific cellular stimuli. Chemokines play an important role in the mobilization of hematopoietic progenitor cells for the transplantation and localization of transplanted hematopoietic progenitor cells. In the ABO incompatibility models, the CXC and CC chemokines are produced at high levels. Conclusions: There are many opportunities for future research on chemokines in transfusion medicine due to their considerable redundancy and superposition in the biological function of these molecules and their receptors. They are just one part of a much larger and more complex process within the network of cytokines and other molecules of the immune system(AU)
Subject(s)
Humans , Cytokines , Chemokines , Transfusion Medicine , Immune SystemABSTRACT
BACKGROUND: Extracorporeal photopheresis (ECP) is an immunomodulatory therapy used to treat graft-vs-host disease (GVHD) in adults and children. Few studies have examined its use in children. OBJECTIVE: To describe demographic characteristics, clinical response, adverse effects, and outcomes in a series of pediatric patients with acute or chronic GVHD treated with ECP. MATERIAL AND METHODS: We included all pediatric patients with acute or chronic GVHD treated with ECP by the Dermatology Department of Hospital Italiano de Buenos Aires between January 2012 and December 2018. We used the UVAR-XTS™ system (2 patients) and the CELLEX system (7 patients). Patients with acute GVHD received 2 sessions a week and were reassessed at 1 month, while those with chronic GVHD received 2 sessions every 2 weeks and were reassessed at 3 months. Treatment duration in both scenarios varied according to response. RESULTS: We evaluated 9 pediatric patients with corticosteroid-refractory, -dependent, and/or -resistant GVHD treated with ECP. Seven responded to treatment and 2 did not. Response was complete in 1 of the 9 patients with skin involvement and partial in 7. Complete response rates for the other sites of involvement were 60% (3/5) for the liver, 50% (1/2) for the gastrointestinal system, and 80% (4/5) for mucous membranes. Two patients died during the study period. CONCLUSION: ECP is a good treatment option for pediatric patients with acute or chronic GVHD.
ABSTRACT
ABSTRACT Objective The aim of this study was to evaluate patients with complete response of oral chronic graft-versus-host disease to immunosuppressive treatment. Methods A total of 29 patients submitted to allogeneic hematopoietic stem cell transplantation, with oral chronic graft-versus-host disease, were enrolled in this retrospective study, from September 2012 to February 2018. Patients were treated with combined topical dexamethasone solution and topical tacrolimus ointment, combined topical dexamethasone and topical tacrolimus, systemic immunosuppressive medication, and topical dexamethasone only. Results The mean time of complete response of lichenoid lesions, erythema, and ulcers using dexamethasone and systemic immunosuppressive medication was of 105, 42 and 42 days, respectively (p=0.013).When we associated dexamethasone, tacrolimus and systemic immunosuppressive medication, the mean time of complete response of lichenoid lesions, erythema and ulcers was of 91,84 and 77 days (p=0.011). When dexamethasone was used alone, the mean time of complete response of lichenoid lesions, erythema and ulcers was 182, 140, 21 days, respectively (p=0.042). Conclusion Our study shows that lichenoid lesions require more time to heal. Notably, lichenoid lesions tend to respond better to dexamethasone combined with tacrolimus and systemic immunosuppressive medication, whereas erythema and ulcers respond better to dexamethasone combined with systemic immunosuppressive medication and dexamethasone only, respectively.
RESUMO Objetivo Avaliar os pacientes com resposta completa da doença do enxerto contra hospedeiro crônica oral ao tratamento com imunossupressor. Métodos Vinte e nove pacientes submetidos ao transplante alogênico de células tronco hematopoiéticas, com doença do enxerto contra hospedeiro crônica oral, foram incluídos neste estudo retrospectivo, de setembro de 2012 a fevereiro de 2018. Os pacientes foram tratados com dexametasona para bochecho associada ao tacrolimo pomada, dexametasona para bochecho associada ao tacrolimo tópico, tratamento imunossupressor sistêmico, e dexametasona tópica apenas. Resultados O tempo médio para resposta completa das lesões liquenoides, eritema e ulcerações usando dexametasona e imunossupressor sistêmico foi de 105, 42 e 42 dias, respectivamente (p=0,013). Quando a dexametasona estava associada ao tacrolimo e a medicação imunossupressora sistêmica, o tempo médio para resposta completa das lesões liquenóides, eritema e ulcerações foi de 91, 84 e 77 dias (p=0,011). Quando foi utilizada apenas dexametasona, o tempo médio para resposta completa das lesões liquenoides, eritema e ulcerações foi de 182, 140 e 21 dias, respectivamente (p=0,042). Conclusão Nosso estudo mostra que as lesões liquenoides requerem mais tempo para cicatrização completa. É notável que as lesões liquenoides tendem a responder melhor ao tratamento da dexametasona combinada com o tacrolimo e o imunossupressor sistêmico. Já o eritema e as ulcerações respondem melhor à dexametasona combinada com medicação imunossupressora sistêmica, e dexametasona apenas, respectivamente.
Subject(s)
Humans , Graft vs Host Disease/drug therapy , Mouth Diseases , Chronic Disease , Retrospective Studies , Tacrolimus , Immunosuppressive AgentsABSTRACT
El trasplante de médula ósea es una terapia potencialmente curativa para múltiples enfermedades; el alogénico es el más indicado en leucemias. La enfermedad injerto versus huésped (EIVH) constituye la principal complicación del trasplante de médula ósea alogénico. Tanto en la EIVH aguda como crónica, la piel es el órgano más frecuentemente comprometido. El objetivo fue analizar las manifestaciones cutáneas de esta entidad. Trabajo retrospectivo y descriptivo, que incluyó a 59 pacientes trasplantados de edades entre 0 y 20 años. En 50 casos, se realizó trasplante de médula ósea alogénico. Veinticinco pacientes desarrollaron EIVH (17, la forma aguda, y 8, la forma crónica), y 24 tuvieron compromiso cutáneo. En concordancia con lo comunicado se encontró que las manifestaciones cutáneas fueron la manifestación clínica más común de EIVH. El hallazgo principal en EIVH aguda en nuestra serie fue el rash eritematoso maculopapular y, en EIVH crónica, las lesiones escleróticas símil morf
Bone marrow transplant is a potentially curative therapy for several diseases, and allogeneic bone marrow transplant is the most commonly indicated type for leukemias. Graft versus host disease (GVHD) is the main complication of allogeneic bone marrow transplant. In both acute and chronic GVHD, the skin is the most frequently involved organ. The objective of this study was to analyze cutaneous manifestations of this disease. Retrospective and descriptive study that included 59 transplanted patients aged 0 to 20 years. In 50 cases allogeneic bone marrow transplant was performed. Twenty-five patients developed GVHD (17 acute disease and 8 chronic disease) and 24 of them had cutaneous involvement. According to the literature, skin compromise was the commonest clinical manifestation of GVHD. Main finding in acute GVHD in our series was the erythematous maculopapular rash, while in chronic GVHD they were sclerotic lesions resembling morphe
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Graft vs Host Disease/diagnosis , Skin Manifestations , Transplantation, Homologous , Leukemia , Epidemiology, Descriptive , Retrospective Studies , Bone Marrow Transplantation , ExanthemaABSTRACT
Bone marrow transplant is a potentially curative therapy for several diseases, and allogeneic bone marrow transplant is the most commonly indicated type for leukemias. Graft versus host disease (GVHD) is the main complication of allogeneic bone marrow transplant. In both acute and chronic GVHD, the skin is the most frequently involved organ. The objective of this study was to analyze cutaneous manifestations of this disease. Retrospective and descriptive study that included 59 transplanted patients aged 0 to 20 years. In 50 cases allogeneic bone marrow transplant was performed. Twenty-five patients developed GVHD (17 acute disease and 8 chronic disease) and 24 of them had cutaneous involvement. According to the literature, skin compromise was the commonest clinical manifestation of GVHD. Main finding in acute GVHD in our series was the erythematous maculopapular rash, while in chronic GVHD they were sclerotic lesions resembling morphea.
El trasplante de médula ósea es una terapia potencialmente curativa para múltiples enfermedades; el alogénico es el más indicado en leucemias. La enfermedad injerto versus huésped (EIVH) constituye la principal complicación del trasplante de médula ósea alogénico. Tanto en la EIVH aguda como crónica, la piel es el órgano más frecuentemente comprometido. El objetivo fue analizar las manifestaciones cutáneas de esta entidad. Trabajo retrospectivo y descriptivo, que incluyó a 59 pacientes trasplantados de edades entre 0 y 20 años. En 50 casos, se realizó trasplante de médula ósea alogénico. Veinticinco pacientes desarrollaron EIVH (17, la forma aguda, y 8, la forma crónica), y 24 tuvieron compromiso cutáneo. En concordancia con lo comunicado se encontró que las manifestaciones cutáneas fueron la manifestación clínica más común de EIVH. El hallazgo principal en EIVH aguda en nuestra serie fue el rash eritematoso maculopapular y, en EIVH crónica, las lesiones escleróticas símil morfea.
Subject(s)
Bone Marrow Transplantation/adverse effects , Graft vs Host Disease/complications , Skin Diseases/etiology , Acute Disease , Adolescent , Bone Marrow Transplantation/methods , Child , Child, Preschool , Chronic Disease , Female , Graft vs Host Disease/epidemiology , Humans , Leukemia/therapy , Male , Retrospective Studies , Skin Diseases/epidemiology , Skin Diseases/pathology , Transplantation, Homologous , Young AdultABSTRACT
BACKGROUND: There are no pathognomonic histopathological features to distinguish acute graft-vs-host disease (aGVHD) from skin drug reactions (SDRs) in pediatric patients with multiple drug regimens that have received blood transfusions and/or transplants. We aimed to determine if the addition of apoptosis markers is helpful to distinguish aGVHD from SDRs in these patients. METHODS: Skin biopsy specimens from patients with a clinical diagnosis of aGVHD or SDRs were evaluated for the presence of apoptotic bodies, satellitosis, interface damage, vasculitis, and inflammatory infiltrate on H&E stain. Information was completed with apoptotic markers (transferase-mediated dUTP nick end-labeling [TUNEL], bcl-2, and caspase-3). RESULTS: The skin biopsy specimens of 32 patients with aGVHD and 11 with SDRs were included for study. Only the number of apoptotic keratinocytes per 10 high-power fields (hpf) showed a significant difference between both groups (P = 0.02); the presence of ≥4 apoptotic keratinocytes per 10 hpf was identified as the optimal cut-off point to discriminate aGVHD from SDRs. No SDRs cases had follicular apoptotic cells. TUNEL, bcl-2, and caspase-3 determination showed no difference between both groups. CONCLUSIONS: The presence of ≥4 apoptotic keratinocytes per 10 hpf (in aGVHD) and the absence of follicular apoptotic cells (in SDRs) might be a useful marker to distinguish between them.
Subject(s)
Apoptosis/immunology , Drug Hypersensitivity/pathology , Graft vs Host Disease/pathology , Skin/pathology , Acute Disease , Adolescent , Case-Control Studies , Caspase 3/metabolism , Child , Child, Preschool , Drug Hypersensitivity/immunology , Early Diagnosis , Female , Graft vs Host Disease/immunology , Humans , Infant , Keratinocytes/pathology , Male , Proto-Oncogene Proteins c-bcl-2/metabolism , Retrospective StudiesABSTRACT
OBJECTIVES: To analyse clinical outcomes comparing two age groups of patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to identify risk factors associated with older patients' mortality. METHODS: In this retrospective study, the medical charts of all consecutive patients admitted in one hospital for allo-HSCT were reviewed. Overall survival (OS) and other outcomes were compared between patients aged up to 55 years (YG) and older than 55 (EG). RESULTS: From January 2007 to August 2014, 111 adult patients were admitted for allo-HSCT and were included 75 in the YG and 36 in the EG group. The OS rate at D+ 100 was 84% for YG individuals in contrast to 75% in the EG (p = 0.01), and 71% vs. 50% at one year after HSCT (p = 0.01) respectively. Therapy-related mortality (TRM) rates for the YG and EG were, respectively, 14% vs. 17% (p = 0.04) at D+ 100 and 17% vs. 32% (p = 0.04) at one year. Haploidentical donor type and active disease status significantly increased mortality risk in the EG (hazard ratio 2.42; p = 0.018; and 2.04; p = 0.033). CONCLUSION: YG and EG have similar TRM rates early after allo-HSCT, but the elderly had higher TRM during the critical period from 100 days to one year.
Subject(s)
Graft vs Host Disease/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/mortality , Mortality , Neoplasm Recurrence, Local/mortality , Adolescent , Adult , Age Factors , Aged , Brazil/epidemiology , Female , Haplotypes , Hematologic Neoplasms/mortality , Humans , Intensive Care Units/statistics & numerical data , Length of Stay , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Neoplasm Recurrence, Local/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Proportional Hazards Models , Renal Replacement Therapy/statistics & numerical data , Retrospective Studies , Risk Factors , Survival Rate , Tissue Donors , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
The allogeneic hematopoietic stem cell transplantation procedure-the only curative therapy for many types of hematological cancers-is increasing, and graft vs. host disease (GVHD) is the main cause of morbidity and mortality after transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of information about the chronic form (cGVHD). Using nuclear magnetic resonance (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass spectrometry, this study prospectively evaluated the serum metabolome of 18 Brazilian patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT). We identified and quantified 63 metabolites and performed the metabolomic profile on day -10, day 0, day +10 and day +100, in reference to day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms at sampling times. From 18 patients analyzed, 6 developed cGVHD. The branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The area under receiver operating characteristics (ROC) curves was higher than 0.79. BCAA findings were validated by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, cystine findings were not statistically significant in this patient set. Our results highlight the importance of multi-temporal and multivariate biomarker panels for predicting and understanding cGVHD.
ABSTRACT
OBJECTIVES: To investigate effects and outcome of hematopoietic stem cell transplantation (HSCT) on sclerosing cholangitis, in pediatric patients with different primary immunodeficiencies (PIDs). STUDY DESIGN: From databases in 2 tertiary centers for immunodeficiencies and liver disease, we have identified children with PIDs and sclerosing cholangitis, who have paired clinical, radiologic, and histologic information before and after HSCT and studied their clinical progress and outcome. RESULTS: Seven of 13 children (53.8%) died at a median interval of 4 months (range, 3 months-5 years) after HSCT. However, 6 surviving children (46.2%) with different PIDs and less severe cholangiopathies showed an improvement in markers of liver injury within months of successful unrelated reduced intensity conditioning HSCT. The repeated native liver biopsy, performed in 4 patients at a median of 96 (range, 4-144) months post-HSCT, showed a considerable improvement. Biochemical markers of liver function in the survivors completely normalized after a median of 13 months (range, 2-48). All patients continue to have a mildly dilated extrahepatic biliary system on ultrasonography with no intrahepatic ductal changes on magnetic resonance cholangiography after a follow-up of median 18 years (range, 2-20). CONCLUSIONS: Effective HSCT has the potential to improve biochemical and histologic features of cholangiopathy in children with PIDs, presumably by clearance of chronic infection following establishment of immune competence. However, careful patient selection is critical as advanced liver injury is often associated with serious complications and mortality.
Subject(s)
Cause of Death , Cholangitis, Sclerosing/therapy , Hematopoietic Stem Cell Transplantation/methods , Primary Immunodeficiency Diseases/epidemiology , Primary Immunodeficiency Diseases/therapy , Age Factors , Biopsy, Needle , Child, Preschool , Cholangiopancreatography, Endoscopic Retrograde/methods , Cholangitis, Sclerosing/diagnostic imaging , Cholangitis, Sclerosing/epidemiology , Cholangitis, Sclerosing/pathology , Chronic Disease , Cohort Studies , Databases, Factual , Disease Progression , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation/mortality , Hospitals, Pediatric , Humans , Immunohistochemistry , Infant , Male , Primary Immunodeficiency Diseases/diagnosis , Prognosis , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , Survival Analysis , Treatment Outcome , United KingdomABSTRACT
Resumo Doença do Enxerto-versus-hospedeiro (do inglês Graft-versus-Host Disease - GVHD) é uma complicação importante e com altas taxas de morbidade e mortalidade nos pacientes submetidos ao transplante alogênico de células-tronco hematopoiéticas. O acometimento ocular, denominado GVHD ocular, pode acometer todas as estruturas dos olhos, porém a unidade lacrimal (glândulas lacrimais e superfície ocular) é o principal alvo da resposta inflamatória mediada por células T doadas. O desenvolvimento de doença do olho seco grave é a principal manifestação clínica ocular, e a associação de diversas opções terapêuticas se faz necessário. O objetivo desta revisão é descrever as manifestações clínicas, os critérios diagnósticos, o impacto na qualidade de vida, o tratamento atual e as perspectivas desta doença, que precisa de um acompanhamento multidisciplinar.
Abstract Graft-versus-host Disease (GVHD) is a major complication with high morbidity and mortality rates on patients undergoing hematopoietic stem cell transplantation. The ocular involvement, named ocular GVHD, may affect all structures of the eyes, but the lacrimal unit (lacrimal glands and ocular surface) is the main target of the inflammatory response mediated by the donor T cells. The development of dry eye disease is the main clinical ocular manifestation, and the association of a variety of therapeutics options is necessary. The aim of the review is to describe the clinical manifestations, diagnostic criteria, impact in quality of life, the current treatment and future perspectives of this disease that demands a multidisciplinary follow-up.