Research Progress on Risk Factors and Intervention Measures for Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation --Review / 中国实验血液学杂志

Prolonged thrombocytopenia (PT) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of about 5%-37%, which is closely related to the poor prognosis of patients. Previous studies have shown that transplantation type, CD34+ cell number, pretreatment regimen, acute graft-versus-host disease, virus infection, pre-transplantation serum ferritin level and donor specific antibodies can affect platelet implantation after transplantation. Identifying the risk factors of PT is helpful to early identify high-risk patients and take targeted preventive measures according to different risk factors to reduce the incidence of PT, reduce the risk of bleeding and improve the prognosis of patients. This article reviews the latest research progress of risk factors and intervention measures related to PT after allo-HSCT, in order to provide reference for the prevention and treatment of PT after transplantation.

Clinical Study of Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival.@*METHODS@#A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed.@*RESULTS@#For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005).@*CONCLUSION@#The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.

Comparision of Allogeneic Hematopoietic Stem Cell Transplantation between Children with Thalassemia of Different Ages / 中国实验血液学杂志

OBJECTIVE@#To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation.@*METHODS@#The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups.@*RESULTS@#The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups.@*CONCLUSION@#Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.

Afectación ocular en la enfermedad injerto contra huésped / Ocular damage in graft-versus-host disease

RESUMEN El trasplante alogénico de precursores hematopoyéticos está indicado en el tratamiento de diversos trastornos de la sangre, sobre todo en las neoplasias malignas. La enfermedad injerto contra huésped es la complicación principal de los trasplantes alogénicos de órganos hematopoyéticos. Es una enfermedad inmunológica provocada por la interacción entre el donante y el receptor, mediante respuestas innatas y adaptativas. Con gran frecuencia afecta la piel y el sistema gastrointestinal. Diferentes pueden ser las manifestaciones oculares, pero son las alteraciones de la superficie ocular las más frecuentes. Los cambios en la superficie ocular pueden provocar ceguera. El diagnóstico y el tratamiento precoz mejoran el pronóstico. Además del tratamiento general de la enfermedad es necesario instaurar medidas específicas para controlar las alteraciones oculares. Se realizó una revisión sobre los artículos publicados con el objetivo de conocer sobre la enfermedad injerto contra huésped y su afectación ocular(AU)

ABSTRACT Allogeneic transplantation of hematopoietic precursors is indicated in the treatment of various blood disorders, particularly malignant neoplasms. Graft-versus-host disease is the main complication of allogeneic transplants of hematopoietic organs. GVHD is an immunological condition caused by the interaction between the donor and the recipient manifested as innate and adaptive responses. It very often affects the skin and the gastrointestinal system. A variety of ocular manifestations may also occur, the most common of which are ocular surface alterations. Changes in the ocular surface may cause blindness. Early diagnosis and treatment improve prognosis. Besides the general treatment of the disease it is necessary to implement specific measures to control ocular alterations. A review was conducted of published papers on the topic to become acquainted with graft-versus-host disease and the ocular damage it causes(AU)

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)

Características Clínicas e Complicações do Transplante Haploidêntico com Ciclofosfamida Pós-Transplante: Implicações para a Enfermagem / Clinical Characteristics and Complications of the Haploidentical Transplantation with Post-Transplant Cyclophosphamide: Implications for Nursing / Características Clínicas y Complicaciones del Trasplante Haploidéntico con Ciclofosfamida Post-Trasplante: Implicaciones para la Enfermería

Introdução: O transplante haploidêntico (haplo) vem crescendo em números e se tornando uma alternativa viável para pacientes sem doadores compatíveis. Uma assistência de enfermagem qualificada também é muito importante para o seu sucesso. Portanto, torna-se necessário adquirir conhecimentos e habilidades no assunto. Objetivo: Descrever as características clínicas e complicações do haplo com ciclofosfamida pós-transplante e discutir suas implicações para a assistência de enfermagem. Método: Revisão integrativa da literatura publicada a partir de 2014, pesquisada nas bases da Biblioteca Virtual em Saúde com o descritor "haploidentical transplantation" e selecionada com critérios pré-definidos. Resultados: Vinte e cinco textos foram revisados; todos da área médica e compostos principalmente de estudos de coorte retrospectivos com amostras pequenas. Entre as características mais prevalentes, destacaram-se: a mãe como principal doadora para crianças (5/7 estudos); regime não mieloablativo (52%); e enxerto de sangue periférico (56%). Além da doença enxerto versus hospedeiro e da rejeição, as complicações mais descritas foram: cistite hemorrágica por vírus BK (56%) e reativação do citomegalovírus (48%); e as com maiores variações nas frequências foram mucosite (8% a 100%) e febre não infecciosa (22% a 100%). As principais causas de mortalidade foram a recaída da doença (3% a 35%) e as infecções (3% a 32%). Conclusão: Esta revisão alertou para a necessidade de aprimoramento da assistência na administração da ciclofosfamida pós-transplante, no suporte aos doadores e no manejo da febre não infecciosa, das infecções virais e da cistite hemorrágica, para que haja melhora na qualidade de vida dos pacientes e diminuição na morbidade e na mortalidade relacionadas ao haplo.

Introduction: Haploidentical Transplantation (haplo) has been growing in numbers and becoming a viable alternative for patients without compatible donors. Qualified nursing care is also very important for its success. Therefore, it becomes necessary to acquire knowledge and skills about the subject. Objective: To describe clinical characteristics and complications of haplo with post-transplant cyclophosphamide and discuss its implications for nursing care. Method: Integrative literature review published from 2014, searched in the bases of the "Biblioteca Virtual em Saúde" with the descriptor "haploidentical transplantation" and selected with predefined criteria. Results:Twenty-five texts were reviewed, all of them of the medical area and consisting mainly of retrospective cohort studies with small samples. Among the most prevalent characteristics, the following were outstanding: the mother as the main donor for children (5/7 studies); non-myeloablative regimen (52%) and peripheral blood graft (56%). In addition to graft versus host disease and rejection, the most described complications were: BK virus hemorrhagic cystitis (56%) and reactivation of cytomegalovirus (48%); and the ones with the highest variations in frequencies were mucositis (8% to 100%) and non-infectious fever (22% to 100%). The main causes of mortality were relapse of the disease (3% to 35%) and infections (3% to 32%). Conclusion: This review warned about the necessity of improving the care in the administration of post-cyclophosphamide, the support to donors and management of non-infectious fever, viral infections and hemorrhagic cystitis to improve the quality of life of patients and reduce haplo-related morbidity and mortality.

Introducción: El diagnóstico precoz del riesgo nutricional puede mejorar el pronóstico de los pacientes onco-hematológicos. Objetivo: Describir el estado nutricional en los pacientes onco-hematológicos y evaluar los factores asociados al riesgo nutricional en los pacientes onco-hematológicos de un Hospital Universitario Terciario de Fortaleza - Ceará. Método: Estudio transversal que incluyó a 127 pacientes adultos internados. Los datos de diagnóstico clínico y demográfico fueron recolectados a través de análisis de prontuarios. El estado nutricional fue evaluado por el índice de masa corporal (IMC), circunferencia braquial (CB) y por la aplicación de la herramienta de clasificación de riesgo nutricional - NRS-2002. Resultados: Diferentes parámetros, hubo divergencias en el estado nutricional. La mayoría de la muestra presentaba riesgo nutricional de acuerdo con la evaluación de la NRS-2002 70,1% (n=89), seguida por la CB 33,9% (n=43) y por IMC 8,7% (n=11). Se observó una correlación positiva significativa entre el IMC y la edad [r=0,313, p<0,001] y CB [r=0,846, p<0,001]. Se observó una asociación significativa NRS-2002≥3, e IMC<18,5 kg/m² (p=0,023) y CB desnutrida (p=0,001). Hubo asociación significativa entre IMC<18,5kg/m² y CB desnutrida (p=0,001), y entre residir en zona urbana y presentar CB adecuado (p=0,023). Conclusión: Alta prevalencia de riesgo nutricional, así como una asociación significativa entre riesgo nutricional y bajos valores de IMC y CB, y residir en zonas rurales. Hay la necesidad de utilizar una combinación de indicadores para diagnosticar de forma más precisa y precoz el estado nutricional de estos pacientes.

Doença do Enxerto-versus-hospedeiro ocular: Revisão / Graft-versus-Host Disease: Review

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.

Enfermedad injerto contra huésped cutánea crónica tipo vitiligo. Caso clínico / Vitiligo type cutaneous manifestation of chronic graft-versus-host disease. Case report

Resumen: Introducción: La enfermedad injerto contra huésped (EICH) se produce por una respuesta patoló gica y destructiva del organismo, como resultado de la interacción entre linfocitos T inmunocompetentes del donante y los antígenos del tejido receptor. Se considera la complicación más grave del trasplante de células madres hematopoyéticas, descrito con mayor frecuencia posterior al trasplante de médula ósea (TMO). La piel suele ser el primer órgano y el más comúnmente afectado, tanto en su forma aguda como crónica, con un espectro clínico de presentación variable. Objetivo: Reportar un caso de vitiligo como manifestación de EICH cutánea crónica, signo de baja prevalencia, cuyo reconocimiento podría ayudar a la sospecha de esta grave complicación. Caso clínico: Escolar de sexo masculino de 8 años de edad, con antecedente de leucemia linfoblástica aguda (LLA) diagnosticada a los 3 años de edad, con recaída combinada medular y del sistema nervioso central (SNC) con enfer medad mínima positiva en los 3 años siguientes. Cuatro años posterior al diagnóstico de LLA, recibió TMO alogénico y siete meses después presentó múltiples nevos melanocíticos con hipopigmentación perilesional y máculas acrómicas en cara, tronco y extremidades, asintomáticas. La biopsia de piel fue compatible con EICH crónica tipo vitiligo y esclerodermiforme. Recibió tratamiento tópico con Tacrolimus, logrando estabilización del cuadro. Conclusiones: La EICH conlleva a la aparición de autoanticuerpos que podrían actuar como un factor desencadenante en la aparición de enfermedades autoinmunes, como lo es el vitiligo. En consecuencia podría explicar esta manifestación, poco descri ta en la literatura, de la EICH cutánea crónica.

Abstract: Introduction: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation. Objective: To report a case of vitiligo as a manifestation of cutaneous chronic GVHD, a low prevalence sign, which recognition could help to suspect this severe compli cation. Case report: 8 years old male, diagnosed with acute lymphoblastic leukemia (ALL) at 3 years old, had a combined medullary and central nervous system (NCS) relapse with minimal positive disease 3 years afterwards. After 4 years ALL was diagnosed, he received an allogeneic bone marrow transplant. Seven months after the BMT he presented multiple melanocytic nevi with peripheral hypopigmentation, and some isolated asymptomatic, confluent achromic macules on the face, trunk and limbs. The skin biopsy was compatible with chronic vitiligo and sclerodermiform type GVHD. He received topical treatment with Tacrolimus, achieving clinical stabilization. Conclusions: GVHD leads to the appearance of autoantibodies that could act as a trigger in the onset of autoimmune diseases, such as vitiligo. Consequently it could explain this poorly described manifestation in the literature of chronic cutaneous GVHD.

Enfermedad injerto contra huesped: sus manifestaciones bucales / Graft-versus-host disease: its oral manifestations

La enfermedad injerto contra huésped es la principal complicación que sufren los pacientes que han recibido trasplante alogénico. Se produce como consecuencia de una reacción inflamatoria exagerada mediada por los linfocitos del donante y estimulada por aquellos tejidos que han sido lesionados por la enfermedad de base, por las infecciones previas o por el tratamiento de acondicionamiento. El diagnóstico es clínico e histopatológico. Los pacientes presentan rash maculopapular pruriginoso y doloroso que puede extenderse por toda la superficie corporal, fiebre, vómito, náuseas, diarrea y anorexia. En la mucosa bucal se observan erosiones ulceradas, extremamente dolorosas y pueden ser la primera o la única manifestación detectable clínicamente de esta enfermedad. El objetivo es presentar un caso de enfermedad de injerto contra huésped. Se trata de una mujer de 54 años de edad con linfoma no-Hodgking, que recibió tratamiento con quimioterapia, radioterapia y trasplante de células madre hematopoyéticas en el 2009. Tres meses después, presentó lesiones en la piel diagnosticadas como enfermedad injerto contra huésped y tratadas con corticoesteroides, a los seis meses fue remitida al odontólogo porque se quejaba de ardor en la boca, xerostomía y dificultad para masticar, tenía úlceras en la mucosa bucal y en la lengua. En la ocasión recibió tratamiento con corticoesteroides, clorhexidina, orientaciones de higiene bucal y controles clínicos permanentes. Aunque existen protocolos para la prevención y el tratamiento de la enfermedad injerto contra el huésped, su frecuencia ha aumentado en los últimos años debido al incremento en el número de trasplantes. Por esta razón, es fundamental que el odontólogo forme parte del grupo multidisciplinario que asiste al paciente y que esté familiarizado con los signos y síntomas de esta enfermedad en la mucosa bucal, pues las manifestaciones clínicas pueden ser las únicas para realizar el diagnóstico(AU)

Graft-versus-host disease is the main complication following an allogeneic tissue transplant. It is caused by an exaggerated inflammatory reaction mediated by donor lymphocytes and stimulated by tissues lesioned by the underlying disease, by previous infection or by the conditioning treatment. The diagnosis is clinical and histopathological. Patients have itchy and painful maculopapular rash that can spread throughout the entire body surface, fever, vomiting, nausea, diarrhea and anorexia. Extremely painful ulcerated erosions occur in the oral mucosa, which may be the first or the only clinically detectable manifestation of the disease. The objective is to report a case of graft-versus-host disease. A 54 year-old woman with non-Hodgkin lymphoma was treated with chemotherapy, radiation therapy and hematopoietic cell transplantation in 2009. After three months, she presented skin lesions diagnosed as graft-versus-host disease and received corticosteroids. Six months later, she was referred to the dentist because of complaints of xerostomia, a burning sensation in her mouth and difficulty chewing. She also had ulcers in the oral mucosa and tongue. This time she received topical corticosteroid therapy, chlorhexidine, oral hygiene instructions and permanent clinical control. Despite some protocols for the prevention and treatment of graft-versus-host disease, its frequency has recently risen due to the increasing number of transplants. For this reason, it is essential for the dentist to be part of the multidisciplinary team treating the patient, and familiar with the signs and symptoms of the disease, since clinical manifestations may be the only ones at hand to make the diagnosis(AU)

Clinical and histological study of permanent alopecia after bone marrow transplantation

Abstract: BACKGROUND: Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. OBJECTIVE: the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. METHODS: data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. RESULTS: Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. CONCLUSION: The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods.

cGVHD-Related Caries and Its Shared Features with Other 'Dry-Mouth'-Related Caries

Several systemic diseases and their medical treatment may predispose the development of aggressive dental caries. Head and neck radiotherapy, chemotherapy, Sjögren's syndrome and long-standing treatment with drugs that induce hyposalivation are some of these conditions. The aim of this article is to describe the clinical features of five patients who developed chronic graft-versus-host-disease (cGVHD) as a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and, in spite of close dental follow-up, subsequently developed rampant caries. In these cases, the restorations showed early failure and the caries still progressed until generalized teeth destruction. The majority of the teeth therefore had to be extracted due to advanced dental caries and rapid clinical progression. Herein the term "cGVHD-related caries" is proposed to describe this under-recognized complication of cancer treatment that may evolve in allo-HSCT recipients that develop cGVHD. This condition is poorly recognized in the literature and may represent the final result of the clustering of oral complications in cGVHD patients, including mucositis, oral pain, hyposalivation, taste loss and oral infections, leading to rampant caries due to impaired oral hygiene and increased intake of highly cariogenic food. Consequently, the knowledge of this oral complication should improve the medical and dental management of cGVHD oral manifestations and improve the quality of life of patients with this post allo-HSCT complication.

Diversas doenças sistêmicas e seus tratamentos podem predispor ao desenvolvimento de cáries dentárias agressivas. A radioterapia de cabeça e pescoço, quimioterapia, síndrome de Sjögren e tratamentos prolongados com as drogas que induzem a hipossalivação são algumas destas condições. O objetivo deste artigo é descrever as características clínicas de cinco pacientes que desenvolveram doença do enxerto contra hospedeiro crônica (DECHc) como uma complicação do transplante alogênico de células-tronco hematopoiéticas (aloTCTH) e, apesar do acompanhamento periódico com dentistas, desenvolveram cáries rampantes. Nestes casos relatados, as restaurações mostraram falhas precoces e as cáries continuaram progredindo até a destruição generalizada dos dentes. A maioria dos dentes, portanto, foi extraída devido à cárie avançada e rápida progressão clínica. Neste artigo, o termo "cáries relacionadas à DECHc" é proposto para descrever esta complicação pouco conhecida do tratamento do câncer, que se manifesta em receptores de TCTH que desenvolvem DECHc. Esta condição é pouco reconhecida na literatura e pode representar o resultado final do agrupamento das complicações bucais em pacientes com DECHc, incluindo mucosite, dor oral, hipossalivação, perda de paladar e infecções orais, levando à cárie rampante devido à dificuldade de higiene oral e aumento da ingestão de alimentos altamente cariogênicos. Por consequência, o conhecimento desta complicação oral deve melhorar os tratamentos médico e odontológico das manifestações bucais da DECHc e melhorar a qualidade de vida dos pacientes com esta complicação após o TCTH.

Histopathologic diagnosis of chronic graft-versus-host disease of the oral mucosa according to the National Institutes of Health Consensus / Diagnóstico histopatológico da doença do enxerto contra hospedeiro crônica da mucosa oral conforme Consenso do National Institutes of Health

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 ...

Enfermedad de injerto contra huésped en trasplante de órgano sólido / Graft versus host disease in solid organ transplantation

La enfermedad de injerto contra huésped es una complicación infrecuente en pacientes trasplantados de órgano sólido. Se trata de un proceso causado por linfocitos T del donante transferidos en el injerto. En el 75% de los casos el compromiso cutáneo es la primeramanifestación y de forma característica nunca compromete el injerto. Progresa de manera rápida con afectación sistémica hasta la muerte en la mayoría de los casos. El diagnóstico se basa en la suma de hallazgos clínicos e histopatológicos y en la detección de quimerismo linfocitario para instaurar el tratamiento de forma precoz...

DECH crônica: fator preditivo para rinossinusite no transplante de medula óssea / Chronic GVHD: predictive factor for rhinosinusitis in bone marrow transplantation

INTRODUÇÃO: transplante de medula óssea (TMO) é uma opção de tratamento para doenças hematológicas, tumorais e imunodeficiências e tem sido realizado com maior freqüência. O TMO predispõe a infecções de VAS e complicações, dentre estas as rinossinusites (RS). Quimioterapia, radioterapia, infecções virais, antibioticoterapia e doença do enxerto versus hospedeiro (DECH) são fatores predisponentes para RS. OBJETIVO: Verificar freqüência das RS no TMO e relação com DECH. Tentar estabelecer qual melhor tratamento para as RS no TMO. MÉTODO: Avaliação otorrinolaringológica de 2 grupos com 35 (gI) e 24 (gII) pacientes, antes e depois do TMO; e tratados individualmente com antibióticos e/ou punção de seios maxilares e/ou sinusectomia endoscópica. RESULTADOS: Nenhum apresentou RS antes do TMO; 42,8 por cento dos TMO do gI tiveram RS e 34 por cento, DECH; enquanto 58 por cento do gII tiveram RS e 25 por cento, DECH. No total, 49 por cento tiveram RS e 30,5 por cento com DECH. Houve significativa maior freqüência de RS em DECH crônica. A cirurgia foi indicada para tratamento de RS no TMO com DECH crônica. CONCLUSÃO: A freqüência de RS no TMO foi de 49 por cento; DECH crônica é um fator predisponente para RS; a sinusectomia pode ser necessária nos pacientes com DECHc e RS.

INTRODUCTION: Bone marrow transplantation (BMT) is a treatment option for hematological diseases and immunodeficiency. It is frequently used today. BMT predisposes patients to upper airway infections and its complications, such as rhinosinusitis (RS). Chemotherapy, radiotherapy, viral infections, antibiotic therapy, graft versus host disease (GVHD) are rhinosinusitis predisposing conditions. AIM: to investigate RS frequence in this population and its relationship to GVHD; to try and establish the best treatment for RS in these patients. METHOD: ENT evaluation of two groups. One group with 35 patients (gI) and another with 24 patients (gII), before and after BMT. They were treated with antibiotics, maxillary sinus punction or endoscopic sinusectomy. RESULTS: none of them had RS before BMT. 42.8 percent from gI had RS and 34 percent had GVHD; in the gII, 58 percent had RS and 25 percent had GVHD. 49 percent from both groups had RS and 30.5 percent had GVHD. There was significantly more RS in chronic GVHD patients. Surgery was used to treat RS in chronic GVHD patients who underwent BMT. CONCLUSION: RS frequence was 49 percent; GVHD is a predisposing condition to RS; sinusectomy may be necessary to control RS in GVHD patients.

Enfermedad de injerto versus huésped / Graft-versus-host disease

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.

Squamous cell carcinoma of the tongue after bone marrow transplantation in a patient with Fanconi anemia

A anemia de Fanconi (AF) é uma doença autossômica recessiva heterogênea que pode causar uma variedade de alterações congênitas e de desenvolvimento. As características mais importantes da AF são a falência progressiva de medula óssea e o desenvolvimento de condições malignas, como leucemia mielóide aguda e tumores sólidos. Este artigo relata o caso de um paciente de 12 anos com AF atendido no Serviço de Estomatologia e Prevenção do Câncer Bucomaxilofacial do Hospital São Lucas (Brasil), que havia sido submetido a transplante de medula óssea (TMO) aos 5 anos e apresentaava lesões características da doença do enxerto versus hospedeiro (DEVH) crônica. O paciente foi regularmente acompanhado no Serviço e, 11 anos após a realização do TMO, desenvolveu um carcinoma epidermóide de língua, considerado com sendo uma condição não-tratável. O pactiente faleceu por asfixia poucos meses depois aos 16 anos. As razões para a ocorrência dessa condição maligna ainda são incertas, podendo estar relacionadas com a instabilidade cromossômica característica da AF, com fatores relacionados ao TMO ou com a DEVH. O acompanhamento sistemático desses pacientes permite a realização de abordagens terapêuticas precoces e menos agressivas quando necessário.

Enfermedad injerto versus huesped: manifestación-enterocólica y diagnóstico diferencial / Graft versus host disease: gastrointestinal manifestation and differential diagnosis

La enfermedad de injerto contra huésped es un síndrome que ocurre en pacientes inmuno-deprimidos generalmente post-trasplante de médula ósea, caracterizado en su etapa aguda por manifestaciones dermatológicas, hepáticas y gastrointestinales. El diagnóstico oportuno es fundamental, ya que puede disminuir significativamente la morbimortalidad. Dentro del diagnóstico diferencial de las manifestaciones gastrointestinales se incluye enterocolitis neutropénica y colitis pseudomembranosa. Mediante tomografía computada, hay signos que apuntan a su diagnóstico, como dilatación focal de asas, y refuerzo significativo de la mucosa enterocólica.

Hemorrhagic Cystitis Following Allogeneic Hematopoietic Cell Transplantation

We conducted a retrospective study to investigate the incidence, risk factors, and clinical features of hemorrhagic cystitis (HC) following allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients who developed HC after allo-HCT were identified from the HCT database of the Asan Medical Center and their medical records were reviewed. From December 1993 to August 2001, a total of 210 adult patients underwent allo-HCT. Fifty-one patients developed HC with a cumulative incidence of 25.7%. The median onset of HC was post-transplant day 24 (range, -2 to 474), and the median duration was 31 days (range, 8 to 369). Significant risk factors for HC by univariate analysis included diagnosis of chronic myelogenous leukemia (p=0.028), unrelated HCT (p=0.029), grade III-IV acute graft-versus-host disease (GVHD) (p<0.001), extensive chronic GVHD (p=0.001), and positive cytomegalovirus antigenemia between post transplant days 31 and 60 (p=0.031). Multivariate analysis showed that grade III-IV acute GVHD was the most important risk factor for the occurrence of HC after allo-HCT (odds ratio, 3.38; 95% CI, 1.36-8.39). Late-onset HC, which occurred beyond 3 weeks after allo-HCT, was more frequently associated with GVHD than earlyonset HC (p=0.007). Our data suggest that a portion of late-onset HC might be a manifestation of GVHD.