Extracorporeal photopheresis in chronic graft-versus-host disease: clinical description and economic study

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.

Can NLR be a biomarker for mucositis and gvhd in patients undergoing allogeneic HSCT?

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

Clinical characteristics of hematologic disease patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation and their effects on prognosis / 白血病·淋巴瘤

Objective:To explore the clinical characteristics and influencing factors of hematologic disease patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their effects on the prognosis of patients.Methods:The clinical data of 225 hematologic disease patients who underwent allo-HSCT from January 2014 to February 2021 in the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The efficacy of allo-HSCT, post-transplantation infection, as well as the incidence of cGVHD and its related factors, and its effect on the overall survival (OS) rate, disease-free survival (DFS) rate, cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) rate of patients according to Seattle diagnostic criteria and National Institutes of Health (NIH) diagnostic criteria were analyzed.Results:All 225 hematologic disease patients had hematopoietic reconstruction after allo-HSCT. Among the 225 patients, 156 patients (69.33%) had early infection (207 times), and 92 patients (40.89%) had late infection (107 times). According to the Seattle diagnostic criteria, 58 patients developed cGVHD (111 times), with a cumulative incidence of 39.5%. The involved organs included skin (33 times), liver (32 times), eyes (19 times), lung (11 times), oral cavity (10 times), intestine (4 times) and hematological system (twice). Multivariate Cox regression analysis showed that acute graft-versus-host disease (aGVHD) was an independent influencing factor for cGVHD ( HR= 3.706, 95% CI 2.025-6.783, P<0.001). Compared to patients without cGVHD, patients with cGVHD had lower 5-year CIR (4.0% vs. 21.8%, P= 0.010) and higher 5-year NRM rate (25.5% vs. 11.8%, P= 0.029), while 5-year OS rate (72.5% vs. 73.6%, P= 0.908) and DFS rate (64.6% vs. 65.9%, P= 0.670) between the two groups had no statistical difference. Compared to patients with limited cGVHD, patients with extensive cGVHD had lower 5-year OS rate (56.0% vs. 83.9%, P= 0.035), lower 5-year DFS rate (52.0% vs. 73.4%, P = 0.038) and higher 5-year NRM rate (43.0% vs. 13.0%, P = 0.018). More erythrocyte suspension infusion during the transplantation was an independent influencing factor for early infection ( P = 0.011). Blood type incompatibility between donor and recipient ( P = 0.017), limited cGVHD ( P = 0.039) and extensive cGVHD ( P = 0.003) were independent influencing factors for late infection. According to the NIH diagnostic criteria, 5 patients (8.62%) who developed cGVHD after 100 days of transplantation were reclassified as aGVHD, and 12 patients (20.69%) were reclassified as overlap syndrome. The cumulative incidence of cGVHD was 36.4%, and aGVHD was the only independent influencing factor for cGVHD ( P<0.001). Compared to patients without cGVHD, patients with cGVHD had lower 5-year CIR (6.7% vs.21.7%, P = 0.006) and higher 5-year NRM rate (26.1% vs. 12.0%, P = 0.035), while 5-year OS rate (73.7% vs. 73.2%, P = 0.845) and DFS rate (64.9% vs. 65.7%, P = 0.522) between the two groups had no statistical difference. Conclusions:The incidence of cGVHD after allo-HSCT in hematologic disease patients is high, and there are many organs involved. cGVHD can reduce the relapse rate of patients, but severe cGVHD increases the mortality of patients. aGVHD is the only independent influencing factor for cGVHD.

Clinical features of 24 cases of scleroderma-like cutaneous graft-versus-host disease / 中华皮肤科杂志

Objective:To investigate clinical features of and risk factors for scleroderma-like cutaneous graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation.Methods:Clinical data were collected from 24 patients with scleroderma-like cutaneous GVHD in Department of Dermatology, Peking University People′s Hospital from 2014 to 2019. Clinical features, treatment, prognosis, and possible factors influencing the development of scleroderma-like cutaneous GVHD were analyzed retrospectively.Results:Among the 24 patients, 11 were males, and 13 were females, aged 33 ± 12 years; 20 were human leukocyte antigen (HLA) -identical recipients, 4 were HLA-haploidentical recipients; GVHD occurred 18.5 (8.0, 30.9) months after transplantation. Nineteen patients had discontinued anti-rejection therapy or received low-dose anti-rejection drugs before the onset of GVHD. Fifteen patients presented with generalized scleroderma-like lesions, 1 with linear scleroderma-like lesions, 5 with morphea-like lesions, and 3 with fasciitis-like lesions. None of the 15 patients with generalized scleroderma-like GVHD had Raynaud syndrome. Thirteen patients were accompanied by graft rejection in other systems, 8 had joint mobility limitations, and 1 developed cutaneous squamous cell carcinoma secondary to chronic skin ulcers. All patients were treated with systemic glucocorticoids and immunosuppressive agents, and 11 also with topical glucocorticoids. An intensive follow-up was carried out in 11 patients, of whom 3 achieved marked improvement, 4 achieved improvement, 2 experienced exacerbation, and 2 died. A total of 223 patients with non-sclerodermatous cutaneous GVHD admitting during the same period served as controls, and the proportion of HLA-identical patients was significantly higher in the scleroderma-like cutaneous GVHD group (20/24, 83.3%) than in the non-sclerodermatous cutaneous GVHD group (47/223, 21.1%; P < 0.001) . Conclusions:Scleroderma-like cutaneous GVHD commonly occurs late, and can mimic clinical manifestations of all 4 types of spontaneous scleroderma. HLA-identical transplants, premature discontinuation or excessive dose reduction of anti-rejection drugs may be risk factors for scleroderma-like cutaneous GVHD.

O papel da odontologia no diagnóstico da doença enxerto-contra-hospedeiro / The role of dentistry in the diagnosis of Graft-versus-host disease

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.

Hematoma duodenal posvideoendoscopia digestiva alta para diagnóstico de enfermedad de injerto contra huésped en pediatría: a propósito de dos casos / Duodenal hematoma after upper gastrointestinal endoscopy in pediatric graft vs host disease: Report of two cases

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.

Implicaciones clínicas de las quimiocinas y sus receptores en la medicina transfusional y el trasplante / Clinical implications of chemokines and their receptors in transfusion medicine and transplantation

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)

Treatment of oral chronic graft-versus-host disease: a retrospective cohort study / Tratamento da doença do enxerto contra hospedeiro crônica oral: um estudo de coorte retrospectivo

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.

Manifestaciones cutáneas de la enfermedad injerto versushuésped en una población pediátrica y de adultos jóvenes / Cutaneous manifestations of graft versus host disease in a population of pediatric and young adults patients

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

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.

Rehabilitation in Children With Sclerodermoid Chronic Graft-Versus-Host Disease: Case Series

Joint contracture in chronic graft-versus-host disease (cGVHD) is refractory to treatment, and tends to deteriorate gradually over time. There is scant clinical research focusing on timing and intensity of rehabilitation on joint contractures in children with sclerodermoid cGVHD after hematopoietic stem cell transplantation. We retrospectively reviewed rehabilitative therapeutic effects in 6 children with sclerodermoid cGVHD, whose clinical records documented their condition, before and after rehabilitation therapies. Three children who started treatment within a mean of 2 months after the onset of joint symptoms, and who underwent home-based exercise twice daily for 30 minutes showed more prominent improvement in range of motion compared with the other 3 children, who started rehabilitation therapy later than 6 months after onset of joint symptoms, without regular home-based exercise.

Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old / 中华血液学杂志

Objective@#To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old.@*Methods@#From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed.@*Results@#①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019].@*Conclusion@#The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.

Impact of mycophenolate mofetil prophylaxis duration on acute graft-versus-host disease after haploidentical stem cell transplantation / 中华血液学杂志

Objective@#To investigate the impact of mycophenolate mofetil (MMF) prophylaxis duration on acute graft-versus-host disease (aGVHD) after haploidentical stem cell transplantation (haplo-HSCT) using 'Beijing Protocol’.@*Methods@#Adult patients (≥14 years) received haplo-HSCT in Peking University Institute of Hematology from Sep, 2016 to Mar, 2017 were retrospectively reviewed if they fulfilled the criterias: ①diagnosed with hematological maligancies; ②standard-risk status at haplo-HSCT. A total of 237 patients [including 102 patients with long MMF duration (defined as started on day -9 with 100 mg/d, adjusted to 500 mg/d from day +30 and discontinued on day +45 to +60 or occurrence of CMV/EBV reactivation or late-onset hemorrhagic cytitis), and 135 patients with short MMF duration (defined as started on day -9 with 500 mg/d and discontinued on the day achieved neutrophil engraftment)] were reviewed. The incidence of aGVHD, virus infection and overall survival (OS) were compared between the two groups.@*Results@#The median durations of MMF prophylaxis of long and short duration groups were 27(7-71) and 15(9-24) days, respectively after haplo-HSCT. There were no differences of baseline characteristics (including sex, patient age, disease, mismatched HLA loci, donor-recipient relation, donor-recipient sex and donor age) between the two groups. The incidences of the grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in long and short duration groups were 31.1% versus 17.6% (P=0.018) and 7.4% verus 7.8% (P=0.900), respectively. The duration of MMF prophylaxis was not found to be associated with gradeⅡ-Ⅳ aGVHD by the multivariate analysis. There were no significant differences in terms of CMV viremia, EBV viremia, hemorrhagic cytitis and OS between the two groups.@*Conclusion@#Prophylaxis with short duration MMF in the setting of 'Beijing protocol’ haplo-SCT was not associated with increased acute GVHD with no impact on OS, which indicated that short duration MMF might be a feasible GVHD prophylaxis regimen.

Clinical analysis of six cases with the de novo glomerulitis after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated.@*Results@#The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived.@*Conclusion@#The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.

Research progress of topical treatment of oral chronic graft versus host disease: a review / 中华口腔医学杂志

Oral cavity is one of the main organs involved in chronic graft versus host disease (cGVHD). Oral cGVHD seriously affects the patient's quality of life. Topical use of glucocorticoid and other agents is the primary topical treatment of oral cGVHD, oral photochemical therapy and various new methods have also been applied in patients recently. These important adjuvant therapies are based on the systemic use of drugs such as immunosuppressive agents, and sometimes, may be the only effective treatment for oral cGVHD. This review will focus on the application of topical agent treatment and oral photochemotherapy in oral cGVHD patients.

Treatment of four cases of Fanconi anemia by allogeneic hematopoietic stem cell transplantation with low intensity conditional regimen / 中华血液学杂志

Objective@#To evaluate the efficiency and safety of low intensity conditional regimen for children with Fanconi anemia (FA) receiving allogenic hematopoietic stem cells transplantation (allo-HSCT).@*Methods@#Four patients diagnosed as Fanconi anemia were enrolled in this study. One patient received HLA-identical sibling donor hematopoietic stem cell transplantation, two patients underwent unrelated donor matched (UD) HSCT, and one patient received unrelated cord blood transplantation. The conditional regimen consisted of Busulfan with low dose of cyclophosphamide.@*Results@#All 4 cases succeeded in allo-HSCT. The median time for neutrophils engraftment was 11(9-15) day, median time to platelets (PLT) engraftment was 12 (8-28) day. One case occurred with grade I of aGVHD, 1 case with hemorrhagic cystitis. No patient happened with hepatic veno-occlusive disease (VOD).@*Conclusion@#Low intensity of conditional regimen is efficient and safe which should be recommended for FA patients with HSCT.

Anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To investigate the efficacy of anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Methods A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 2016 were enrolled in this study.Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8).Anti-CD25 monoclonal antibodys (mAb) were administrated on days 1,4,8,15,and 22.The efficacy of anti-CD25 mAb was evaluated at day 28 after the initial treatment.The associated factors of clinical outcome were analyzed.Results The overall response (OR) rate of anti-CD25 mAb was 75％ (60/80),with complete response (CR) rate,partial response (PR) rate and no response(NR) rate 52.5％ (42/80),22.5％ (18/80),and 25％ (20/80),respectively.GVHD-relapse was not observed with a median follow-up time of 394.5 days (range,12-1 761 days).The 6-month overall survival (OS) rate was 68.4％ (95％CI 63.2％-73.6％).The 1-year OS rate was 63.1％ (95％CI 57.6％-68.6％),and 2-years OS rate was 50.7％ (95％CI 44.3％-57.1％).Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6％ (95％CI 27.2％-38％) and 41.7％ (95％CI 35.3％-48.1％),respectively.The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9％ (95％CI 26.4％-39.4％) and 38.9％ (95％CI 31.8％-46.0％).By univariate and multivariate analysis,liver involvcment was an independent poor risk factor of SR-aGVHD (OR=4.66,95％ CI 1.145-18.962,P=0.032).Conclusion Anti-CD25 mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present.Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

Experience in diagnosis and treatment of acute graft-versus-host disease after liver transplantation of 8 cases / 临床肝胆病杂志

ObjectiveTo investigate the diagnosis and treatment of acute graft-versus-host disease (aGVHD) after liver transplantation. MethodsThis report included 8 patients treated with liver transplantation who were admitted to the Liver Transplantation Center of Beijing YouAn Hospital from April 2011 to August 2016. The key points in the diagnosis of aGVHD and the experience in the treatment of this disease were summarized. ResultsThe key points in the diagnosis of aGVHD after liver transplantation were as follows: (1) aGVHD usually occur at two weeks to two months after liver transplantation; (2) fever, rash, diarrhea, and reduced whole blood cell count are typical clinical symptoms; (3) the percentage of donor T lymphocytes in peripheral blood is more than 10%; (4) there are typical histopathological manifestations. The experience in the treatment of aGVHD after liver transplantation were as follows: the overall steroid response rate is 20%-50%, and methylprednisolone (1.5 mg·kg-1·d-1, one week) is recommended; high-dose glucocorticoids are not recommended, thus avoiding increased infection risk; high-dose immunosuppressant is one of the causes of aGVHD, and excessive application of immunosuppressant should be avoided in clinical practice; the prevention of respiratory infection and digestive tract infection was very important; enteral nutrition should be considered; second-line therapies such as siplizumab, antithymocyte globulin, and tumor necrosis factor-alpha inhibitor may play a certain therapeutic role; blood purification can be used to effectively eliminate cytokines and inflammatory mediators, which is helpful to the treatment of aGVHD. ConclusionThe diagnostic criteria for aGVHD after liver transplantation are mainly based on time of onset, clinical symptoms, peripheral blood T lymphocyte chimerism rate, and histopathology. Hormone shock and reducing the dose of immunosuppressant may be effective treatments.

Fototerapia UVB banda estrecha en el tratamiento de la enfermedad injerto contra huésped crónica cutánea: reporte de caso / Narrowband UVB phototherapy for the treatment of cutaneous chronic graft versus host disease: case report

Resumen La enfermedad injerto contra huésped crónica (EICHc) es una complicación frecuente en los pacientes que reciben trasplante de progenitores hematopoyéticos (TPH) alogénico, siendo la piel el órgano más frecuentemente afectado. La EICHc cutánea se presenta con lesiones esclerodermiformes y no esclerodermiformes y frecuentemente requiere tratamiento con inmunosupresores sistémicos, fotoféresis extracorpórea o fototerapia. Los inmunosupresores tienen el potencial de producir importantes efectos adversos, por lo que terapias con mejor perfil de seguridad son claramente necesarias. Presentamos el caso de una paciente de 11 años a quien se le realizó un TPH haploidéntico como tratamiento de una leucemia linfocítica aguda. En su evolución desarrolló EICHc cutánea esclerodermiforme. La paciente recibió tratamiento con luz ultravioleta B de banda estrecha (UVBbe), respondiendo satisfactoriamente en los 2 primeros meses. Existen múltiples reportes y series de casos exitosos sobre el tratamiento con fototerapia en distintas modalidades. En relación a la fototerapia con UVBbe, la literatura es escasa, sin embargo, muestran importantes resultados tanto en las formas esclerodermiformes y no esclerodermiformes de la EICHc cutánea y un buen perfil de seguridad. De todas formas, se requieren estudios prospectivos controlados a gran escala para determinar su efectividad como terapia adjuvante o incluso de primera línea y para definir los esquemas terapéuticos y dosis más efectivas.

Summary Chronic graft-vs-host disease (GVHD) is a frequent complication in patients who receive allogeneic hematopoietic cell transplants (HCTs), and the skin is the most common site of involvement. Chronic cutaneous GVHD can present with sclerotic or nonsclerotic changes and often requires treatment with systemic immunosuppressants, extracorporeal photopheresis, or phototherapy. Immunosuppressants carry the potential of causing important side effects, so additional modes of therapy with better security profiles are clearly needed. We report a case of an eleven year old girl, who received allogeneic HCTs to treat acute lymphocytic leukemia. She developed sclerotic chronic GVHD. The patient underwent treatment with narrowband UV-B phototherapy, and a significant improvement was seen over the first 2 months. There are a number of successful series and case reports on different forms of phototherapy. In relation to narrowband UV-B phototherapy, literature is scarce, although shows important results in sclerotic and nonsclerotic forms of chronic cutaneous GVHD and a good safety profile have been seen. Anyway, large-scale controlled prospective trials are needed to evaluate the effectiveness of phototherapy as adjuvant o even first-line therapy, and to establish the most effective therapy schemes and doses.

Construction of a murine model of chronic graft-versus-host disease by haplo-identical spleen cell infusion / 中华器官移植杂志

Objective For providing experimental platform of chronic graft-versus-host disease (cGVHD),to establish a mouse model by haplo-identical spleen cell infusion.Methods The donor male mice (Balb/cH-2d) and the recipient (Balb/c C57BL/6) F1 H2-d/b (CB6F1) female mice were randomly divided into four groups:3 experimental groups injected with 3 107,6 107 and 9 107 spleen cells,respectively,while the control group received RPMI 1640 solution.H-2d and H-2b were checked to analyze the chimerism in bone marrow cells.Body mass,figure,cutaneous manifestation and survival of recipient mice were observed and scored every 3 days.Pathologic changes of target organs were observed and scored.Results Injection of 6 107 and 6 107 splenocytes in the recipient mice resulted in a chronic disease with a low level of parental cell engraftment steadily.As compared with 3 107 group,the incidence of cGVHD in 6 107 and 9 107 groups were significantly increased (P ＜0.01).But there was no significant difference between 6 107 and 9 107 groups (P＞0.05).Conclusion A murine model of cGVHD after haplo-identical spleen cell infusion of donor is successfully established by injection of 6 107 and 9 107 spleen cells.