Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23.448
Filtrar
1.
N Engl J Med ; 384(1): 11-19, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33406328

RESUMO

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known. METHODS: We conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation. RESULTS: A total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation. CONCLUSIONS: In this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).


Assuntos
Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Adulto , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Sirolimo/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversos , Análise de Sobrevida , Tacrolimo/uso terapêutico , Transplante Homólogo , Adulto Jovem
3.
Nat Commun ; 12(1): 65, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397897

RESUMO

Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Doença Enxerto-Hospedeiro/virologia , Micobioma , Adolescente , Biodiversidade , Humanos , Masculino , Microbiota
4.
Support Care Cancer ; 29(1): 79-84, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803727

RESUMO

BACKGROUND: Verruciform xanthoma (VX) is an uncommon benign epithelial lesion which mainly appears in inflamed oral epithelium. In this study, our aim was to present new cases of oral VX (OVX) in chronic graft-versus-host disease (cGVHD) and review the literature. METHODS: We conducted a retrospective chart review of cGVHD patients (2012-2019) to reveal cases of OVX. The demographics, medical background, clinical presentation, treatment provided, and follow-up were obtained. Additionally, Medline was searched using the terms "graft-versus-host disease," "verruciform xanthoma," and "oral." Of the articles, the above-mentioned demographic and clinical features were retrieved. RESULTS: The patient pool included 133 oral cGVHD patients. Three cGVHD patients (males, aged 15-49 years, post-hematologic malignancy) were diagnosed with OVX. All patients had oral mucosal lichenoid lesions, but not in close proximity to the VX lesion. Medline searches revealed 9 cases of OVX in cGVHD patients reported in the literature. Eleven of the 12 patients had oral mucosal lichenoid lesions. Four patients had multiple OVX lesions. All lesions were asymptomatic. Six patients had lesions in the masticatory mucosa (hard palate and gingiva) and 4 patients had lesions in the buccal mucosa. CONCLUSIONS: To the best of our knowledge, this is the largest published OVX in cGVHD series, including 12 patients. It appears that despite the higher prevalence in cGVHD patients relative to the general population, OVXs do not necessarily develop in sites with lichenoid lesions. It is advised that clinicians be familiar with the clinical and histological features in order to consider OVX in the differential diagnosis of oral lesions in cGVHD patients.


Assuntos
Doença Enxerto-Hospedeiro/patologia , Doenças da Boca/patologia , Mucosa Bucal/patologia , Úlceras Orais/patologia , Xantomatose/patologia , Adolescente , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/diagnóstico , Estudos Retrospectivos , Adulto Jovem
5.
Ter Arkh ; 92(7): 23-30, 2020 Sep 01.
Artigo em Russo | MEDLINE | ID: mdl-33346442

RESUMO

AIM: Analysis of the effectiveness of the MSCs aministration as the second- or third-line therapy of acute GVHD (aGVHD) resistant to glucocorticosteroid treatment. MATERIALS AND METHODS: The study included 35 patients who received MSCs obtained from the bone marrow of healthy donors as a treatment of steroid-resistant aGVHD. The clinical parameters of patients, MSCs cultural characteristics, the MSC expression profile for various genes including those involved in immunomodulation, expression of cells surface markers, the source of MSCs, as well as the frequency and number of MSC administrations were analyzed. RESULTS: Response to therapy was achieved in 74% of cases, a complete response was reached in 13 (37%) patients, partial response/clinical improvement was demonstrated in 13 (37%). This treatment was ineffective in 9 patients. The prediction of a group of patients with good response to MSC therapy turned to be impossible. The differences between the effective and ineffective for the GVHD treatment MSCs samples were found. The effective ones were characterized with a decreased total MSCs production and an increase in the main histocompatibility complex and PDL-1 antigens expression. CONCLUSION: These data allow to select optimal samples for aGVHD treatment that can improve clinical results. aGVHD treatment with MSCs has shown efficacy comparable to other treatment approaches. Given the low percentage of complications and the absence of significant adverse effects, MSC therapy seems to be one of the optimal approaches to the treatment of resistant forms of GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença Aguda , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Transplante Homólogo
6.
Ter Arkh ; 92(7): 43-54, 2020 Sep 01.
Artigo em Russo | MEDLINE | ID: mdl-33346444

RESUMO

AIM: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD). MATERIALS AND METHODS: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR. RESULTS: After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group. CONCLUSION: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Transplante de Microbiota Fecal , Fezes , Doença Enxerto-Hospedeiro/terapia , Humanos , Estudos Prospectivos , Resultado do Tratamento
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1683-1688, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067974

RESUMO

OBJECTIVE: To compare the clinical efficacy between frontline haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) and salvage haplo-HSCT for patients with severe aplastic anemia (SAA). METHODS: A total of 39 patients with severe aplastic anemia or very severe aplastic anemia from May 1st, 2013 to December 31st, 2018 were analyzed retrospectively. All of them underwent bone marrow + peripheral blood hemopoietic stem cell transplantation. There were 20 cases who accepted frontline haplo-HSCT for a median course of 1 (1-3) month, and 19 cases who accepted salvage haplo-HSCT for a median course of 72 (6-168) months. Conditioning regimen: 22 cases received Flu/Cy+ATG, and 17 cases received Bu/Cy+ATG. RESULTS: The time of hematopoietic reconstitution, infection rate, and grade I-Ⅱ and Ⅲ-Ⅳ acute/chronic graft versus host disease showed no statistically significance between the frontline haplo-HSCT group and the salvage haplo-HSCT group. In the frontline haplo-HSCT group, 1 case (5%) failed in second engraftment, in the salvage haplo-HSCT group 2 cases (10.5%) failed in primary engraftment and 4 cases (21.1%) in second engraftment. The incidence of engraftment failure was higher in the salvage haplo-HSCT group than that in the frontline haplo-HSCT group (P=0.04). The median time of follow-up after allo-HSCT was 45 months (ranging from 3 to 92). The mortality was 10% (2/20) in the frontline haplo-HSCT group, and 42.1% (8/19) in the salvage haplo-HSCT group. The estimated 5-year failure-free survival rate (FFS) of the frontline haplo-HSCT group was higher than that of the salvage haplo-HSCT group (90% vs 57.4%) (P=0.02). CONCLUSION: The frontline haplo-HSCT is an effective and safe approach for the patients with severe aplastic anemia who lack a HLA-matched sibling donor.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Humanos , Estudos Retrospectivos , Condicionamento Pré-Transplante
8.
Anticancer Res ; 40(11): 6531-6537, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109594

RESUMO

BACKGROUND: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. PATIENTS AND METHODS: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. RESULTS: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. CONCLUSION: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.


Assuntos
Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Estomatite/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Intervalo Livre de Progressão , Estomatite/complicações , Estomatite/patologia , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
9.
Adv Clin Exp Med ; 29(10): 1221-1230, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33064381

RESUMO

The increasing number of hematopoietic stem cell transplantation (HSCT) procedures and lower transplant-related mortality has led to a growing population of survivors facing long-term increased risk of secondary malignancy, including cutaneous neoplasms. In this review, we aim to discuss the incidence, risk factors and preventive strategies for secondary skin neoplasms after autologous and allogeneic HSCT. Cutaneous neoplasms, such as basal cell carcinoma, squamous cell carcinoma and melanoma, are among the most common solid cancers arising in patients after HSCT. Besides risk factors established in the general population, primary disease, chronic graft-versus-host disease (CGvHD), prolonged immunosuppression, especially with the use of cyclosporine and azathioprine, radiation exposure, light skin color, male sex, and young age at transplantation play a role in the development of cutaneous neoplasms in HSCT recipients. Skin cancer development after HSCT may be explained by cumulative effects of chemotherapy and radiotherapy-induced DNA damage, prolonged immunosuppressive conditions and chronic mucosal inflammation, particularly after allogeneic HSCT. Delayed immune recovery and persistent immunodeficiency in patients with graft-versus-host disease (GvHD) may also contribute to carcinogenesis. Regular dermatological surveillance and prompt recognition of precancerous and cancerous lesions is crucial for patient's prognosis and management.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias Cutâneas , Ciclosporina , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Transplante Homólogo
10.
J Am Dent Assoc ; 151(11): 846-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33121606

RESUMO

BACKGROUND: Long-term survivors of allogeneic hematopoietic cell transplantation will increasingly seek care from dental providers. METHODS: The authors highlight the importance of minimizing oral symptoms and complications associated with oral chronic graft-versus-host-disease (cGVHD). RESULTS: Chronic GVHD is the result of an immune response of donor-derived cells against recipient tissues. Oral cGVHD can affect the mucosa and damage salivary glands and cause sclerotic changes. Symptoms include sensitivity and pain, dry mouth, taste changes, and limited mouth opening. Risk of developing caries and oral cancer is increased. Food intake, oral hygiene, and dental interventions can represent challenges. Oral cGVHD manifestations and dental interventions should be managed in close consultation with the medical team, as systemic treatment for cGVHD can have implications for dental management. CONCLUSIONS: General dental practitioners can contribute substantially to alleviating oral cGVHD involvement and preventing additional oral health deterioration. PRACTICAL IMPLICATIONS: Frequent examinations, patient education, oral hygiene reinforcement, dry mouth management, caries prevention, and management of dental needs are indicated. In addition, oral physical therapy might be needed. Invasive dental interventions should be coordinated with the transplantation team. Screening for oral malignancies is important even years after resolution of GVHD symptoms. Management of the oral manifestations of cGVHD might require referral to an oral medicine professional.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Crônica , Odontólogos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Papel Profissional
11.
J Exp Med ; 217(3): e20192195, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32997932

RESUMO

The cytokine interleukin-22 (IL-22) is a critical regulator of epithelial homeostasis. It has been implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs), and complement production. In this review, we focus specifically on the role of IL-22 in the intestinal epithelium. We summarize recent advances in our understanding of how IL-22 regulates homeostasis and host defense, and we discuss the IL-22 pathway as a therapeutic target in diseases of the intestine, including inflammatory bowel disease (IBD), graft-versus-host disease (GVHD), and cancer.


Assuntos
Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/patologia , Animais , Células Epiteliais/metabolismo , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo
12.
Medicine (Baltimore) ; 99(43): e22781, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120791

RESUMO

RATIONALE: Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for the majority of patients who have malignant haemolytic disease. Although the success rate of HSCT has increased, the increasing number of cases suffering from secondary solid malignancies after HSCT has attracted more interest recently. PATIENT CONCERNS: A 16-year-old female patient from China presented with a crusty and painful lesion on the left buccal mucosa with a history of chronic graft-versus-host disease following allogeneic HSCT for acute myeloid leukaemia. DIAGNOSIS: An incisional biopsy of the lesion showed stratified squamous epithelium mucosa with severe dysplasia (carcinoma in situ). Subsequently, a wide local excision was performed and histological examination revealed early infiltrating squamous epithelial mucosa (carcinoma in situ). INTERVENTIONS: She was being treated in the oral and maxillofacial surgery clinic with an incisional biopsy of the left buccal mucosa. She also received a wide local excision. OUTCOMES: Follow-up for 4 years showed no recurrence. LESSONS: This case helps raise awareness of the diagnosis of oral symptoms in young patients after HSCT. Due to the increasing application of HSCT, raising awareness in oral and dental physicians may be required to improve long-term clinical outcome of patients who underwent HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Bucais/etiologia , Adolescente , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia
13.
Arch. argent. pediatr ; 118(5): e468-e475, oct 2020. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1122525

RESUMO

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


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Doença Enxerto-Hospedeiro/diagnóstico , Manifestações Cutâneas , Transplante Homólogo , Leucemia , Epidemiologia Descritiva , Estudos Retrospectivos , Transplante de Medula Óssea , Exantema
14.
PLoS One ; 15(9): e0238824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915853

RESUMO

Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis on pre-HCT computed tomography (CT) scans may be a marker for development of GVHD and poor outcomes in allo-HCT. In this retrospective study, we reviewed the pre-HCT CT scans and transplant outcome data of patients who underwent allo-HCT at Duke University Medical Center from 2009 to 2017. The presence of steatosis was confirmed using CT attenuation measurements. We then assessed the association between pre-HCT hepatic steatosis and HCT-related outcomes including GVHD. 80 patients who had pre-HCT CT scans were included in the study. Pre-transplant hepatic steatosis was associated with the development of chronic GVHD (OR 4.2, p = 0.02), but was not associated with acute GVHD (OR 1.3, p = 0.7), non-relapse mortality (p = 0.81) or overall survival (p = 0.74). Based on this single center retrospective study, pre-transplant hepatic steatosis is associated with development of chronic GVHD. Further, prospective study with other imaging modalities including non-contrasted CT scans is needed to determine if this association is reproducible.


Assuntos
Fígado Gorduroso/terapia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Transplante Homólogo/efeitos adversos
15.
Rinsho Ketsueki ; 61(8): 953-958, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908060

RESUMO

Expanded human bone marrow-derived mesenchymal stromal/stem cells (MSC) have been used in the treatment of acute graft-versus-host disease (GVHD). It is currently accepted that the use of allogeneic off-the-shelf MSC has therapeutic efficacy with no apparent serious early-onset adverse effects; however, further development would be needed to overcome the current situation of MSC therapy for intractable GVHD. In the emerging recognition of the importance of extracellular vesicles (EV) as modulators of cell-cell communication physiologically and pathologically, we recently revealed that human bone marrow MSC-derived EV ameliorate GVHD clinically and pathologically through the preservation of peripheral naïve T-cell populations in a murine model. In this article, we summarize future perspectives on MSC-based therapy for GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Linfócitos T
16.
Rinsho Ketsueki ; 61(8): 959-964, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908061

RESUMO

Graft-versus-host disease (GVHD) is a potentially life-threatening complication associated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Although prophylaxis and GVHD treatment using immunosuppressants are essential for a successful allo-SCT, profound immunosuppression could lead to an infection and/or the recurrence of malignant diseases. Recently, the concept of tissue tolerance has emerged. This concept has been identified as a means to suppress GVHD by relying on tissue-intrinsic mechanisms that are independent from those underlying immune tolerance. Thus, GVHD prophylaxis and treatments targeting the mechanisms that promote tissue tolerance could help suppress GVHD and maintain leukocyte-mediated immune responses against tumors and infectious pathogens. Epithelial regeneration from LGR5-positive intestinal stem cells and epithelial maintenance mediated by metabolites from the intestinal microbiota are representative mechanisms that promote tissue tolerance in the gut. However, these protective mechanisms are weakened by GVHD and conditioning regimens. This review focuses on the pathophysiology of acute GVHD and tissue-intrinsic mechanisms that promote tissue tolerance.


Assuntos
Doença Enxerto-Hospedeiro , Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Humanos , Condicionamento Pré-Transplante , Transplante Homólogo
17.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 624-629, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942814

RESUMO

Objective: To analyze the clinical characteristics and outcomes of non-aspergillus molds infection (NAMI) patients who underwent allogeneic stem cell transplantation. Methods: Total 24 patients diagnosed as proven or probable non-aspergillus molds infection after allo-HSCT at the Peking University Institute of Hematology from January 2010 to December 2016 were retrospectively reviewed. Results: Among the 24 non-aspergillus molds infection patients, 22 (91.6%) underwent haploidentical stem cell transplantation, while 1 (4.2%) underwent matched-sibling donor transplantation, and 1 (4.2%) underwent HLA-matched unrelated donor transplantation. Ten (41.7%) patients were diagnosed as proven NAMI, and 14 (58.3%) were probable NAMI. The median time to NAMI diagnosis was 188 (2-856) d after transplantation. Five (20.8%) patients had Mucorales infection, 14 (58.3%) Rhizopus infection, 3 (12.5%) had Absidia orchidis infection, and 2 (8.3%) had Scedosporium apiospermum infection. The response rate at was 38.9% (7/18) in 18 patients who adjusted antifungal therapy based on the etiology. After a median 229 (2-2280) days follow-up after diagnosis, the 2-year overall survival was (24.0±14.5) %. Conclusion: The major pathogen of NAMI after allo-HSCT was Rhizopus, and the mortality of NAMI after allo-HSCT was very high due to lack of early effective therapy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções , Micoses/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Irmãos , Transplante Homólogo
18.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 630-636, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942815

RESUMO

Objective: To explore the clinical characteristics, related factors, and prognostic effect of patients with T cell large granular lymphocytosis following allo-HSCT. Methods: Consecutive patients with T-LGL following allo-HSCT who visited our center from June 2013 to February 2020 were studied retrospectively. We compared patients undergoing allo-HSCT during this period. The clinical characteristics, related factors, cumulative incidence of patients with T-LGL and rates of overall survival (OS) , disease free survival (DFS) , relapse, and non-relapse mortality (NRM) were analyzed. Results: Total 359 patients were enrolled, including 17 with T-LGL and 342 without T-LGL following allo-HSCT. The median follow-up duration was 38 (3-92) month. The cumulative incidence at 1-, 2- and 3-years of T-LGL was 3.64% (95%CI 1.09%-6.19%) , 4.50% (95%CI 1.36%-7.64%) , and 4.84% (95%CI 1.10%-8.76%) , respectively. CMV reactivation (P=0.013) , EB viremia (P=0.034) , and aGVHD (P=0.027) were associated with the development of T-LGL following allo-HSCT. Multivariate analysis showed that benign hematologic diseases[P=0.027, OR=3.36 (95%CI 1.15-9.89) ] and haploidentical hematopoietic stem cell transplantation[P=0.030, OR=4.67 (95%CI 1.16-18.75) ], unrelated donor transplantation[P=0.041, OR=5.49 (95%CI 1.10-28.16) ] were independent predictive factors of T-LGL following allo-HSCT. There was a significant difference in the 3-year OS (100.0% vs. 78.6%, P=0.04) , DFS (100.0% vs. 70.0%, P=0.01) , and NRM (0 vs. 12.6%, P=0.02) between the 2 cohorts. Subgroup analysis showed that malignant diseases recipients who developed T-LGL had better outcomes after allo-HSCT, and there was a significant difference in the NRM (P=0.042) , DFS (P=0.013) , and cumulative relapse rate (P=0.028) between the 2 cohorts. In contrast, the appearance of T-LGL after allo-HSCT in patients with benign diseases had no significant effect on the prognosis. Conclusions: T-LGL was a durable and clinically benign phenomenon occurring in allo-HSCT recipients with malignant diseases. Factors associated with immune reconstitution and T-cell regulatory mechanisms might be major predictors of T-LGL following allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Granular Grande , Humanos , Leucemia Linfocítica Granular Grande/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Linfócitos T , Transplante Homólogo
19.
Int J Hematol ; 112(6): 841-850, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32875487

RESUMO

Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.


Assuntos
Beclometasona/uso terapêutico , Cidofovir/uso terapêutico , Etanercepte/uso terapêutico , Foscarnet/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infliximab/uso terapêutico , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Sistema de Registros , Viroses/tratamento farmacológico , Viroses/etiologia , Doença Aguda , Adulto , Doença Crônica , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Transplante Homólogo
20.
Anticancer Res ; 40(10): 5707-5713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988896

RESUMO

BACKGROUND/AIM: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. RESULTS: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. CONCLUSION: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , RNA Longo não Codificante/genética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA