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1.
Khirurgiia (Mosk) ; (9): 69-74, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33030004

RESUMO

Critical limb ischemia, especially in the absence of autologous vein, prosthetic and native vascular infections are isolated diseases for which there currently doesn't have best surgical treatment. Vascular allografts may be the treatment of choice for these patients. In this analysis, we tried to reflect the directions of development of vascular allotransplantation, global trends related to indications for their use, methods of conservation, degradation and endothelial dysfunction. At the present time there doesn't have meta-analyzes on the efficiency of using arterial allografts or other options for implantation (synthetic graft, xenografts) for critical limb ischemia and graft and native infections. Now it is wrong to recommend using them always. Further studies of their performance are necessary. In addition, development of graft control techniques is also needed when rejection develops. Currently, there are no special diagnostic markers, the assessment of which could save patients with immune-mediated dilatation and dysfunction of allografts.


Assuntos
Artérias , Procedimentos Cirúrgicos Reconstrutivos , Aloenxertos , Humanos , Extremidade Inferior , Transplante Homólogo
4.
Rinsho Ketsueki ; 61(8): 945-952, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908059

RESUMO

Human herpesvirus (HHV)-6B encephalitis has been increasingly recognized as an important central nervous system (CNS) complication after allogeneic hematopoietic stem cell transplantation. In this review, the best way to diagnose and treat this devastating complication is described. Diagnostic pitfalls: HHV-6B encephalitis should be diagnosed based on the presence of CNS symptoms, positive results for HHV-6 DNA in the cerebrospinal fluid (CSF), and exclusion of other causes of CNS symptoms. There are potential pitfalls when diagnosing HHV-6B encephalitis. Moreover, false-positive detection of HHV-6 DNA in the CSF can occur. Pleocytosis is observed in few patients, and CSF protein levels are often normal. Limbic encephalitis findings are not commonly detected through a brain MRI at the time of development. Prevention: Neither routine monitoring nor routine prophylactic antiviral therapy is recommended to prevent the development of HHV-6B encephalitis. Treatment: Empiric therapy should be started immediately after HHV-6B encephalitis is suspected. The Guideline Committee of the JSHCT recommends full-dose foscarnet (180 mg/kg/day) for the treatment of HHV-6B encephalitis. Therapeutic effect of anti-HHV6 therapy is assessed based on CNS symptoms and HHV-6 DNA in the CSF, which should be evaluated 1-2 weeks after initiating treatment. Even in patients exhibiting good therapeutic effects, antiviral treatment should be continued for at least 3 weeks.


Assuntos
Encefalite Viral , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Infecções por Roseolovirus , Foscarnet , Humanos , Transplante Homólogo
5.
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
6.
Rinsho Ketsueki ; 61(8): 971-978, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908063

RESUMO

The event-free survival rate for childhood acute myeloid leukemia (AML) is approaching 60%, owing to the use of intensive chemotherapy, optimal indication of hematopoietic stem cell transplantation, and advances in supportive care. For further improvement, the development of more definitive risk stratification system and introduction of more effective treatment options are necessary. Recently, much attention has been drawn on minimal residual disease (MRD) that is considered a strong prognostic factor for children with AML. Recent studies from the United States and Europe have shown the prognostic impact of FCM-based MRD detection and it is already used for risk stratification in modern AML protocols. Myeloid leukemia in Down's syndrome (ML-DS) has unique characteristics, and ML-DS children are recently being treated separately from non-DS AML children with less intensive treatment. It has been shown that relapsed and refractory cases of ML-DS are difficult to treat; however, no universal prognostic factor has been found yet. In order to determine accurate methods for identifying a subgroup with poor prognosis, an attempt to analyze the role of MRD had been examined in the JPLSG AML-D11 study. In this study, the MRD by FCM and targeted deep sequencing for GATA1 after initial induction therapy were significant prognosis factors for predicting relapse.


Assuntos
Leucemia Mieloide Aguda , Criança , Europa (Continente) , Transplante de Células-Tronco Hematopoéticas , Humanos , Neoplasia Residual , Transplante Homólogo
7.
Medicine (Baltimore) ; 99(33): e21752, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872067

RESUMO

RATIONALE: As the major complications post allogeneic hematopoietic stem cell transplantation (allo-HSCT), gastrointestinal disorders were most commonly ascribed to acute graft-versus-host disease (aGVHD) and opportunistic infections. Though Giardia lamblia (G lamblia) is the most common waterborne parasite of intestinal infection worldwide, seldom has it been reported in a patient with acute severe aplastic anemia after allo-HSCT. PATIENT CONCERNS: A 23-year-old male with severe aplastic anemia developed diarrhea, abdominal cramps, bloating, nausea, vomiting, fever, weight loss, and fatigue after allo-HSCT. DIAGNOSIS: Stool examinations for ova and parasites showed Giardia trophozoites and cysts. INTERVENTIONS: Methylprednisolone was stopped and the patient was intravenously treated with a 7-day course of metronidazole (500 mg, tid.). Simultaneously, cyclosporine (5 mg/kg) was continually utilized for suspicious gut GVHD. OUTCOMES: The Giardia lamblia in stool turned negative and his symptoms were resolved after the 7-day course. LESSONS: Incorporating non-invasive monitoring of stool examination for ova and parasites in the follow-up algorithm for post-HSCT patients can expedite clinical decision-making in the differential diagnoses for aGVHD even in the non-endemic area. Metronidazole therapy can be well-tolerated in HSCT patients with giardiasis.


Assuntos
Giardia lamblia/isolamento & purificação , Giardíase/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Diagnóstico Diferencial , Humanos , Masculino , Transplante Homólogo , Adulto Jovem
8.
Blood Adv ; 4(17): 4147-4150, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32886750

RESUMO

Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.


Assuntos
Antígenos CD34/análise , Criopreservação , Células-Tronco Hematopoéticas/citologia , Sobrevivência Celular , Infecções por Coronavirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Transplante Homólogo
9.
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
10.
Anticancer Res ; 40(10): 5909-5917, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988922

RESUMO

BACKGROUND/AIM: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. PATIENTS AND METHODS: In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. RESULTS: We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. CONCLUSION: Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.


Assuntos
Acetatos/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/administração & dosagem , Adulto , Idoso , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Replicação Viral/efeitos dos fármacos
11.
J Heart Lung Transplant ; 39(9): 894-903, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32891266

RESUMO

BACKGROUND: Orthotopic heart transplantation (OHT) recipients may be particularly vulnerable to coronavirus disease 2019 (COVID-19). OHT during the pandemic presents unique challenges in terms of feasibility and safety. METHODS: Chart review was performed for consecutive OHT recipients with COVID-19 and waitlisted patients who underwent OHT from March 1, 2020 to May 15, 2020. RESULTS: Of the approximately 400 OHT recipients followed at our institution, 22 acquired COVID-19. Clinical characteristics included median age 59 (range, 49-71) years, 14 (63.6%) were male, and median time from OHT to infection was 4.6 (2.5-20.6) years. Symptoms included fever (68.2%), gastrointestinal complaints (55%), and cough (46%). COVID-19 was severe or critical in 5 (23%). All patients had elevated inflammatory biomarkers. Immunosuppression was modified in 85% of patients. Most (n = 16, 86.4%) were hospitalized, 18% required intubation, and 14% required vasopressor support. Five patients (23%) expired. None of the patients requiring intubation survived. Five patients underwent OHT during the pandemic. They were all males, ranging from 30 to 59 years of age. Two were transplanted at United Network of Organ Sharing Status 1 or 2, 1 at Status 3, and 2 at Status 4. All were successfully discharged and are alive without allograft dysfunction or rejection. One contracted mild COVID-19 after the index hospitalization. CONCLUSION: OHT recipients with COVID-19 appear to have outcomes similar to the general population hospitalized with COVID-19. OHT during the pandemic is feasible when appropriate precautions are taken. Further study is needed to guide immunosuppression management in OHT recipients affected by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Rejeição de Enxerto/prevenção & controle , Insuficiência Cardíaca/cirurgia , Transplante de Coração/métodos , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Pneumonia Viral/complicações , Idoso , Infecções por Coronavirus/epidemiologia , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento
12.
Bull Cancer ; 107(9): 925-933, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32921398

RESUMO

Sickle cell disease is associated with severe complications and early mortality in adults. In children, hematopoietic stem cell transplant from HLA-identical sibling can stop the progression of the disease and leads to more than 95% long-term free survival without sickle cell disease. The aim of this workshop was to define indications and modalities of allogeneic hematopoietic stem cell transplant in children and adults with sickle cell disease. Patient and sibling HLA typing should be proposed, early in the course of the disease, when intensification therapies are required. Indications of transplant from HLA-identical sibling in children and adults are, cerebral vasculopathy, occurrence of vaso-occlusive events despite hydroxycarbamide, renal and hepatic diseases related to SCD, chronic anemia<7g/dL despite hydroxycarbamide, need to maintain transfusion programs longer than six months, and major transfusion difficulties related to red blood cell alloimmunization. In children with an HLA-identical sibling donor, we recommend a myeloablative conditioning regimen associating high dose busulfan, cyclophosphamide and ATG, considering the excellent results of this approach In patients over 15 years of age, we recommend the NIH approach consisting of a reduced intensity conditioning regimen by alemtuzumab, and 3Gy total body irradiation, followed by peripheral hematopoietic stem cells and post-transplant immunosuppression by sirolimus In the absence of HLA-identical sibling donor, there is no definitive data for preferring transplant from unrelated versus haplo-identical donors but we recommend to evaluate these approaches in prospective trials.


Assuntos
Anemia Falciforme/cirurgia , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Humanos , Transplante Homólogo
13.
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
14.
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
15.
Medicine (Baltimore) ; 99(35): e22064, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871966

RESUMO

RATIONALE: Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion. PATIENT CONCERNS: A 25-year-old male with AML experienced relapse 9 months after allo-HSCT. DIAGNOSIS: Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease. INTERVENTIONS: Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/µl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0. OUTCOMES: His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy. LESSONS: GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Gemtuzumab/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adulto , Humanos , Masculino , Recidiva , Transplante Homólogo
18.
Virology ; 548: 168-173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32838938

RESUMO

Clinical significance of the cytomegalovirus (CMV) genotypes in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) has been evaluated mostly in adults. The studies of diverse CMV glycoprotein B (gB) and N (gN) genotype variants in transplanted children and adolescents are lacking. We analyzed the investment of gB and gN genotype variants in the HSCTed children and their relation to clinical complications and disease outcome. The cohort included forty two pediatric recipients of the HSCT. Patients positive for CMV DNAemia (24/42, 57.1%) were genotyped. The gB4 and gN1 genotype variants predominated and were evidenced in 7/18 (38.9%) and 9/19 (47.4%) patients, respectively. The graft-versus-host disease (GvHD) predominated in children with viremia (p < 0.05). Frequencies of the gB and gN genotypes contrasted those reported in recent studies. The GvHD scaled strongly with CMV reactivation whereas viral loads were uncorrelated to medical complications and treatment outcomes.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/virologia , Proteínas do Envelope Viral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Citomegalovirus/classificação , Citomegalovirus/genética , Citomegalovirus/metabolismo , Feminino , Genótipo , Doença Enxerto-Hospedeiro/virologia , Humanos , Masculino , Transplante Homólogo/efeitos adversos , Proteínas do Envelope Viral/metabolismo , Adulto Jovem
19.
Rev Med Suisse ; 16(701): 1428-1431, 2020 Aug 05.
Artigo em Francês | MEDLINE | ID: mdl-32833358

RESUMO

Meniscectomy in a young active patient can lead to poor outcomes with pain, decreased function and long-term osteoarthritis. Meniscal allograft transplantation (MAT) has therefore been developed to address this issue. We now have 30 years of experience with this technique which is no longer considered experimental and new indications have been added. MAT allows restoration of joint biomechanics, pain relief, improvement in knee function and stability, and reduce cartilage degeneration. This is a comprehensive review of the role of menisci, the indications and principles of MAT, as well as these results.


Assuntos
Menisco/transplante , Transplante Homólogo , Humanos , Articulação do Joelho/cirurgia , Meniscectomia , Menisco/cirurgia , Resultado do Tratamento
20.
Nat Commun ; 11(1): 4227, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839441

RESUMO

In hematopoietic cell transplants, alloreactive T cells mediate the graft-versus-leukemia (GVL) effect. However, leukemia relapse accounts for nearly half of deaths. Understanding GVL failure requires a system in which GVL-inducing T cells can be tracked. We used such a model wherein GVL is exclusively mediated by T cells that recognize the minor histocompatibility antigen H60. Here we report that GVL fails due to insufficient H60 presentation and T cell exhaustion. Leukemia-derived H60 is inefficiently cross-presented whereas direct T cell recognition of leukemia cells intensifies exhaustion. The anti-H60 response is augmented by H60-vaccination, an agonist αCD40 antibody (FGK45), and leukemia apoptosis. T cell exhaustion is marked by inhibitory molecule upregulation and the development of TOX+ and CD39-TCF-1+ cells. PD-1 blockade diminishes exhaustion and improves GVL, while blockade of Tim-3, TIGIT or LAG3 is ineffective. Of all interventions, FGK45 administration at the time of transplant is the most effective at improving memory and naïve T cell anti-H60 responses and GVL. Our studies define important causes of GVL failure and suggest strategies to overcome them.


Assuntos
Apresentação do Antígeno/imunologia , Efeito Enxerto vs Leucemia/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia/terapia , Linfócitos T/imunologia , Animais , Células Cultivadas , Humanos , Leucemia/imunologia , Leucemia/patologia , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/imunologia , Antígenos de Histocompatibilidade Menor/metabolismo , Recidiva , Transplante Homólogo
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