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1.
Scand J Immunol ; 95(4): e13143, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35067952

RESUMO

INTRODUCTION: For many patients with primary immune deficiency (PID), stem-cell transplantation (SCT) may be life-saving. OBJECTIVE: To review our experience of 11 years transplanting children with PID in Mexico. METHODS: Chart review of patients who underwent SCT from 2008 to 2018, to describe their diagnoses, time to transplant, conditioning regime, survival rate and outcomes. All patients received post-transplant cyclophosphamide as graft-versus-host-disease (GVHD) prophylaxis. RESULTS: 19 patients with combined, phagocytic or syndromic PID from 5 states. Twelve of them were male (58%) and 14 survive (79%). Mean age at HSCT was 41.9 months; mean time from diagnosis was 31.2 months. Seven grafts were umbilical cord and 12 haploidentical. The conditioning regime was myeloablative, with five primary graft failures. Two patients had partial and 10 full chimerism. Five patients died within 2 months after transplant. Immune reconstitution was complete in 11 of 19 patients. We found a prevalence of 21% GVHD. DISCUSSION: We describe 19 patients from Mexico with 8 PID diagnoses who underwent allogenic HSCT over a period of 11 years. Survival rate and other outcomes compare well with industrialized countries. We recommend the use of post-transplant cyclophosphamide to prevent GVHD in scenarios of resource scarcity and a lack of HLA-identical donors.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária , Criança , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , México , Doenças da Imunodeficiência Primária/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante
2.
J Med Econ ; 25(1): 870-879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35703058

RESUMO

AIMS: Acute respiratory tract infections (ARTIs) are common in hematopoietic stem cell transplantation (HSCT) recipients, however, data is limited regarding epidemiology and economic burden of ARTI in HSCT recipients in Japan. We evaluated the incidence of ARTI in HSCT recipients, associated economic burden, and ARTI-related treatments post-HSCT. MATERIALS AND METHODS: Patients receiving HSCT between July 2017 and December 2018, and those enrolled in the JMDC Claims Database for ≥6 months before index month (month when latest medical procedure code of HSCT recorded) were included. The outcomes included demographics, ARTI incidence, healthcare resource utilization (HCRU), direct costs, and ARTI-related treatments. RESULTS: In 330 analyzed patients, the ARTI incidence rate was 85.5% during total follow-up, consisting of post-HSCT hospitalization of mean 2.1 months and post-discharge periods of mean 17.6 months (post-HSCT hospitalization: 44.8%; post-discharge: 77.6%). For ARTI vs non-ARTI patients during post-HSCT hospitalization, length of hospitalization was significantly longer (mean [SD] months; 2.40 [1.73] vs 1.84 [1.09]; p = 0.0004), and median cost was significantly higher (JPY; 6,250,120.00 vs 4,774,570.00; p = 0.0096). The cost of outpatient visits during post-discharge periods, drug-related and non-drug-related costs of outpatient visits were generally higher for ARTI vs non-ARTI patients. In ARTI vs non-ARTI patients, utilization of any symptom relievers (decongestants, antitussives, and antipyretics), bronchodilators, immunoglobulin G, antibiotics, antivirals, and oxygen supply were numerically higher during post-HSCT hospitalization and post-discharge periods. The proportion of patients and mean prescription days for immunosuppressants during post-HSCT hospitalization were higher in ARTI vs non-ARTI patients. LIMITATIONS: This administrative claims study lacks clinical data and contains only direct medical costs. Patients were retained if they had at least 1 month of enrollment post-HSCT. CONCLUSIONS: In HSCT recipients, ARTI leads to substantial incremental HCRU and direct costs for management in real-world settings in Japan.


People receiving hematopoietic stem cell transplantation (HSCT) commonly suffer from acute respiratory infections (ARTIs). The real-world data on its incidence and economic impact in Japan is limited. In this study, using the JMDC Claims Database 330 HSCT recipients were identified during July 2017 and December 2018. Of these patients, 85.5% developed ARTI either during post-HSCT hospitalization (44.8%, within mean 2.1 months) or post-discharge period (77.6%, within mean 17.6 months). Patients with ARTI had longer hospital stays (2.40 months vs 1.84 months) and higher in-patient treatment costs (6,250,120.00 JPY vs 4,774,570.00 JPY) than those without ARTI. The costs associated with out-patient treatment, both drug-related and non-drug-related, were also higher for ARTI patients than non-ARTI patients. The use of medicines for stuffy nose (decongestants), dry cough (antitussives), and fever (antipyretics), and other medicines to treat respiratory infections (such as bronchodilators, immunoglobulin G, antibiotics, antivirals, and oxygen supply) was generally high with ARTI patients both during post-HSCT hospitalization and during post-discharge periods. The use of immunosuppressants was also more in patients who acquired ARTI as compared with non-ARTI patients during post-HSCT hospitalization. This study demonstrates the significant impact of ARTI in terms of economic and healthcare resource utilization in HSCT recipients in Japan.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Respiratórias , Assistência ao Convalescente , Análise de Dados , Estresse Financeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Japão/epidemiologia , Alta do Paciente , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos
5.
Pathol Oncol Res ; 28: 1610171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755418

RESUMO

The first-line treatment of severe aplastic anemia is allogeneic hematopoietic stem cell transplantation with a matched sibling donor. However, co-morbidities of the identical donor can make donation difficult. We present a transplantation where in parallel with the patient's conditioning treatment, the preparation of the donor with severe hemophilia A required a special management with perioperative factor VIII substitution. Donation was successful without complications, and 18 months after transplantation, the patient and his donor are well without any long-term sequelae. To our knowledge, this is the first reported succesfull transplantation with hemophilic child serving as a bone marrow donor. The procedure did not mean a significant risk to donor health, so donors with hemophilia should not be excluded from donation.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemofilia A , Anemia Aplástica/terapia , Criança , Hemofilia A/complicações , Hemofilia A/terapia , Humanos , Masculino , Irmãos , Condicionamento Pré-Transplante
6.
Anal Cell Pathol (Amst) ; 2022: 3655595, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757015

RESUMO

Breast cancer is considered refractory to immunotherapy. Accordingly, there is an urgent need for the therapeutic use of new immunostimulatory agents which would enhance antitumor immune response against breast cancer cells. "Derived Multiple Allogeneic Protein Paracrine Signaling (d-MAPPS)" is a biological product whose activity is based on chemokines and cytokines that modulate homing and phenotype of immune cells. d-MAPPS contains high concentration of dendritic cell (DC) and T cell-attracting chemokine CXCL16 and potent T cell-activating cytokine IL-27 which enhance DC:T cell cross-talk in inflamed tissues. Herewith, we used 4T1 murine model of breast cancer to analyze d-MAPPS-dependent enhancement of T cell-driven antitumor immunity. 4T1+d-MAPPS-treated mice showed delayed mammary tumor appearance compared to 4T1+saline-treated animals. d-MAPPS significantly reduced tumor weight and volume and improved survival of 4T1-treated mice. Significantly increased concentration of CXCL16, IL-27, IFN-γ, and IL-17 and decreased concentration of immunosuppressive TGF-ß and IL-10 were measured in serum samples and tumor tissues of 4T1+d-MAPPS-treated mice. d-MAPPS enhanced production of IL-12 and increased expression of MHC class II and costimulatory molecules on tumor-infiltrated DC, significantly improving their antigen-presenting properties. d-MAPPS in CXCL16-dependent manner promoted recruitment of antitumorigenic IFN-γ/IL-17-producing CD4+Th1/Th17 cells and in IL-27-dependent manner induced expansion of tumoricidal CD178+granzyme B-expressing CD8+CTLs and inhibited generation of tolerogenic DC, IL-10, and TGF-ß-producing FoxP3-expressing T regulatory cells. In summing up, d-MAPPS, in CXL16- and IL-27-dependent manner, enhanced T cell-driven antitumor immune response and suppressed breast cancer growth in experimental mice.


Assuntos
Neoplasias da Mama , Carcinoma , Transplante de Células-Tronco Hematopoéticas , Interleucina-27 , Animais , Citocinas , Células Dendríticas/metabolismo , Feminino , Humanos , Imunidade , Interleucina-10/metabolismo , Interleucina-17 , Camundongos , Camundongos Endogâmicos BALB C , Comunicação Parácrina , Fator de Crescimento Transformador beta
8.
BMJ Case Rep ; 15(6)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732365

RESUMO

Although patients with multiple myeloma (MM) have improved survival with current therapies, there remains a long-term risk of treatment-associated second primary malignancies. We present a case of a patient with IgG kappa MM undergoing treatment for relapsed disease who was noted to have progressive pancytopenia. For his MM, he had previously undergone autologous stem cell transplant with high-dose melphalan and had received immunomodulatory (IMiD) agents in induction, maintenance and relapse regimens. A peripheral blood smear showed abnormal lymphoid cells, and a bone marrow biopsy revealed B-cell acute lymphoblastic leukaemia (B-ALL). He underwent intensive induction chemotherapy with plans for possible allogeneic stem cell transplant. Secondary B-ALL is a rare occurrence in patients with MM, with exposure to alkylating and IMiD agents being potential risk factors.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Transplante Autólogo
9.
Sci Rep ; 12(1): 10528, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732877

RESUMO

Severe aplastic anemia (SAA) is a life-threatening hematological disorder. The major therapies include matched sibling donor (MSD)- hematopoietic stem cell transplantation (HSCT), matched unrelated donor (MUD)-HSCT and immunosuppressive therapy (IST). However, there are many problems that can occur after HSCT, and graft failure (GF) is one of the most serious complications. To find an effective treatment, we analyzed 10 cases of second HSCT to treat SAA pediatric patients who suffered from GF and concluded that second haploidentical family donors HSCT is an effective treatment. Moreover, adding a small dose of busulfan or 2 ~ 3 Gy total body irradiation (TBI) in nonmyeloablative regimens (NMAs) can promote the engraftment. Although the study also showed that PBSCs, as a source of stem cells, can promote the implantation of neutrophil cells, due to small sample size, more research is still needed.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Criança , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Irmãos , Doadores de Tecidos , Condicionamento Pré-Transplante , Doadores não Relacionados
10.
Front Immunol ; 13: 915590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734165

RESUMO

Measurable residual disease (MRD) positivity before haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an independent prognostic factor in determining outcomes in patients with B-cell acute lymphoblastic leukemia (ALL). In this study, we conducted a parallel comparison of the efficacy and safety in patients with suboptimal MRD response after reinduction who underwent haplo-HSCT after chimeric antigen receptor T-cell (CAR-T) therapy or chemotherapy. Forty B-cell ALL patients who relapsed after first-line chemotherapy and with an MRD ≥0.1% after reinduction were analyzed. The median pre-HSCT MRD in the CAR-T group (n = 26) was significantly lower than that in the chemotherapy group (n = 14) (0.009% vs. 0.3%, p = 0.006). The CAR-T group exhibited a trend toward improved 3-year leukemia-free survival and a significantly improved 3-year overall survival compared to the chemotherapy group [71.8% (95% confidence interval (CI): 53.9-89.6) vs. 44.4% (95% CI: 15.4-73.4), p = 0.19 and 84.6% (95% CI: 70.6-98.5) vs. 40.0% (95% CI: 12.7-67.2), p = 0.008; respectively]. Furthermore, no increased risk of graft-versus-host disease, treatment-related mortality, or infection was observed in the CAR-T group. Our study suggests that CAR-T therapy effectively eliminates pre-HSCT MRD, resulting in better survival in the context of haplo-HSCT.


Assuntos
Linfoma de Burkitt , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Doença Aguda , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva
11.
Biochem Biophys Res Commun ; 617(Pt 1): 42-47, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35675737

RESUMO

Hematopoietic stem cell (HSC) transplantation represents an important curative therapy for numerous hematological and immune diseases. Many efforts have been applied to achieve attainable ex vivo HSC expansion. We previously showed that angiopoietin-like proteins 2 (Angptl2) binds and activates the immune inhibitory receptor human leukocyte immunoglobulin (Ig)-like receptor B2 (LILRB2) to support the expansion of HSC. However, soluble Angptl2 is unstable and the downstream signaling would be attenuated by ligand-binding triggered receptor endocytosis, compromising the potential of Angptl2 to expand HSCs. We proposed that membrane anchored Angptl2 will overcome these limitations. In this study, we constructed the C-terminal and N-terminal anchored membrane Angptl2 (Cm-Angptl2 and Nm-Angptl2) by adding a transmembrane domain at the C-terminal or an anchor sequence at the N-terminal respectively. Both forms of Angptl2 showed efficient expression on the surface of feeder cells. Nm-Angptl2, but not Cm-Angptl2, induces a potent activation of LILRB2 reporter, indicating the fibronectin (FBN) domain at the C-terminus of Angptl2 is essential to stimulate LILRB2 signaling. Compared to soluble Angptl2, Nm-Angptl2 displays higher activities to activate LILRB2 reporter, and to promote the expansion of mouse HSCs as determined by transplantation and limiting dilution assay. Our study revealed the importance of FBN domain for Angptl2 to activate LILRB2 and demonstrated that Nm-Angptl2 have enhanced activities than the soluble protein in LILRB2 activation and HSC expansion, providing a strategy to explore the mode of ligand induced receptor signaling, and an optimized approach to expand HSCs ex vivo.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Proteínas Semelhantes a Angiopoietina/metabolismo , Angiopoietinas/metabolismo , Animais , Células-Tronco Hematopoéticas/metabolismo , Ligantes , Camundongos , Receptores Imunológicos/metabolismo
12.
Orphanet J Rare Dis ; 17(1): 234, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717194

RESUMO

BACKGROUND: Neuronopathic Gaucher Disease (nGD) describes the condition of a subgroup of patients with the Lysosomal Storage Disorder (LSD), Gaucher disease with involvement of the central nervous system (CNS) which results from inherited deficiency of ß-glucosylceramidase. Although systemic manifestations of disease are now corrected by augmentation with macrophage-targeted therapeutic enzyme (enzyme replacement therapy, ERT), neurological disease progresses unpredictably as a result of failure of therapeutic enzyme to cross the blood-brain barrier (BBB). Without therapy, the systemic and neurological effects of the disease progress and shorten life: investigators, principally in Sweden and the UK, pioneered bone marrow transplantation (BMT; Haematopoietic Stem Cell Transplantation HSCT) to supply healthy marrow-derived macrophages and other cells, to correct the peripheral disease. Here we report the first long-term follow-up (over 20 years in all cases) of nine patients in the UK and Sweden who underwent HSCT in the 1970s and 1980s. This retrospective, multicentre observational study was undertaken to determine whether there are neurological features of Gaucher disease that can be corrected by HSCT and the extent to which deterioration continues after the procedure. Since intravenous administration of ERT is approved for patients with the neuronopathic disease and ameliorates many of the important systemic manifestations but fails to correct the neurological features, we also consider the current therapeutic positioning of HSCT in this disorder. RESULTS: In the nine patients here reported, neurological disease continued to progress after transplantation, manifesting as seizures, cerebellar disease and abnormalities of tone and reflexes. CONCLUSIONS: Although neurological disease progressed in this cohort of patients, there may be a future role for HSCT in the treatment of nGD. The procedure has the unique advantage of providing a life-long source of normally functioning macrophages in the bone marrow, and possibly other sites, after a single administration. HSCT moreover, clearly ameliorates systemic disease and this may be advantageous-especially where sustained provision of high-cost ERT cannot be guaranteed. Given the remaining unmet needs of patients with neuronopathic Gaucher disease and the greatly improved safety profile of the transplant procedure, HSCT could be considered to provide permanent correction of systemic disease, including bone disease not ameliorated by ERT, when combined with emerging therapies directed at the neurological manifestations of disease; this could include ex-vivo gene therapy approaches.


Assuntos
Doença de Gaucher , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Nervoso , Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Humanos , Estudos Retrospectivos
15.
Acta Orthop ; 93: 519-527, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642498

RESUMO

BACKGROUND AND PURPOSE: As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS: 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS: At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION: BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.


Assuntos
Neoplasias Ósseas , Substitutos Ósseos , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Neoplasias Ósseas/cirurgia , Criança , Seguimentos , Humanos , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
16.
J Clin Invest ; 132(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35642633

RESUMO

Since researchers first began to uncover the mechanisms underlying allogeneic transplantation, the focus has been on T cells. T cells are a major instigator of graft-versus-host disease (GVHD). The clear association between GVHD occurrence and subsequent reduction in relapse supported concentrating on T cells as the masterminds behind graft-versus-tumor (GVT) effects. Recently, an alternative mediator of GVT has taken center stage: natural killer (NK) cells. Part of the appeal of NK cells is their potential to provide antitumor immunity without GVHD. Donor lymphocyte infusion has been the predominant treatment of relapse after allogeneic transplant, but the mix of lymphocytes includes CD8+ T cells and, consequently, a substantial risk for GVHD. In this issue of the JCI, Shapiro and colleagues developed an adoptive NK cell transfer platform to treat relapse after haploidentical allogeneic transplant. The study demonstrated safety, sought to determine resistance mechanisms, and provided avenues for future research.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais , Recidiva
17.
Trials ; 23(1): 470, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668528

RESUMO

BACKGROUND: The response rate of the first-line therapy with corticosteroid for acute graft versus host disease (aGVHD) is about 50%, and steroid-refractory disease is associated with high mortality. The improved response rate to the first-line therapy of newly diagnosed aGVHD patients would result in therapeutic benefits. Ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, has been approved for the treatment of steroid-refractory acute GVHD. The addition of ruxolitinib to the first-line therapy may improve the efficacy of corticosteroids. METHODS: This investigator-initiated, open-label, multicenter, prospective randomized, and controlled two-arm phase II study compares the efficacy and safety of ruxolitinib combined with 1 mg/kg methylprednisolone versus 2 mg/kg methylprednisolone alone in newly diagnosed aGVHD patients. Patients with intermediate or high-risk aGVHD, as defined by the Minnesota aGVHD high-risk score and biomarker algorithm, are eligible for this study. A total of 198 patients will be randomized at a 1:1 ratio and assigned a GVHD risk (intermediate versus high risk) and disease status before transplantation (complete remission versus no complete remission). The primary endpoint is the overall response rate on day 28, which is defined as an improvement of at least one stage in the severity of aGVHD in one organ without deterioration in any other organ or disappearance of any GVHD signs from all organs without requiring new systemic immunosuppressive treatment. The secondary objectives consist of response time, response duration, overall survival, disease-free survival, non-relapse mortality, failure-free survival, and changes in serum levels of proinflammatory cytokines and GVHD-related biomarkers. DISCUSSION: This open-label, multicenter, two-arm randomized trial will evaluate whether the addition of ruxolitinib combined with corticosteroid is superior to corticosteroid alone in newly diagnosed high-risk aGVHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04061876 (version number: 2019.5.18). Registered on July 16, 2019.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Corticosteroides/efeitos adversos , Biomarcadores , Ensaios Clínicos Fase II como Assunto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Metilprednisolona/efeitos adversos , Estudos Multicêntricos como Assunto , Nitrilas , Estudos Prospectivos , Pirazóis , Pirimidinas , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/uso terapêutico
18.
J Immunol Res ; 2022: 6572338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669103

RESUMO

Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney.


Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Biomarcadores , Humanos , Rim , Transplante de Rim/efeitos adversos , Lipocalina-2 , Qualidade de Vida
20.
Zhonghua Xue Ye Xue Za Zhi ; 43(5): 400-407, 2022 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-35680598

RESUMO

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacologia , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Células Matadoras Naturais , Estudos Retrospectivos , Resultado do Tratamento
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