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Although children and adolescents with acute lymphoblastic leukaemia (ALL) have high survival rates, approximately 15-20% of patients relapse. Risk of relapse is routinely estimated at diagnosis by biological factors, including flow cytometry data. This high-dimensional data is typically manually assessed by projecting it onto a subset of biomarkers. Cell density and "empty spaces" in 2D projections of the data, i.e. regions devoid of cells, are then used for qualitative assessment. Here, we use topological data analysis (TDA), which quantifies shapes, including empty spaces, in data, to analyse pre-treatment ALL datasets with known patient outcomes. We combine these fully unsupervised analyses with Machine Learning (ML) to identify significant shape characteristics and demonstrate that they accurately predict risk of relapse, particularly for patients previously classified as 'low risk'. We independently confirm the predictive power of CD10, CD20, CD38, and CD45 as biomarkers for ALL diagnosis. Based on our analyses, we propose three increasingly detailed prognostic pipelines for analysing flow cytometry data from ALL patients depending on technical and technological availability: 1. Visual inspection of specific biological features in biparametric projections of the data; 2. Computation of quantitative topological descriptors of such projections; 3. A combined analysis, using TDA and ML, in the four-parameter space defined by CD10, CD20, CD38 and CD45. Our analyses readily extend to other haematological malignancies.
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Neoplasias Hematológicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Adolescente , Humanos , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Citometria de Fluxo , Imunofenotipagem , RecidivaRESUMO
Polyphenols are a group of chemical substances found in plants, with immunomodulatory, antiproliferative, and anti-inflammatory properties that might be useful in the prophylaxis and treatment of graft-versus-host disease (GVHD). Polyphenolic extract (PE) obtained from extra virgin olive oil (EVOO) decreased the activation and proliferation of activated T cells. In addition, a decreased production of proinflammatory cytokines was observed upon exposure to PE. Western blot assays showed a marked inhibition of Akt phosphorylation and nuclear translocation of NF-κB in activated T cells. In a murine model of acute GVHD, we observed that mice that received a diet supplemented in PE (600 ppm) presented a higher survival rate and lower risk of developing GVHD when compared with the group that received a control diet. Histopathologic examination showed a significantly lower gut involvement in mice receiving PE, with a decrease in proinflammatory cytokines (IL-2, IL-17, and TNF-α) in serum and the reestablishment of butyrate concentration in the gut. In conclusion, PE obtained from EVOO exerted a potent immunomodulatory effect, reducing the activation and proliferation of activated T cells and the production of proinflammatory cytokines. In a murine model of acute GVHD, a PE-supplemented diet reduced the incidence and severity of the disease and increased survival after transplantation.
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Doença Enxerto-Hospedeiro , Animais , Modelos Animais de Doenças , Doença Enxerto-Hospedeiro/prevenção & controle , Camundongos , NF-kappa B , Azeite de Oliva , Extratos VegetaisRESUMO
Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p < .001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; pâ¯=â¯.63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; pâ¯=â¯.001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (pâ¯=â¯.54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; pâ¯=â¯.83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant.
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Seleção do Doador , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doadores não Relacionados , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fatores Imunológicos/administração & dosagem , Inibidores de Proteassoma/administração & dosagem , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de SobrevidaRESUMO
Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.
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Basófilos/patologia , Hemorragia/etiologia , Leucemia Promielocítica Aguda/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem da Célula , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Promielocítica Aguda/complicações , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto JovemRESUMO
OBJECTIVE: MLL gene is involved in more than 80 known genetic fusions in acute leukemia. To study the relevance of MLL partner gene and selected gene's expression, in this work, we have studied a cohort of 20 MLL-rearranged acute myeloid leukemia (AML). METHODS: Twenty MLL-rearranged AML patients along with a control cohort of 138 AML patients are included in this work. By RT-PCR and sequencing, MLL genetic fusion was characterized, and relative gene expression quantification was carried out for EVI1, MEIS1, MLL-3', RUNX1, SETBP1, HOXA5, and FLT3 genes. Risk stratification and association of MLL genetic partner and gene expression to overall survival, in the context of received therapy, were performed. RESULTS: MLLr cohort showed to have an OS more similar to intermediate-risk AML. Type of MLL genetic partner showed to be relevant in allo-HSCT response; having MLLT1 and MLLT3, a better benefit from it. Expression of MLL-3' region, EVI1 and FLT3, showed association with OS in patients undergoing allo-HSCT. CONCLUSION: We show that the MLL genetic partner could have implications in allo-HSCT response, and we propose three genes whose expression could be useful for the prognosis of this leukemia in patients undergoing allo-HSCT: 3' region of MLL, EVI1, and FLT3.
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Regiões 3' não Traduzidas , Biomarcadores Tumorais , Rearranjo Gênico , Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , RNA Mensageiro , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Lactente , Estimativa de Kaplan-Meier , Cariótipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Proteína do Locus do Complexo MDS1 e EVI1/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Prognóstico , Modelos de Riscos Proporcionais , Translocação Genética , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined. Here we have investigated their anti-tumor effect in multiple myeloma (MM). We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells. This effect was mediated by caspase activation, mainly caspase-2, and was partially prevented by a pan-caspase inhibitor. Their pro-apoptotic effect was correlated with an increased expression of Bax and Bak, a decrease of Bcl-xL and Mcl-1, a biphasic response of Akt/PKB and an increase in the levels of ceramide in MM cells. Inhibition of ceramide synthesis partially prevented apoptosis, indicating that these sphingolipids play a key role in the pro-apoptotic effect of cannabinoids in MM cells. Remarkably, blockage of the CB2 receptor also inhibited cannabinoid-induced apoptosis. Cannabinoid derivative WIN-55 enhanced the anti-myeloma activity of dexamethasone and melphalan overcoming resistance to melphalan in vitro. Finally, administration of cannabinoid WIN-55 to plasmacytoma-bearing mice significantly suppressed tumor growth in vivo. Together, our data suggest that cannabinoids may be considered as potential therapeutic agents in the treatment of MM.
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Antineoplásicos/farmacologia , Canabinoides/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Caspase 2/metabolismo , Linhagem Celular Tumoral , Ceramidas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mieloma Múltiplo/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esfingolipídeos/metabolismo , Proteína bcl-X/metabolismoRESUMO
Solitary plasmacytoma represents a heterogeneous group of patients; approximately half develop multiple myeloma (MM) in 2 or 3 years, whereas others remain disease-free at 10 years. By definition, these patients do not have morphologic bone marrow (BM) plasma cell (PC) infiltration. Here, we investigated whether sensitive BM evaluation of patients with solitary bone plasmacytoma (SBP; n = 35) and extramedullary plasmacytoma (EMP; n = 29) through multiparameter flow cytometry (MFC) would unravel the presence of clonal PCs in otherwise disease-free BM, and whether BM clonality predicted higher risk of progression. BM clonal PCs were detected in 17 of 35 SBP (49%) and 11 of 29 EMP (38%) patients. Seventy-one percent of flow-positive vs only 8% of flow-negative SBP patients evolved to MM (median time to progression of 26 months vs not reached; hazard ratio, 17.4; P < .001). No significant differences were observed among EMP cases. Our results highlight the importance of MFC for sensitive BM evaluation of SBP patients, to predict risk of developing treatment-requiring MM and to plan disease monitoring.
Assuntos
Neoplasias Ósseas , Citometria de Fluxo , Mieloma Múltiplo , Plasmocitoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias/métodos , Plasmocitoma/metabolismo , Plasmocitoma/mortalidade , Plasmocitoma/patologia , Plasmocitoma/terapia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Memory B cells (MBCs) have a very long life-span as compared to naïve B cells (NBCs), remaining viable for years. It could predispose them to suffer misbalances in the gene expression pattern at the long term, which might be involved in the development of age-related B-cell disorders. In order to identify genes whose expression might change during life, we analyzed the gene expression patterns of CD27- NBCs versus CD27+ MBCs in young and old subjects. Using microarray assays we observed that the expression pattern of CD27- NBCs versus CD27+ MBCs is significantly different. Furthermore, in order to evaluate the age effect, we compared the gene expression pattern of young versus aged subjects in both cell populations. Interestingly, we did not find significant differences in the CD27- NBC population between young and aged individuals, whereas we found 925 genes differentially expressed in CD27+ MBCs. Among these genes, 193 were also differentially expressed in CD27+ MBCs as compared to CD27- NBCs, most of them involved in cell survival, cell growth and proliferation, cellular development and gene expression. We conclude that gene expression profiles of CD27- NBCs and CD27+ MBCs are different. Moreover, whereas the gene expression pattern of CD27+ MBCs varies with age, the same does not happen in CD27- NBCs. This suggests that MBCs undergo time-dependent changes which could underlie a higher susceptibility to dysfunction with age. This article is protected by copyright. All rights reserved.
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We evaluated the feasibility, safety, and efficacy of the administration of 4 sequential doses (intravenously administered on days 1, 4, 11, and 18) of cryopreserved bone marrow-derived mesenchymal stromal cells (MSC) expanded with platelet lysate and obtained from third-party donors as a second-line treatment for steroid-refractory acute graft-versus-host (aGVHD) disease in a series of 25 patients. All patients received at least 2 doses of MSC, whereas 21 received 3 doses and 18 received the initially planned 4 doses. Because of the achievement of partial response, 4 patients received additional doses of MSC. Median single cell dose administered was 1.1 × 10(6) MSC/kg of recipient body weight. There were no adverse events related to the MSC infusion in the 99 procedures performed, with the exception of a cardiac ischemic event that occurred twice in a patient with prior history of cardiac ischemia. Response to MSC at 60 days after the first dose was evaluable in 24 patients. Seventeen patients (71%) responded (11 complete and 6 partial responses), with a median time to response of 28 days after the first MSC dose, whereas 7 patients did not respond. In summary, we can conclude that sequential cryopreserved third-party MSC therapy administered on days 1, 4, 11, and 18 is a safe procedure for patients with steroid-refractory aGVHD. This strategy may provide a high rate of overall responses of aGVHD with a low toxicity profile.
Assuntos
Criopreservação , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adulto , Antineoplásicos/uso terapêutico , Plaquetas/química , Contagem de Células , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , Esteroides/uso terapêutico , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Doadores não RelacionadosRESUMO
Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.
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[This corrects the article DOI: 10.3389/fimmu.2023.1280580.].
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The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post-transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft-versus-host disease. The cumulative incidence of non-relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non-haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post-transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.
Assuntos
Ácidos Borônicos/uso terapêutico , Mieloma Múltiplo/cirurgia , Transplante de Células-Tronco de Sangue Periférico , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Ácidos Borônicos/farmacologia , Bortezomib , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Terapia Combinada , Ciclosporina/uso terapêutico , Sinergismo Farmacológico , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doenças Hematológicas/induzido quimicamente , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Quimioterapia de Manutenção , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/farmacologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazinas/farmacologia , Indução de Remissão , Reoperação , Terapia de Salvação , Subpopulações de Linfócitos T/efeitos dos fármacos , Transplante Autólogo , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are multipotent stem cells with immunosuppressive properties. Nevertheless, it has been previously reported that MSCs might also trigger the immune response. We studied whether MSCs may act as carriers, capturing antigens that can be endocytosed by antigen-presenting cells later on. METHODS: We measured the cellular uptake of mannose receptor-mediated fluid phase macropinocytosis, assessed as cellular uptake of fluorescein isothiocyanate-dextran, and PKH-67-labeled cell lysates as a surrogate marker for antigen capture among dendritic cells (DCs, positive control), T lymphocytes (negative control) and MSCs. RESULTS: All experiments confirmed that MCSs displayed pinocytic and endocytic capacities, which were lower than those observed for DCs but significantly higher than those observed for T cells. We also demonstrated that MSCs release previously endocytosed antigens, which subsequently can be captured by DCs. CONCLUSIONS: MSCs have the ability to capture and release antigens.
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Endocitose , Antígenos HLA-D/metabolismo , Células-Tronco Mesenquimais/citologia , Pinocitose , Células Apresentadoras de Antígenos/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Antígenos HLA-D/imunologia , Humanos , Imunossupressores , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Receptor de Manose , Lectinas de Ligação a Manose/imunologia , Lectinas de Ligação a Manose/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Multipotentes , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismoAssuntos
Substituição de Aminoácidos , Transplante de Células-Tronco Hematopoéticas , Leucemia de Mastócitos/genética , Leucemia Mielomonocítica Crônica/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Segunda Neoplasia Primária/genética , Mutação Puntual , Proteínas Proto-Oncogênicas c-kit/genética , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Progressão da Doença , Estudos de Associação Genética , Humanos , Cadeias kappa de Imunoglobulina/sangue , Leucemia de Mastócitos/tratamento farmacológico , Leucemia de Mastócitos/patologia , Leucemia de Mastócitos/terapia , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/patologia , Leucemia Mielomonocítica Crônica/terapia , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/genética , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Paraproteínas/análise , Indução de RemissãoRESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.