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2.
Rinsho Ketsueki ; 60(8): 920-923, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484890

RESUMO

A 29-year-old man was diagnosed with acute myeloid leukemia at 20 years of age; he achieved a second complete remission at 22 years of age after an allogeneic unrelated bone marrow transplantation. After 14 months, he developed bronchiolitis obliterans (BO) due to chronic graft-versus-host disease. Home ventilator management was continuously performed for 3 years, but the patient required extracorporeal membrane oxygenation (ECMO) after progression to type 2 respiratory failure. A matched brain-dead lung donor was found after 5 months of intensive care management on ECMO, and bilateral lung transplantation was successfully performed. BO is a progressive refractory respiratory disease with poor prognosis. Careful management of infection, monitoring organ function, and lung transplantation at the appropriate time of initiation of mechanical ventilation or ECMO may save a patient's life. However, it is crucial to collaborate with higher education institutions or medical professionals in other departments.


Assuntos
Bronquiolite Obliterante , Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Adulto , Transplante de Medula Óssea , Humanos , Masculino , Transplante Homólogo , Adulto Jovem
3.
Lancet Haematol ; 6(11): e585-e596, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495699

RESUMO

BACKGROUND: Donors other than matched siblings and low-intensity conditioning regimens are increasingly used in haematopoietic stem cell transplantation. We aimed to compare the relative risk of donor type and conditioning regimen intensity on the transplantation outcomes of in patients with sickle cell disease. METHODS: For this retrospective cohort study, we collected data from 90 US centres reported to the Center for International Blood and Marrow Transplant Research. Eligible patients were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS) or sickle beta thalassemia (Hb Sß), and underwent allogeneic haematopoietic cell transplantation between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient pairs matched at the allele-level (HLA-A, HLA-B, HLA-C, and HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated donors, or mismatched unrelated donors. The main outcome was event-free survival. The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative, and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score, comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow, peripheral blood, or umbilical cord blood), and transplantation period (2008-12 and 2013-17) on outcomes was studied using Cox regression models. FINDINGS: Of 996 patients with sickle cell disease and who underwent transplantation in 2008-17, 910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%] haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched unrelated donors). The median follow-up was 36 months (IQR 18-60) after transplantation from HLA-matched siblings, 25 months (12-48) after transplantation from haploidentical related donors, 37 months (23-60) after transplantation from HLA-matched unrelated donors, and 47 months (24-72) after transplantation from mismatched unrelated donors. Event-free survival was worse in recipients aged 13 years or older than in those younger than 13 years (hazard ratio 1·74, 95% CI 1·24-2·45; p=0·0014) and in those who received a transplant from haploidentical related donors (5·30, 3·17-8·86; p<0·0001), matched unrelated donors (3·71, 2·39-5·75; p<0·0001), and mismatched unrelated donors (4·34, 2·58-7·32; p<0·0001) than in patients who received a transplant from matched siblings. There was no significant difference in event-free survival between recipients of transplants from non-sibling donors: haploidentical related donors (1·43, 0·81-2·50; p=0·21) or mismatched unrelated donors (1·17, 0·67-2·05; p=0·58) versus HLA-matched unrelated donors, or mismatched unrelated donors versus haploidentical related donors (1·22, 0·65-2·27; p=0·98). Event-free survival was also worse in patients conditioned with reduced-intensity regimens (1·97, 1·15-3·36; p=0·013) than in those conditioned with non-myeloablative regimens, but did not differ between those who received myeloablative compared with non-myeloablative regimens (1·57, 0·95-2·61; p=0·079). Interpretation Our data suggest that event-free survival is improved in patients with sickle cell disease who receive an allogenic transplantation at age 12 years or younger and those with an HLA-matched sibling donor. For patients without a matched sibling available for transplantation, our data do not favour one alternative donor type over another in this setting. FUNDING: National Institutes of Health and US Health Services Research Administration, Department of Health and Human Services.


Assuntos
Anemia Falciforme/terapia , Transplante de Medula Óssea , Sangue Fetal/transplante , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Anemia Falciforme/mortalidade , Anemia Falciforme/patologia , Doadores de Sangue , Transplante de Medula Óssea/efeitos adversos , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
4.
Ann Hematol ; 98(10): 2389-2398, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392462

RESUMO

Hematopoietic stem cell transplantation (HSCT) is considered an effective way to prevent relapse in adults with acute lymphoblastic leukemia (ALL). This study aimed to assess general trends in the use of various types of HSCTs performed between 2001 and 2015 in Europe, based on data reported to the European Society for Blood and Marrow Transplantation registry. We also evaluated HSCT rates with respect to ALL incidence in selected countries. Altogether, 15,346 first allogeneic (n = 13,460) or autologous (n = 1886) HSCTs were performed in the study period. Comparing 2013-2015 and 2001-2003, the number of allogeneic HSCTs performed in first complete remission increased by 136%, most prominently for transplantations from unrelated (272%) and mismatched related donors (339%). The number of HSCTs from matched sibling donors increased by 42%, while the total number of autologous HSCTs decreased by 70%. Increased use of allogeneic HSCT was stronger for Philadelphia chromosome (Ph)-positive (166%) than for Ph-negative ALL (38%) and for patients aged > 55 years (599%) than for younger adults (59%). The proportion of allogeneic HSCT with reduced-intensity conditioning (RIC) increased from 6 to 27%. The age-standardized rates of allogeneic HSCT per ALL incidence varied strongly among countries. Our analysis showed a continued trend toward increased allogeneic HSCT use for adults with ALL, which may be attributed to increasing availability of unrelated donors, wider use of RIC regimens, and improving efficacy of pretransplant therapy, including tyrosine kinase inhibitors for Ph-positive ALL. Allogeneic HSCT remains a major tool in the fight against ALL in adults.


Assuntos
Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/tendências , Doadores não Relacionados , Adolescente , Adulto , Fatores Etários , Aloenxertos , Autoenxertos , Transplante de Medula Óssea , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Sociedades Médicas
6.
J Pediatr Orthop ; 39(7): 382-386, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31305383

RESUMO

BACKGROUND: Autologous bone marrow aspirates are utilized to treat various conditions in children. The biological value of bone marrow aspirate depends on the concentration of competent osteoblastic progenitors present in the aspirate. It has been shown in adults that increasing bone marrow aspiration volume beyond 2 mL decreases the concentration of osteoblast progenitor cells because of dilution of the sample with peripheral blood. The effect of varying bone marrow aspiration volumes on the osteoblast cell content has not been determined in children. METHODS: In total, 21 children (3 male and 18 female patients, age range 8 mo to 14 y) scheduled for pelvic osteotomy were included in the study. Three separate bone marrow aspirates of 1, 5, and 10 mL were obtained from the anterior superior iliac crest. Total number of nucleated cells was counted per aspirate and the prevalence of alkaline phosphatase-positive colony-forming units was determined per million nucleated cells. RESULTS: We measured a significant, proportional increase in the total number of nucleated bone marrow precursor cells between the 1 and 5 mL samples (mean±SD, 27±13 and 152±78 million nucleated cells, respectively; P<0.0001). When the aspiration volume doubled from 5 to 10 mL the total number of nucleated cells was 178±76 million (P=0.17). A proportional increase from 2214 alkaline phosphatase-positive colony-forming units in the 1 mL sample to 14,100 alkaline phosphatase-positive colony-forming units in the 5 mL sample was observed. However, the number of colony-forming units per aspirate decreased to 11,880 in the 10 mL sample. CONCLUSIONS: These data demonstrate that in children aspiration up to 5 mL bone marrow from the iliac crest yields a proportional increase in osteoblastic progenitor cells per aspirate. Increasing the aspiration volume beyond 5 mL results in hemodilution, rather than further selection of osteoblastic material. CLINICAL RELEVANCE: These data provide clinicians with a guideline for optimizing aspiration volume of bone marrow in children. LEVEL OF EVIDENCE: Level II-development of diagnostic criteria on basis of consecutive patients.


Assuntos
Células da Medula Óssea , Ílio/citologia , Células-Tronco , Adolescente , Fosfatase Alcalina/análise , Biópsia por Agulha , Medula Óssea , Transplante de Medula Óssea , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Osteoblastos , Sucção
7.
Nat Commun ; 10(1): 3027, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289275

RESUMO

Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or αSMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP+ cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic αSMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.


Assuntos
Fibroblastos/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Neovascularização Fisiológica/fisiologia , Cicatrização/fisiologia , Actinas/genética , Actinas/metabolismo , Animais , Transplante de Medula Óssea , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular , Modelos Animais de Doenças , Fibroblastos/patologia , Fibrose/etiologia , Fibrose/patologia , Proteínas de Fluorescência Verde/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/citologia , Proteína A4 de Ligação a Cálcio da Família S100/genética , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Quimeras de Transplante
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(3): 409-413, 2019 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-31209410

RESUMO

OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is a severe inherited disorder leading to rapid neurological deterioration and premature death. Allogeneic hematopoietic stem cell transplantation (HSCT) is still the only treatment that halts the neurologic symptoms in ALD. However, many patients lack suitable human leukocyte antigen (HLA) matched related donors and must rely on alternative donors for a source of stem cells. The purpose of this study was to explore the outcomes of haploidentical allogeneic stem cell transplantation for ALD patients. METHODS: Between December 2014 and December 2018, eight children with ALD lacking HLA matched related or unrelated donors were treated with haploidentical allogeneic hematopoietic stem cell transplantation. The patients received conditioning regimen with busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg and fludarabine 90 mg/m2. Graft-versus-host disease (GVHD) prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate. RESULTS: All the 8 children received allogeneic stem cell transplants from their fathers. The median age of the recipients was 8 (range: 5-12) years. The median age of the donors was 36 (range: 32-40) years. All the recipients received granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow and peripheral blood-derived stem cells. The median number of total mononuclear cells dose and CD34+ dose was 10.89 (range: 9.40-12.16)×108/kg and 7.06 (range: 0.74-7.80)×106/kg, respectively. Neutrophil engraftment occurred a median of 11 days (range:8-13 days) after transplantation. Platelet engraftment occurred a median of 10 days (range:8-12 days) after transplantation. All the patients achieved complete donor chimerism at the time of engraftment. Four patients had grades II-IV acute GVHD and 1 had chronic graft-versus-host disease. No severe chronic GVHD occurred. Among all the children, 2 had cytomegalovirus (CMV) DNAemia and 2 Epstein-Barr virus (EBV) DNAemia. Overall, seven of them survived and had no major complications related to transplantation. One died of cerebral hernia after epilepsy 125 days after transplantation. CONCLUSION: The preliminary observation demonstrates that haploidentical allogeneic stem cell transplantation with this novel regimen could successfully achieve full donor chimerism in ALD patients. According to our experience, haploidentical allogeneic hematopoietic stem cell transplantation is safe and feasible in the treatment of X-linked adrenoleukodystrophy.


Assuntos
Adrenoleucodistrofia , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adrenoleucodistrofia/terapia , Adulto , Transplante de Medula Óssea , Criança , Pré-Escolar , Cromossomos Humanos X , Humanos , Condicionamento Pré-Transplante
9.
Sultan Qaboos Univ Med J ; 19(1): e15-e18, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31198590

RESUMO

Objectives: Haematopoietic stem cell transplantation (HSCT) in Oman started in 1994 at Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Previous studies have suggested that longer driving time to the transplant centre (DTC) independently correlates with worse overall survival (OS). Therefore, this study aimed to examine the impact of DTC on OS and acute graft-versus-host disease (aGvHD). Methods: This retrospective study included all patients who underwent HSCT between February 2006 and December 2016 at SQUH. The DTC was determined using Google Maps (Google LLC., Mountain View, California, USA). The probability of OS was estimated using a Kaplan-Meier estimator and the impact of DTC on OS was compared using a Cox model. Results: A total of 170 patients were included in this study of which 52% were male and 28% were from the Al Batinah region. The mean age was 14.2 ± 12.2 years. The mean haemoglobin, platelet and white blood cell counts before the HSCT were 10.3 ± 1.7 g/dL, 207 ± 131 × 109/L and 5.1 ± 5.9 × 109/L, respectively. The median DTC for those with aGvHD was 84 minutes, which is similar to patients without aGvHD (P = 0.918). The hazard ratio for DTC as a predictor of OS was 1.0 (P = 0.901). Conclusion: In this single centre study, DTC did not impact aGvHD or OS in patients post-HSCT. The study was limited by its retrospective design and the small sample size. It is recommended that these results be confirmed in a prospective study.


Assuntos
Transplante de Medula Óssea/métodos , Cuidado Transicional/normas , Resultado do Tratamento , Adolescente , Adulto , Transplante de Medula Óssea/normas , Criança , Pré-Escolar , Feminino , Serviços de Assistência Domiciliar/normas , Humanos , Masculino , Omã , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 950-957, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204960

RESUMO

OBJECTIVE: To observe the dynamic changes of hematopoietic reconstitution and multiple lineages differentiation at early phase after transplantation. METHODS: Whole bone marrow mononuclear cells (wBMMNC, 5×106) and enriched c-Kit+ hematopoietic stem/progenitor cells (HSPC, 3×105) from the BM of B6-Ly5.1 mice were transplanted into lethally irradiated B6-Ly5.2 mice, the frequencies and absolute numbers of donor-derived cells (including LKS- and LKS+) were detected by flow cytometry. The multiple lineages differentiation of donor-derived cells was also monitored by flow cytometry. The homing and early phase proliferations of donor-derived cells were observed by two-photon microscope. RESULTS: The donor-derived cells started to proliferation from 5-7 days after transplantation and reached the peak value at 2-3 weeks after wBMMNC transplantation. The donor-derived cells proliferated from 1-2 weeks and maintained until 4 weeks after c-kit+HSPC transplantation. At 1 week after transplantation, the donor-derived cells mainly differentiated into myeloid cells with a few lymphoid cells production (B cells) but the production of T cells was not observed at most in wBMMNC transplanted group, while myeloid cells occupied the majority of donor-derived cells at 2-4 weeks; donor-derived cells almost totally differentiated into myeloid cells at 1-3 weeks after transplantation in c-Kit+ transplanted group and donor-derived B cells appeared at 4 weeks. The absolute number of donor-derived LKS- and LKS+ cells in the BM of c-Kit+ transplanted group were much higher than that of wBMMNC group (P<0.001) at 2 weeks respectively. The clustering proliferation of cKit+ cells at 4-5 days after transplantation was observed by two photon microscope. CONCLUSION: The dynamical rate of proliferation and reconstitution of donor-derived cells are much earlier and quicker in c-Kit+ group than those of wBMMNC group. c-Kit+ cells mainly differentiate into myeloid cells within 1-3 weeks and the lymphoid cell differentiation starts at 4 weeks after transplantation. The immediate proliferation and differentiation of c-Kit+ cells within 1 week maybe due to the urgent needs of hematopoietic regeneration under the myeloablated hosts.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Animais , Transplante de Medula Óssea , Diferenciação Celular , Proliferação de Células , Camundongos , Camundongos Endogâmicos C57BL
11.
Nat Commun ; 10(1): 2882, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253783

RESUMO

NLR Family CARD Domain Containing 5 (NLRC5), an important immune regulator in innate immunity, is involved in regulating inflammation and antigen presentation. However, the role of NLRC5 in vascular remodeling remains unknown. Here we report the role of NLRC5 on vascular remodeling and provide a better understanding of its underlying mechanism. Nlrc5 knockout (Nlrc5-/-) mice exhibit more severe intimal hyperplasia compared with wild-type mice after carotid ligation. Ex vivo data shows that NLRC5 deficiency leads to increased proliferation and migration of human aortic smooth muscle cells (HASMCs). NLRC5 binds to PPARγ and inhibits HASMC dedifferentiation. NACHT domain of NLRC5 is essential for the interaction with PPARγ and stimulation of PPARγ activity. Pioglitazone significantly rescues excessive intimal hyperplasia in Nlrc5-/- mice and attenuates the increased proliferation and dedifferentiation in NLRC5-deficient HASMCs. Our study demonstrates that NLRC5 regulates vascular remodeling by directly inhibiting SMC dysfunction via its interaction with PPARγ.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Túnica Íntima/metabolismo , Animais , Aorta , Apoptose , Pressão Sanguínea , Transplante de Medula Óssea , Proliferação de Células , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Frequência Cardíaca , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Miócitos de Músculo Liso/metabolismo , Plasmídeos , Transcriptoma , Remodelação Vascular
12.
Rinsho Ketsueki ; 60(4): 296-301, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31068559

RESUMO

A 51-year-old man underwent allogeneic bone marrow transplantation (BMT) for recurrent acute myeloid leukemia. Although the patient developed slight edema, pleural effusion, and cardiac effusion 6 months after BMT, his clinical condition improved with furosemide treatment. The patient was transfused with red blood cells for the management of anemia 8 months after BMT. He developed acute respiratory failure with pulmonary alveolar hemorrhage 80 min after the transfusion. He was diagnosed with transfusion-associated circulatory overload (TACO) due to the presence of acute pulmonary congestion and depressed left ventricular systolic function. Reduced circulatory load due to sufficient furosemide led to ventilator weaning 3 days later. Other causes of pulmonary alveolar hemorrhage were excluded, and the patient's condition improved by cardiac failure treatment only. This clinical course indicated that pulmonary alveolar hemorrhage would breakdown the blood vessels due to acute pulmonary congestion. Chemotherapy and prolonged anemia are high risks for cardiac failure in patients with hematological malignancies. Therefore, the possibility of cardiac failure is considered when patients with hematological malignancies have fluid retention, such as cardiac enlargement, edema, and pleural effusion. Moreover, the body fluids should be monitored before and after blood transfusion.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Hemorragia/etiologia , Edema Pulmonar/etiologia , Reação Transfusional , Transfusão de Sangue , Humanos , Masculino , Pessoa de Meia-Idade
13.
Nat Commun ; 10(1): 2189, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097698

RESUMO

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates <40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/análogos & derivados , Inibidores de Janus Quinases/farmacologia , Leucemia Experimental/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Transplante de Medula Óssea , Linhagem Celular Tumoral , Criança , Pré-Escolar , Citarabina/farmacologia , Citarabina/uso terapêutico , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Ensaios de Triagem em Larga Escala/métodos , Humanos , Lactente , Inibidores de Janus Quinases/uso terapêutico , Leucemia Experimental/etiologia , Leucemia Experimental/mortalidade , Leucemia Experimental/patologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Taxoides/farmacologia , Taxoides/uso terapêutico , Irradiação Corporal Total/efeitos adversos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
14.
J Dermatol ; 46(6): 540-543, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31106904

RESUMO

Toxic epidermal necrolysis (TEN) is a rare condition, causing life-threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well-known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53-year-old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi-organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/µL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/imunologia , Síndrome de Stevens-Johnson/imunologia , Evolução Fatal , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/prevenção & controle , Humanos , Enteropatias/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Linfoma/terapia , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Ruptura Espontânea/etiologia , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapia
15.
Ann Hematol ; 98(8): 1973-1980, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111177

RESUMO

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Linfoma/diagnóstico , Linfoma/terapia , Mucosite/diagnóstico , Condicionamento Pré-Transplante/métodos , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , França , Humanos , Linfoma/classificação , Linfoma/mortalidade , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mucosite/patologia , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo
16.
Orv Hetil ; 160(20): 774-779, 2019 May.
Artigo em Húngaro | MEDLINE | ID: mdl-31081358

RESUMO

The relationship between the gut flora and various diseases (obesity, diabetes mellitus, metabolic disorders, allergic and autoimmune diseases, inflammatory bowel diseases, liver failure, infections, certain neuropsychiatric disorders, tumors) has been highlighted in recent years. Depletion of microbiotics inhibits bone marrow healing. Infections and their antibiotic treatment may also affect hematopoiesis. Intestinal flora may also affect the severity of the graft-versus-host disease and may also play a role in the pathogenesis of immunthrombocytopenia through the T-regulator cells. The study summarizes the features of the gut flora, the effects of microbiotics on bone marrow healing, the course of infections, allogeneic bone marrow transplantation, graft-versus-host disease, lymphoma and the results of related research and therapeutic options. The authors briefly discuss the possible linkage between intestinal flora and immunthrombocytopenia and the effectiveness of the immunotherapy of tumors and its effect on the von Willebrand-factor synthesis. They draw attention on the importance of maintaining microbiotics diversity. Orv Hetil. 2019; 160(20): 774-779.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Sistema Digestório/microbiologia , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos
17.
Kardiologiia ; 59(4S): 59-64, 2019 May 24.
Artigo em Russo | MEDLINE | ID: mdl-31131761

RESUMO

We present a 13-years follow-up results in patient with dilated cardiomyopathy. We performed intracoronary infusion of bone marrow mononuclear fraction in patient with 4th heart failure functional class in 2005. We observed an improvement in symptoms (patient had 1st functional class of heart failure) during 10-years follow-up. In 2015 due to clinical worsening we performed 2nd and 3rd bone marrow mononuclear cells infusion with 9-month interval. We observed a signifcant improvement in symptoms, EF and LV sizes. We continue the follow-up.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , Transplante de Medula Óssea , Cardiomiopatia Dilatada/terapia , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Resultado do Tratamento
18.
Nat Commun ; 10(1): 2011, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043609

RESUMO

TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized methylcytosines in DNA. Here we examine the role of TET proteins in regulatory T (Treg) cells. Tet2/3fl/flFoxp3Cre mice lacking Tet2 and Tet3 in Treg cells develop inflammatory disease, and Treg cells from these mice show altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. In littermate mice with severe inflammation, both CD4+Foxp3+ and CD4+Foxp3- cells show strong skewing towards Tfh/Th17 phenotypes. Wild-type Treg cells in mixed bone marrow chimeras and in Tet2/3fl/flFoxp3WT/Cre heterozygous female mice are unable to rescue the aberrant properties of Tet2/3fl/flFoxp3Cre Treg cells. Treg cells from Tet2/3fl/flFoxp3Cre mice tend to lose Foxp3 expression, and transfer of total CD4+ T cells isolated from Tet2/3fl/flFoxp3Cre mice could elicit inflammatory disease in fully immunocompetent mice. Together, these data indicate that Tet2 and Tet3 are guardians of Treg cell stability and immune homeostasis.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Inflamação/imunologia , Proteínas Proto-Oncogênicas/metabolismo , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Transplante de Medula Óssea , Colite , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/transplante , Quimeras de Transplante
19.
Nat Commun ; 10(1): 2220, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101805

RESUMO

Both medullary thymic epithelial cells (mTEC) and dendritic cells (DC) present tissue-restricted antigens (TRA) to thymocytes to induce central tolerance, but the relative contributions of these antigen-presenting cell (APC) subsets remain unresolved. Here we developed a two-photon microscopy approach to observe thymocytes interacting with intact APCs presenting TRAs. We find that mTECs and DCs cooperate extensively to induce tolerance, with their relative contributions regulated by the cellular form of the TRA and the class of major histocompatibility complex (MHC) on which antigen is presented. Even when TRA expression is restricted to mTECs, DCs still present self-antigens at least as frequently as mTECs. Notably, the DC subset cDC2 efficiently acquires secreted mTEC-derived TRAs for cross-presentation on MHC-I. By directly imaging interactions between thymocytes and APCs, while monitoring intracellular signaling, this study reveals that distinct DC subsets and AIRE+ mTECs contribute substantially to presentation of diverse self-antigens for establishing central tolerance.


Assuntos
Tolerância Central/imunologia , Células Dendríticas/imunologia , Timócitos/imunologia , Timo/imunologia , Animais , Apresentação do Antígeno/imunologia , Autoantígenos/imunologia , Autoantígenos/metabolismo , Transplante de Medula Óssea , Separação Celular/métodos , Células Dendríticas/metabolismo , Células Epiteliais/imunologia , Feminino , Citometria de Fluxo/métodos , Microscopia Intravital/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Linfócitos T Reguladores/imunologia , Timócitos/metabolismo , Timo/citologia , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Quimeras de Transplante/imunologia
20.
ACS Appl Mater Interfaces ; 11(17): 15436-15446, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30990301

RESUMO

Phosphate-based glasses (PBGs) are bioactive and fully degradable materials with tailorable degradation rates. PBGs can be produced as porous microspheres through a single-step process, using changes in their formulation and geometry to produce varying pore sizes and interconnectivity for use in a range of applications, including biomedical use. Calcium phosphate PBGs have recently been proposed as orthobiologics, based on their in vitro cytocompatibility and ion release profile. In this study, porous microspheres made of two PBG formulations either containing TiO2 (P40Ti) or without (P40) were implanted in vivo in a large animal model of bone defect. The biocompatibility and osteogenic potential of these porous materials were assessed 13 weeks postimplantation in sheep and compared to empty defects and autologous bone grafts used as negative and positive controls. Histological analysis showed marked differences between the two formulations, as lower trabeculae-like interconnection and higher fatty bone marrow content were observed in the faster degrading P40-implanted defects, while the slower degrading P40Ti material promoted dense interconnected tissue. Autologous bone marrow concentrate (BMC) was also incorporated within the P40 and P40Ti microspheres in some defects; however, no significant differences were observed in comparison to microspheres implanted alone. Both formulations induced the formation of a collagen-enriched matrix, from 20 to 40% for P40 and P40Ti2.5 groups, suggesting commitment toward the bone lineage. With the faster degrading P40 formulation, mineralization of the tissue matrix was observed both with and without BMC. Some lymphocyte-like cells and foreign body multinucleated giant cells were observed with P40Ti2.5, suggesting that this more durable formulation might be linked to an inflammatory response. In conclusion, these first in vivo results indicate that PBG microspheres could be useful candidates for bone repair and regenerative medicine strategies and highlight the role of material degradation in the process of tissue formation and maturation.


Assuntos
Materiais Biocompatíveis/química , Vidro/química , Microesferas , Fosfatos/química , Engenharia Tecidual , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Doenças Ósseas/patologia , Doenças Ósseas/terapia , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Modelos Animais de Doenças , Osteogênese/efeitos dos fármacos , Porosidade , Ovinos , Titânio/química , Microtomografia por Raio-X
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