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1.
Equine Vet J ; 52(1): 144-151, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31120574

RESUMO

BACKGROUND: Allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) could provide multiple advantages over autologous BMDMSCs, including creating an 'off-the-shelf' treatment together with the ability to control for donor variation. OBJECTIVES: The objective of the study was to compare the clinical and synovial fluid response of the normal equine joint to autologous and pooled-allogeneic BMDMSCs while controlling for individual variation and joint variations in response to intra-articular injections. We hypothesised that, by controlling for individual animal and joint variation, we could identify differences between allogeneic vs. autologous BMDMSCs in noninflamed joints. STUDY DESIGN: Randomised-controlled experiment. METHODS: Bone marrow was harvested from eight horses. Autologous BMDMSCs were culture expanded, cryopreserved and thawed immediately prior to administration. For allogeneic BMDMSC treatments, four horses' BMDMSCs were culture expanded, pooled, cryopreserved and thawed immediately prior to use. Ten million (autologous or pooled-allogeneic) BMDMSCs were administered into contralateral forelimb metacarpophalangeal joints so that every autologous and allogeneic injection could be compared within the same animal. Clinical parameters included subjective lameness, objective lameness (Lameness Locator™), response to flexion, joint circumference and joint effusion. Arthrocentesis was performed for assessment of the nucleated cell count, differential cell count, total protein, and synovial concentrations of prostaglandin E2 (PGE2) and c-reactive protein (CRP). All parameters were measured at baseline, 6, 12, 24, 72, 168 and 336 h post-injection. RESULTS: No difference was detected in any parameters between forelimb metacarpophalangeal joints administered autologous or pooled-allogeneic BMDMSCs. MAIN LIMITATIONS: This study did not attempt to measure efficacy of BMDMSCs for musculoskeletal disease and should be followed by properly controlled efficacy trials. CONCLUSIONS: The study did not identify any clinical or cytological differences in the normal joint response to allogeneic or autologous BMDMSCs. A larger study to prove equivalence is warranted as allogeneic BMDMSCs may be a feasible alternative to autologous BMDMSCs.


Assuntos
Células da Medula Óssea , Cavalos , Transplante de Células-Tronco Mesenquimais/veterinária , Células-Tronco Mesenquimais/fisiologia , Animais , Biomarcadores/química , Injeções Intra-Articulares , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Líquido Sinovial , Transplante Autólogo , Transplante Homólogo
2.
Zhonghua Xue Ye Xue Za Zhi ; 40(11): 948-952, 2019 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-31856446

RESUMO

Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion: The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.


Assuntos
Doença Enxerto-Hospedeiro , Biomarcadores , Doença Crônica , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo
3.
Medicine (Baltimore) ; 98(51): e18482, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861030

RESUMO

Allogeneic blood transfusions (ABTs) are common in patients with cancer. The present study investigated the safety of a restrictive ABT strategy in patients with extremity sarcomas.Patients who underwent operations for extremity bone sarcomas between May 2008 and November 2018 were retrospectively reviewed. Clinical outcomes based on hemoglobin concentrations, postoperative infections, and hospital stay were compared between 20 patients who received liberal ABT (control group) and 19 patients who received restrictive ABT (restrictive group). The rates of distant metastasis and death were compared between the groups.The mean number of ABTs was 3.6 ±â€Š3.8 units in the control group and 0.33 ±â€Š0.74 units in the restrictive group (P < .001). Only 3 of 19 patients received transfusions (2 red cell packs each). The hemoglobin levels tended to fall during the first 3 postoperative days but seemed to stabilize within the first postoperative week in both groups. Postoperative surgical site infections only occurred in the patients who received ABTs regardless of the group. The rates of distant metastasis and death were higher in the control group than in the restrictive group (25.0% vs 15.7% and 10.0% vs 0%, respectively), but the differences were not significant.A restrictive ABT strategy may be safely performed in patients with extremity bone sarcomas depending on the intraoperative status and specific characteristics of each patient.


Assuntos
Transfusão de Sangue , Neoplasias Ósseas/cirurgia , Contraindicações , Osteossarcoma/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
4.
Adv Exp Med Biol ; 1189: 267-312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31758538

RESUMO

T cells play a pivotal role in orchestrating immune responses directed against a foreign (allogeneic) graft. For T cells to become fully activated, the T-cell receptor (TCR) must interact with the major histocompatibility complex (MHC) plus peptide complex on antigen-presenting cells (APCs), followed by a second "positive" costimulatory signal. In the absence of this second signal, T cells become anergic or undergo deletion. By blocking positive costimulatory signaling, T-cell allo-responses can be aborted, thus preventing graft rejection and promoting long-term allograft survival and possibly tolerance (Alegre ML, Najafian N, Curr Mol Med 6:843-857, 2006; Li XC, Rothstein DM, Sayegh MH, Immunol Rev 229:271-293, 2009). In addition, costimulatory molecules can provide negative "coinhibitory" signals that inhibit T-cell activation and terminate immune responses; strategies to promote these pathways can also lead to graft tolerance (Boenisch O, Sayegh MH, Najafian N, Curr Opin Organ Transplant 13:373-378, 2008). However, T-cell costimulation involves an incredibly complex array of interactions that may act simultaneously or at different times in the immune response and whose relative importance varies depending on the different T-cell subsets and activation status. In transplantation, the presence of foreign alloantigen incites not only destructive T effector cells but also protective regulatory T cells, the balance of which ultimately determines the fate of the allograft (Lechler RI, Garden OA, Turka LA, Nat Rev Immunol 3:147-158, 2003). Since the processes of alloantigen-specific rejection and regulation both require activation of T cells, costimulatory interactions may have opposing or synergistic roles depending on the cell being targeted. Such complexities present both challenges and opportunities in targeting T-cell costimulatory pathways for therapeutic purposes. In this chapter, we summarize our current knowledge of the various costimulatory pathways in transplantation and review the current state and challenges of harnessing these pathways to promote graft tolerance (summarized in Table 10.1).


Assuntos
Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/citologia , Tolerância ao Transplante , Rejeição de Enxerto , Humanos , Transplante Homólogo
5.
Rinsho Ketsueki ; 60(9): 1120-1130, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597835

RESUMO

Acute myeloid leukemia is a disease that mainly affects older populations, with a median age at diagnosis of 67 years, and outcomes for these patients are poor. Reduced-intensity regimen improves survival after allogeneic hematopoietic cell transplantation (HCT), but this has not been well studied. To reduce non-relapse mortality (NRM) among the elderly, geriatric assessment, HCT-Comorbidity index, and disease risk must be studied before HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Idoso , Humanos , Transplante Homólogo
6.
Rinsho Ketsueki ; 60(9): 1131-1139, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597836

RESUMO

The two main treatment options for patients with higher risk of myelodysplastic syndromes (MDS) are allogeneic hematopoietic stem cell transplantation and azacitidine therapy. Of these, only allogeneic hematopoietic stem cell transplantation is curative, and azacitidine treatment is selected for patients not suitable for transplantation. Compared to conventional treatment with supportive treatment alone or with low dose cytarabine, azacitidine treatment improves survival in MDS patients, even in patients over the age of 75. Because azacitidine treatment takes 4-6 cycles until an initial response, several response-predicting scoring systems have been developed. Novel therapeutic agents and combination therapies of azacitidine with a variety of drugs are currently under study.


Assuntos
Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo
7.
Rinsho Ketsueki ; 60(9): 1148-1156, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597838

RESUMO

The median survival time in myelofibrosis is about 5 years, and allogeneic hematopoietic stem cell transplantation is the only curative treatment. Because the clinical course and prognosis of myelofibrosis is not uniform, transplantation-related death or long-term prognosis should be evaluated by varied prognostic prediction systems. This includes assessing gene mutation information in each patient, and the indication and timing of transplantation should be decided based on this information. Previous reports have shown that transplanted hematopoietic stem cells can be engrafted despite marked fibrosis in the bone marrow, and allogeneic hematopoietic stem cell transplantation is a curative treatment for myelofibrosis. However, the transplant-related mortality rate is 30-50%, and the overall survival rate is only around 50%. Future work should focus on methods to decrease transplant-related mortality, including the selection of stem cell source, the development of optimal pre-transplant treatment, and how to best incorporate JAK2 inhibitors before transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos/terapia , Neoplasias/terapia , Mielofibrose Primária/terapia , Humanos , Transplante Homólogo
8.
Zhonghua Xue Ye Xue Za Zhi ; 40(9): 713-719, 2019 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-31648470

RESUMO

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transfusão de Linfócitos , Linfócitos , Neoplasia Residual , Prognóstico , Transplante Homólogo
9.
Lancet Haematol ; 6(11): e573-e584, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477550

RESUMO

BACKGROUND: The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS: In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. FINDINGS: We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. INTERPRETATION: Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. FUNDING: The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.


Assuntos
Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Estudos Retrospectivos , Sociedades Médicas , Transplante Homólogo
12.
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
13.
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
14.
Rinsho Ketsueki ; 60(8): 968-972, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31484897

RESUMO

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Patients with aggressive ATL exhibit poor outcomes, even with dose-dense intensive chemotherapy. Thus, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered in all patients eligible for transplant. However, patients with aggressive ATL often have chemo-refractoriness or experience early relapse during chemotherapy. Allo-HSCT is often ineffective in patients with active disease status. Mogamulizumab (Moga) was approved in 2012 in Japan as a potent treatment option for patients with relapsed or refractory ATL. However, there is a major concern that the use of Moga before allo-HSCT could increase the risk of post-transplant complications, such as graft-versus-host disease (GVHD), because Moga depletes regulatory T cells. Here, we would like to describe the possible effects of pre-transplant Moga on post-transplant complications, such as acute GVHD, and to discuss how Moga could be efficiently incorporated in the treatment regimen of patients with aggressive ATL to maximize the expected clinical benefit.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Adulto , Humanos , Japão , Receptores CCR4 , Transplante Homólogo
15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(9): 1102-1107, 2019 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-31512450

RESUMO

Objective: To review the current status and progress of sterilization and preservation for allograft in anterior cruciate ligament reconstruction. Methods: The related literature about the sterilization and preservation of allografts in anterior cruciate ligament reconstruction was extensively reviewed and summarized. Results: There are many sterilization methods for allografts, the most commonly used method is γ-ray irradiation, but the optimal irradiation dose is still unclear. Electron beam irradiation is also available, but excessive dose is harmful to graft shaping. A combined sterilization method combining physics and chemistry methods is still being explored. Cryopreservation is the most commonly used method of preservation. In order to reduce the influence of crystals, the principle of "slow cooling and rapid rewarming" should be adhered to as far as possible. Conclusion: The processing methods of allograft can affect the effectiveness of anterior cruciate ligament reconstruction. The clinical doctors should consider the sterilization and preservation methods in practice.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Criopreservação , Esterilização , Transplante Homólogo , Aloenxertos , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Criopreservação/métodos , Humanos , Esterilização/métodos , Transplante Homólogo/métodos
16.
Chemotherapy ; 64(2): 110-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31533095

RESUMO

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Recidiva , Indução de Remissão , Talidomida/uso terapêutico , Transplante Homólogo
17.
Chemotherapy ; 64(2): 57-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484176

RESUMO

Invasive fungal infections are one of the main infectious complications in allogeneic stem cell transplantation (SCT). Triazoles (voriconazole, posaconazole) are the main prophylactic and therapeutic options for the treatment of invasive aspergillosis. However, pharmacological interactions and hepatotoxicity limit its use. Isavuconazole (ISV) is a recently approved azole with a promising interaction and safety profile. We present a case with invasive aspergillosis in the post-allogeneic SCT setting in a critically ill patient with severe multiorgan failure due to veno-occlusive disease. The patient was treated with ISV and B amphotericin during severe kidney and liver failure and multiple immunosuppressants, without significant drug-related toxicity and with favorable outcome. The interaction and safety profile of ISV is discussed along the reported experience. ISV can be an effective salvage therapy even in complex clinical situations with multiple potential interactions.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/terapia , Transplante de Células-Tronco Hematopoéticas , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , DNA Fúngico/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Tórax/diagnóstico por imagem , Transplante Homólogo/efeitos adversos
18.
J Craniofac Surg ; 30(7): 2085-2087, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31490442

RESUMO

INTRODUCTION: Currently, vascularized autologous bone transplantation is considered the gold standard for large mandibular continuity defect reconstruction. Donor site morbidity is a major concern. Therefore, bone tissue engineering (BTE) seems to be the ideal solution. Fresh-frozen bone allograft is the closest material to autologous bone. The purpose of this clinical report is to show a new technique of large mandibular continuity defect reconstruction using a fresh-frozen humeral allograft seeded with autologous iliac bone marrow aspirate and vascularized with a radial forearm flap. METHODS: A 33-year-old man presented with severe cranio-facial trauma resulting in several fractures of the facial skeleton including a comminuted mandibular fracture from left parasymphysis to left angle, which caused a large continuity defect. RESULTS: Result at 6 months was aesthetically and functionally satisfactory with osseointegration of the bone graft. DISCUSSION: The authors chose to use iliac bone marrow aspirate to seed the allograft scaffold since hematopoietic stem cells and mesenchymal stem cell are able to differentiate into osteoblasts, ease of harvest of the iliac crest and its low rate of morbidity. Contemporary biomaterials used for BTE are bioceramic but bone is still the better scaffold to engineer bone and only allografting avoids donor site morbidity. Vascularization is one of the main challenges of BTE; insertion of autologous vascular bundles from pedicle or free flaps is 1 solution. The authors chose the radial forearm flap since the pedicle is long and the authors did not need a great amount of soft tissue.


Assuntos
Medula Óssea , Úmero/cirurgia , Adulto , Transplante Ósseo/métodos , Antebraço/cirurgia , Retalhos de Tecido Biológico , Humanos , Ílio/transplante , Masculino , Mandíbula/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Engenharia Tecidual , Transplante Homólogo
19.
Transplant Proc ; 51(6): 1801-1809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399166

RESUMO

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80-249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.


Assuntos
Vírus BK , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adulto , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Rim/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Carga Viral
20.
Transplant Proc ; 51(6): 2081-2098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399186

RESUMO

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that acts through the members of a family of 5 G protein-coupled receptors (S1P1 to S1P5). Among these, S1P1 is a major regulator of lymphocyte trafficking. Fingolimod, whose active metabolite, fingolimod phosphate, acts as a nonselective S1P-receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating lymphocyte trafficking via downregulation of S1P1 expression on lymphocytes. Here, we describe the pharmacologic profile of a novel S1P1 agonist, ASP1126. ASP1126 preferentially activated S1P1 compared to S1P3 in rat and human guanosine-5'-(γ-thio)-triphosphate (GTPγS) assays. Oral single administration of ASP1126 decreased the number of peripheral lymphocytes and repeated dosing showed a cumulative effect on lymphopenia in both rats and monkeys. ASP1126 prolonged allograft survival in a rat heterotopic heart transplantation model in combination with a subtherapeutic dose of tacrolimus that was independent of drug-drug interactions. In addition, in nonhuman primate (NHP) renal transplantation, pretreatment with ASP1126 reduced not only the number of naive T cells and central memory T cells but also effector memory T cells in the peripheral blood, all of which could contribute to acute graft rejection and prolonged allograft survival in combination with tacrolimus. Further, we confirmed that ASP1126 has a broad ranging safety margin with respect to its effect on lung weight in rats and bradycardia in NHPs, which were the adverse events found in clinical studies of fingolimod. ASP1126 with improved safety profile has the potential to be an adjunct therapy in combination with tacrolimus in clinical transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacologia , Lisofosfolipídeos/agonistas , Esfingosina/análogos & derivados , Aloenxertos/efeitos dos fármacos , Aloenxertos/metabolismo , Animais , Bradicardia/induzido quimicamente , Sinergismo Farmacológico , Humanos , Linfócitos/efeitos dos fármacos , Macaca fascicularis , Masculino , Ratos , Esfingosina/agonistas , Tacrolimo/farmacologia , Transplante Homólogo/métodos
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