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BACKGROUND: KIR/HLA mismatch in hematopoietic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia (AML), was related to decreased recurrence rates, improved engraftment, and a reduction in graft-versus-host disease, according to recent research (GVHD). Uncertainty exists about the impact of KIR/HLA mismatch on haploidentical-HSCTs treated with post-transplant cyclophosphamide (PTCy). We attempted to analyze the effects of KIR/HLA mismatch on clinical outcomes on transplant outcomes using the cohort of 54 AML patients who received a haplo-HSCT with PTCy. RESULTS: In contrast to KIR/HLA match, our findings showed that donor KIR/HLA mismatch was substantially associated with superior OS (HR, 2.92; (P = 0.04)). Moreover, donor KIR/HLA mismatch (KIR2DS1D/C2+ R and KIR2DS2D/C1+ R mismatch versus KIR2DL1D/C2- R mm, KIR2DL2/3D/C1- R mm and KIR3DL1D/Bw4- mm) was correlated with the improvements in OS (HR, 0.74; P = 0.085) and activating. KIR/HLA mismatch versus KIR/HLA match was significantly correlated with improvements in OS (HR, .46; P = 0.03) and inhibitory. KIR/HLA mismatch versus KIR/HLA match was enhancement in the OS (HR, .93; P = 0.06). Despite a higher rate of aGvHD (grade I-IV) in the patients with KIR/HLA mismatch compared to KIR/HLA matched (57% vs. 33% (p = 0.04). However, the KIR/HLA mismatch group saw a decreased relapse rate (3.2% vs. 23%, p = 0.04). CONCLUSION: This analysis shows the significance of KIR/HLA Incompatibility, other clinical variables like CMV, the relationship between donor/recipient and donor age, and the relationship between donor/recipient and donor age in the haplo-donor selection process. It also suggests that KIR and HLA mismatching between donor and recipient could be routinely performed for haplo-donor selection and may improve clinical outcomes after haplo-HSCTs with PTCy.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida/uso terapêutico , Leucemia Mieloide Aguda/terapia , Linfócitos T , Doença Enxerto-Hospedeiro/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVE: This review aimed to summarize the available data and offer a practical recommendation regarding the optimal regimen of levetiracetam (LEV) for the prevention of busulfan-induced seizure (BIS) in patients undergoing hematopoietic stem cell transplantation (HSCT). DATA SOURCES: Published articles by searching databases (PubMed, Google Scholar, Cochrane Library, ScienceDirect) were reviewed. All types of original studies performed in pediatric and adult populations have been investigated and required data was extracted. DATA SUMMARY: Eleven articles were eligible to be included in this review. A loading dose was not used in any of the studies. LEV had been started from 6 to 48 h before busulfan (Bu) initiation and continued up to 24 to 48 h after its termination. The dose range of LEV was 10 to 20â mg/kg/day divided every 12 h in pediatrics and 500 to 1000â mg twice daily in adults. Both oral and intravenous (IV) routes of administration were used. Except for three studies, no seizure had occurred in patients who had received LEV. CONCLUSIONS: Considering the available evidence, LEV with the dose range from 500 to 1000â mg twice daily in adults and 10â mg/kg twice daily (20â mg/kg/day in 2 divided doses) in children orally or IV started from 6 to 24 h before Bu initiation up to 24 to 48 h after the last dose of Bu seems to prevent BIS appropriately. More prospective clinical trials with a larger population are needed to validate the optimal dosing of LEV for BIS prophylaxis in patients undergoing HSCT.
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Bussulfano , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Bussulfano/efeitos adversos , Levetiracetam , Estudos Prospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/prevenção & controle , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Bone marrow transplantation is the only curative treatment for beta-thalassemia major. Data on the co-transplantation of MSCs with HSCs in beta-thalassemia major patients are scarce. We aimed to investigate the outcomes of thalassemia major patients who underwent bone marrow-derived MSC co-transplantation with HSCs compared with those who only received HSCs. This prospective randomized study included patients with class III thalassemia major undergoing HSCT divided randomly into two groups: Thirty-three patients underwent co-transplantation of bone marrow-derived MSCs with HSCs, and 26 patients only received HSCs. Five-year OS, TFS, TRM, graft rejection rate, and GVHD were estimated. The 5-year OS was 66.54% (95% CI, 47.8% to 79.9%) in patients who underwent co-transplantation of MSCs with HSCs vs 76.92% (95% CI, 55.7% to 88.9%) in patients who only received HSCs (P = .54). No significant difference was observed in the 5-year TFS between the two groups (59.1% vs 69.2%; P = .49). The 5-year cumulative incidence of TRM was not statistically significant among patients who underwent co-transplantation of MSCs with HSCs (27.27%) vs those who only received HSCs (19.23%; P = .61). There was no statistically significant difference in graft rejection, acute GvHD, and chronic GvHD between the two groups. Based on our findings, the co-transplantation of MSCs and HSCs to class III thalassemia major patients does not alter their transplantation outcomes including OS, TFS, rejection rate, transplant-related mortality, and GvHD.
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Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Talassemia beta/terapia , Adolescente , Criança , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Talassemia beta/classificaçãoRESUMO
Allogeneic hematopoietic stem cell transplantation (HSCT) currently is the only available curative option for transfusion-dependent thalassemia. Peripheral blood is a more convenient source for HSCT in comparison with bone marrow. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them. The aim of this study was to evaluate the pros and cons of using peripheral blood instead of bone marrow as the graft source in thalassemia transplantation. We analyzed the transplant results of 567 transfusion-dependent thalassemia patients who received a transplant between 1998 and 2015 considering their stem cell source as a comparative variable. In multivariate Cox analysis the survival advantage for bone marrow compared with peripheral blood was not significant after adjusting for sex, age, and hepatic fibrosis presence. Rejection incidence was significantly lower in patients who used peripheral blood as their graft source. Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants, but the difference was not statistically significant. This study shows that peripheral blood could be an alternative stem cell source in patients undergoing allogeneic HSCT for thalassemia.
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Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Talassemia beta/mortalidade , Talassemia beta/terapia , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Maroteaux-Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux-Lamy syndrome using non-sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other-related (n=1), full-matched other-related (n=1), and one-locus-mismatched unrelated donor. Stem cell sources included bone marrow (n=1), peripheral blood (n=1), and cord blood (n=1). Currently, two patients who received transplant from other-related donors showed full engraftment and regression of the symptoms of the disease, while for the patient with unrelated cord blood donor, graft failure resulted in progression of the disease and death. The result of our study showed beneficial effects of HSCT even from heterozygote donor. Due to rarity of the disease, future multicenter studies are recommended to find the best treatment approaches based on the patients' status.
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Transplante de Células-Tronco Hematopoéticas/métodos , Mucopolissacaridose VI/terapia , Condicionamento Pré-Transplante/métodos , Criança , Pré-Escolar , Evolução Fatal , Feminino , Humanos , MasculinoRESUMO
While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.
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Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Humanos , Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodosRESUMO
BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.
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Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Feminino , Masculino , Condicionamento Pré-Transplante/métodos , Pré-Escolar , Transplante Homólogo/métodos , Adolescente , Rejeição de Enxerto , Doença Aguda , Transplante Autólogo , Lactente , Leucemia Mieloide Aguda/terapiaRESUMO
Over the past 3 decades numerous studies have reported an association between systemic lupus erythematosus (SLE) and thyroid cancers. However, there has been no scientometric analysis in this area of research. To perform a comprehensive scientometric analysis of the global literature published on the association between SLE and thyroid cancers. The data on publications within thyroid cancers in SLE patients were retrieved from the Scopus database using a defined search strategy from its first publication in 1964 to 2023. To conduct a collaboration mapping analysis among keywords, authors, journals, and territories, VOSviewer was utilized. Our final research resulted in 246 scientific publications with 8072 citations, which were published in 198 journals affiliated to 48 countries. A global upward trend has been observed in the last 20 years, with the highest number of publications in the year 2022 (nâ =â 28; 11.4%). The United States led the global productivity ranking with 74 publications (30.1%), followed by China with 25 publications (10.2%). The most popular journals in this field were "Arthritis Research and Therapy" and "Frontiers in Endocrinology," while the most co-cited journal was "Autoimmunity Reviews." The top 3 most prolific authors were Bernatsky, S., Clarke, A.E., and Ramsey-Goldman, R with 9 publications each. This first scientometric study comprehensively offered an overview of the status of thyroid cancers in SLE patients, assessing scholarly productivity in this domain over a period of 50 years.
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Bibliometria , Lúpus Eritematoso Sistêmico , Neoplasias da Glândula Tireoide , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Neoplasias da Glândula Tireoide/epidemiologia , Pesquisa Biomédica/tendências , Saúde Global , Publicações Periódicas como AssuntoRESUMO
Objectives: Fanconi anemia (FA) is a rare, heterogeneous, inherited disorder. Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis. This study reports the outcomes of FA-HSCT patients and identifies factors, including clinical phenotype. Our team examined more than 95% of Iranian FA patients during the last decade. Study Design: One hundred and six FA patients (age range: 2-41) who underwent HSCT from March 2007 to February 2018 were enrolled. Clinical characteristics of genetic disease, pre-HSCT findings, HSCT indication, and long-term follow-up evaluated and recorded. Data were analyzed using SPSS 19.0. Results: The mean follow-up period for survivors was 36 months (range, 1-101). The 3-year overall survival (OS) and disease-free survival were 72.2% and 71.2%, respectively. The 3-year OS rate for patients with limited and extensive malformations was 78.8% and 56.6%, respectively (p = 0.025). Acute graft versus host disease incidence was 60.52% for patients with limited malformations versus 70% for patients with extensive ones (p = 0.49). Chronic graft versus host disease incidence for these two groups was 9.21% and 10%, respectively (p = 0.91). Conclusions: OS was not associated with each of the malformations singly; however, it was lower in the extensive group. The younger age of patients at the HSCT time leads to a higher OS. The differences in FA patients' outcomes and the various genotypes were probably related. These data provide a powerful tool for further studies on genotype-phenotype association with HSCT results.
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Natural killer (NK) cell behavior and function are controlled by a balance between negative or positive signals generated by an extensive array of activating and inhibiting receptors, including killer cell immunoglobulin-like receptor (KIR) proteins, main components of the innate immune system that contribute to initial responses against viral infected-transformed cells through generation of the release of cytokines and cytotoxicity. What is certain is that KIRs are genetically polymorphic and the extent of KIRs diversity within the individuals may have the potential outcomes for hematopoietic stem cell transplantation (HSCT). In this regard, recent studies suggest that KIR is as imperative as its ligand (HLA) in stem cell transplantation for malignant diseases. However, unlike HLA epitope mismatches, which are well-known causes of NK alloreactivity, a complete understanding of KIR genes' role in HSCT remains unclear. Because of genetic variability in KIR gene content, allelic polymorphism, and cell-surface expression among individuals, an appropriate selection of donors based on HLA and KIR profiles is crucial to improve outcomes of stem cell transplantation. In addition, the impact of the KIR/HLA interaction on HSCT outcomes needs to be investigated more comprehensively. The present work aimed to review the NK cell regeneration, KIR gene polymorphisms, and KIRligand binding on outcomes in hematologic malignancies following haploidentical stem cell transplantation. Comprehensive data gathered from the literature can provide new insight into the significance of KIR matching status in transplantations.
Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Ligantes , Antígenos HLA/genética , Recidiva Local de Neoplasia , Receptores KIR/genética , Receptores KIR/metabolismo , Polimorfismo Genético , Antígenos de Histocompatibilidade , Transplante de Células-Tronco , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapiaRESUMO
BACKGROUND: Hemorrhagic cystitis (HC) is an important adverse event experienced after hematopoietic stem cell transplantation (HSCT). Severe HC could lead to significant morbidity, prolonged hospitalization with increased health-care costs, and may cause considerable mortality. OBJECTIVES: In order to investigate the influence of different contributing factors other than BK viruria on HC occurrence in a homogenous population, we retrospectively analyzed the potential risk factors. STUDY DESIGN: We conducted a retrospective study among 200 patients (median age 12.4 years, IQR: 7.9-16.1) with acute leukemia who received peripheral blood allogenic HSCT after radiation-free myeloablative conditioning regimen, in pediatric cell therapy department of Research Institute for Oncology, Hematology and Cell Therapy (RIOHCT), Tehran, Iran, between December 2014 and December 2021. Associations between risk factors and outcomes were examined by univariable and multivariable logistic regression models. RESULTS: A total of 46 patients (23%) had developed HC during the study period. The median onset of HC was 29 (IQR: 24-37) days post-transplant, and it persisted for a median of 33 (7-270) days. The incidence of HC in our patients was estimated to be 3 in 1000 cases (95% CI: 2-4). The results of multivariable logistic model shows that the chance of HC in T-cell acute lymphoblastic leukemia (ALL) compared to B-cell All is nearly five times more (OR = 4.88; 95%CI: (1.51-15.78), P = 0.008). The incidence of HC in patients who underwent HSCT from haploidentical donors was significantly higher than full matched donors (P < 0.001). Undergoing transplant from a matched unrelated and haploidentical donor both augment the chance of HC in about six times more than matched related donors (OR = 6.36; 95%CI: (1.58-25.49), P = 0.009 and OR = 5.7; 95%CI: (1.83-17.75), P = 0.003, respectively). In patients who developed HC compared to non-HC group, overall survival was much worse (P < 0.001). DISCUSSION: Most studies have failed to demonstrate any relationship between late-onset HC and the dose of cyclophosphamide. In our study, although the dose of cyclophosphamide was similar in HSCT from MRD and MUD, the hazard of HC incidence was significantly higher in the latter group. This could be accredited to ATG, as in patients in the MRD group who had not received any ATG, the incidence of HC was much lower than the patients who had underwent HSCT from MUD or haploidentical donor group. CONCLUSIONS: Patients with T-cell ALL and those who under haploidentical HSCT had the highest incidence of HC.
Assuntos
Cistite , Leucemia , Transplante de Células-Tronco de Sangue Periférico , Criança , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Incidência , Irã (Geográfico) , Hemorragia , Fatores de Risco , Cistite/epidemiologia , Cistite/etiologia , Ciclofosfamida , Leucemia/terapia , Leucemia/complicações , Doença AgudaRESUMO
Acute lymphoblastic leukemia (ALL) is a malignancy of bone marrow lymphoid precursors. Despite effective treatments, the causes of its progression or recurrence are still unknown. Finding prognostic biomarkers is needed for early diagnosis and more effective treatment. This study was performed to identify long non-coding RNAs (lncRNAs) involved in ALL progression by constructing a competitive endogenous RNA (ceRNA) network. These lncRNAs may serve as potential new biomarkers in the development of ALL. The GSE67684 dataset identified changes in lncRNAs and mRNAs involved in ALL progression. Data from this study were re-analyzed, and probes related to lncRNAs were retrieved. Targetscan, miRTarBase, and miRcode databases were used to identify microRNAs (miRNAs) related to the discovered genes and lncRNAs. The ceRNA network was constructed, and the candidate lncRNAs were selected. Finally, the results were validated with reverse transcription quantitative real-time PCR (RT-qPCR). The ceRNA network outcomes demonstrated that the top lncRNAs associated with altered mRNAs in ALL are IRF1-AS1, MCM3AP-AS1, TRAF3IP2-AS1, HOTAIRM1, CRNDE, and TUG1. Investigations of the subnets linked to MCM3AP-AS1, TRAF3IP2-AS1, and IRF1-AS1 indicated that these lncRNAs were considerably related to pathways associated with inflammation, metastasis, and proliferation. Higher expression levels of IRF1-AS1, MCM3AP-AS1, TRAF3IP2-AS1, CRNDE, and TUG1 were found in ALL samples compared to controls. The expression of MCM3AP-AS1, TRAF3IP2-AS1, and IRF1-AS1 is significantly elevated during the progression of ALL, playing an oncogenic role. Due to their role in the main cancer pathways, lncRNAs could be suitable therapeutic and diagnostic targets in ALL.
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MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inflamação , Acetiltransferases , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Fanconi anemia (FA) is a rare and complex genetic disorder, clinically characterized by bone marrow failure, congenital defects, and cancer predisposition. Hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis after the occurrence of marrow failure or clonal hematopoietic abnormality. However, radiation exposure during transplant may increase the risk of later malignancies. In this retrospective study, we analyzed the results of HSCT with a radiation-free, busulfan-based conditioning regimen in FA patients. A total of 122 patients (median age: 8 years, range: 2-18 years) with FA who underwent HSCT between January 2008 and January 2020 were enrolled in this study and followed up to the end of 2020. The preparative regimen included busulfan (0.2 mg/kg/day, days -9 to -6), cyclophosphamide (15 mg/kg/day, days -5 to -2), and in vivo T-cell depletion with rabbit anti-thymocyte globulin. All patients received graft-versus-host disease prophylaxis with cyclosporine combined with methotrexate. We used the Kaplan-Meier method, log-rank test, and Cox proportional hazards models to analyze patient survival. Peripheral blood, bone marrow and cord blood hematopoietic stem cells were used in 84 (68.9%), 31 (25.4%) and 7 (5.7%) patients, respectively. Donors were matched siblings in 48 (39.3%), matched other relatives in 56 (45.9%), and matched unrelated persons in 18 (14.8%) patients. With a median follow-up time of 24.25 months, graft rejection occurred in only one patient. The 1- and 5-year overall survival rates were 84.14% (95% confidence interval: 76.02-89.70) and 82.16% (95% confidence interval: 73.01-88.45), respectively. Of the patient characteristics documented before transplant, the presence of cardiopulmonary, genitourinary tract, central nervous system, and limb malformations significantly affected survival rates. Our results indicate excellent outcomes in patients with FA undergoing HSCT with a radiation-free, busulfan-based conditioning regimen. It would be desirable to aim at optimizing the outcome of HSCT in FA patients in future studies.
Assuntos
Anemia de Fanconi , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano/uso terapêutico , Anemia de Fanconi/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Prognóstico , Estudos Retrospectivos , Linfócitos T , Condicionamento Pré-Transplante/métodos , Doadores não RelacionadosRESUMO
BACKGROUND AND AIMS: Acinetobacter baumannii is among the most concerning cause of nosocomial infections due to its high level of antibiotic resistance and high mortality. The aim of this study was to determine the role of efflux pumps in resistance of A. baumannii strains to three disinfectants, including MICROZED ID-MAX, NANOSIL D2, and OPIDEX OPA. METHODS: Twenty-eight environmental and clinical isolates of A. baumannii were collected from selected hospitals of central Iran. The minimum inhibitory concentrations of the disinfectants were determined and real time reverse transcriptase-PCR was performed to investigate the expression level of qacEΔ1, amvA, abeM, and adeB efflux pump genes. RESULTS: Considering both clinical and environmental isolates, there was a significant difference in the mean expression level of qacEΔ1 gene between susceptible and resistant strains to MICROZED ID-MAX disinfectant, of amvA and abeM genes between susceptible and resistant strains to NANOSIL D2 disinfectant and of abeM gene in susceptible and resistant strains to OPIDEX OPA disinfectant (all P Ë .05). The expression levels of abeM and amvA genes were higher in the environmental isolates that were resistant to NANOSIL D2 disinfectant compared to those that were susceptible (P Ë .05). CONCLUSIONS: This study provided evidence for the role of abeM and amvA genes in the resistance of environmental isolates to disinfectants, particularly hydrogen peroxide derivatives.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) potentially renders thalassemia patients disease-free with presumably cessation of associated complications. This study analyzes the liver fibrosis status and the determinants of its progression in ex-thalassemic patients. The liver fibrosis status of 108 pediatric transfusion-dependent ß-thalassemia major patients was evaluated before and one year after allo-HSCT using transient elastography (TE). All patients achieved normal hematopoiesis. In univariate analyses, not in all, but in patients developing significant post-HSCT iron overload or hepatic graft-versus-host disease (GvHD), as well as recipients of bone marrow stem cells (BMSC), significant TE increment occurred. In multivariable analyses, through a model with large effect size (Adj.R2 = 26%, F(3,104) = 13.53, P < 0.001), post-HSCT serum ferritin and hepatic GvHD were ascertained as independent determinants of significant TE increase, and the effect of stem cell graft source approached the level of significance. Excluding the patients with intermediate/high Lucarelli risk classes, the TE increase was significantly greater only in BMSC recipients (P = 0.033). Although the risk impact of allograft source on liver fibrosis progression requires further evaluation; hepatic status of ex-thalassemic patients can be preserved after HSCT, if hepatic GvHD is controlled and adequate post-transplantation iron depletion is ensured.
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Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Cirrose Hepática/etiologia , Talassemia beta/complicações , Talassemia beta/terapia , Adolescente , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Técnicas de Imagem por Elasticidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Cirrose Hepática/diagnóstico , Masculino , Estudos Prospectivos , Transplante HomólogoRESUMO
BACKGROUND: Hepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major. METHODS: Between April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time. RESULTS: The 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs. CONCLUSIONS: Based on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Talassemia beta , Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas , Humanos , Irã (Geográfico) , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/terapia , Talassemia beta/terapiaRESUMO
BACKGROUND: Cancer patients, with an incidence of more than 18 million new cases per year, may constitute a significant portion of the COVID-19 infected population. In the pandemic situation, these patients are considered highly vulnerable to infectious complications due to their immunocompromised state. MATERIAL & METHODS: In this retrospective case series, the documents of solid cancer patients infected by SARS-CoV-2, hospitalized in Shariati hospital between 20 February and 20 April 2020, were evaluated. The diagnosis of COVID-19 was based on laboratory-confirmed COVID-19 and/or features of chest CT scan highly suggestive for SARS-CoV-2. RESULTS: A total of 33 COVID-19-infected cancer patients were included. Mean age was 63.9 years, and 54.5% of the patients were male. LDH level was significantly higher (1487.5 ± 1392.8 vs. 932.3 ± 324.7 U/L, P-value=0.016) and also serum albumin was significantly lower in non-survivors (3.6 ± 0.5 vs. 2.9 ± 0.6 g/dL, p-value=0.03). Among 16 patients with stage IV cancer, thirteen patients died, which was significantly higher compared to stage I-III cancer patients (81.3% vs. 18.8% P-value= <0.001). In terms of developing complications, sepsis, invasive ventilation and mortality was significantly higher in patients who received cytotoxic chemotherapy within the last 14 days. CONCLUSION: In this study, we showed that the mortality rate among cancer patients affected by COVID-19 was higher than general population and this rate has a significant correlation with factors including the stage of the disease, the type of cancer, the activity of cancer and finally receiving cytotoxic chemotherapy within 14 days before diagnosis of COVID-19.
Assuntos
COVID-19/prevenção & controle , Hospitalização/estatística & dados numéricos , Neoplasias/terapia , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Pandemias , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Taxa de SobrevidaRESUMO
Allogeneic hematopoietic stem-cell transplantation is a well-known curative treatment for patients with chronic granulomatous disease. We present our experiment regarding ten patients with chronic granulomatous disease who underwent a reduced intensity conditioning regimen consisting of melfalan, fludarabine, and antithymocyte globulin. Donor lymphocyte infusion was used in three representative patients who developed mixed donor chimerism. After at least 2 years of median follow-up, 8 of the 10 patients are alive and well.
RESUMO
Background: The first cases of proved COVID-19 in Iran were reported in February 2020 and has since rapidly spread worldwide. We aimed to clarify the clinical significance of hematologic parameters alteration in COVID-19. Methods: Different hematologic parameters were measured in 225 hospitalized COVID-19 patients in a tertiary care university hospital, during the peak of COVID-19 outbreak and their association with duration of hospitalization, ICU admission and especially mortality was analyzed. Results: Among a total of 225 patients, 24.4% did not survive after admission. Lymphopenia and neutrophilia were observed in 52.7% and 21.4% of the patients, respectively. The mean count of neutrophils was significantly higher in non-survived patients (P = .032). Elevated neutrophil-to-lymphocyte ratio (NLR) was significantly associated with mortality (P < .001). Low hemoglobin (Hb) concentration significantly correlated with mortality (P = .004) and ICU admission (P = .04). Platelet (Plt) count was significantly lower in the non-survived patients (P = .023). Non-survivors had significantly lower nadir Hb and Plt counts than survivors (P < .001 in both parameters). Platelet-to-lymphocyte ratio (PLR) also correlated with mortality and was significantly higher in non-survivors (P = .034). Conclusions: Hematologic laboratory parameters have always been a crucial component of diagnostic and therapeutic strategies in infectious disease. Hematologic predictors of a fatal outcome in COVID19 hospitalized patients in our series include elevated NLR and PLR, lower than normal Hb and Plt, elevated d-dimer and prolonged prothrombin time (PT), together with elevated inflammatory indicators in the blood.
Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Mortalidade Hospitalar , Pandemias , Pneumonia Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Contagem de Células Sanguíneas , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19 , Infecções por Coronavirus/mortalidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoglobinas/análise , Hospitais Universitários , Humanos , Inflamação , Pacientes Internados/estatística & dados numéricos , Irã (Geográfico)/epidemiologia , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Pró-Calcitonina/sangue , Estudos Retrospectivos , SARS-CoV-2 , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for thalassemia major (TM). Infertility and its indicators have been assessed in transfusion dependent TM men, but in this study, we sought to compare the fertility indicators of TM patients after HSCT with those in patients treated conventionally. The possible influential factors on reproductive capacity in TM patients undergone allogeneic HSCT were also evaluated. PATIENTS AND METHODS: In this cross-sectional study, we compared the gonadal hormones level, testicular volume, Tanner stage and sperm analysis in transfusion-dependent thalassemia major (TDTM) patients who survived matched sibling HSCT (n = 43) with patients conventionally treated by transfusion and iron chelation (n = 52). RESULTS: The patients' age range was between 16 to 41 years. Tanner stage 4-5 was seen in 39 patients (41%). The prevalence of hypogonadism in our patients was 32.63% but its frequency was not significantly different between the two groups (p = 0.35). Azospermia, oligospermia, astenospermia, teratospermia and even having dry and low volume ejaculate were all significantly more frequent in the post-transplant patients compared to TDTM group. In the post-HSCT group, neither patients' age at transplantation nor the conditioning regimen used in their transplant process did significantly affect their hormonal status and sperm parameters. Chronic graft versus host disease (GVHD) occurred in 14 (40%) patients. No significant difference was observed between the grade of chronic GVHD and hypogonadism (P = 0.853). CONCLUSIONS: Thalassemia patients undergone allogeneic HSCT have lower fertility potential, mainly in sperm parameters compared with patients treated with blood transfusion and chelation. This information is important for thalassemic patients considering HSCT.