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The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.
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The anodeless battery design has recently gained significant interest by eliminating the direct use of a thick lithium (Li) foil. However, it suffers from inhomogeneous Li+ flux, resulting in dendrite growth and a short cycling life. To address this, the exfoliation of layered-structure titanium oxide to 2D nanosheets (2DTiOx) is proposed to precisely control Li+ flux at the atomic scale by maximizing Li+ affinitive Ti sites. Compared to cells without these nanosheets, the Li|2DTiOx|Cu half-cell demonstrates stable cyclability over 900 cycles, with a Coulombic efficiency (CE) over 99% at 0.5 mA cm-2 and 0.5 mAh cm-2. Similarly, a long stable cycling life over 1500 h at 1.0-3.0 mA cm-2 is observed for a 2DTiOx-based symmetric cell containing a limited Li amount from electrodeposited Li metal (e-Li|2DTiOx|e-Li). The full cells (e-Li|2DTiOx||NCM811 and e-Li|2DTiOx||LFP) coupled with NCM811 and LFP cathodes showed a long cycle life of 400 cycles at 1.0 C and 0.5 C, respectively. The exceptional battery performance is attributed to the uniform Li disposition on the 2DTiOx electrode, emphasizing the crucial role of the exposed basal plane in 2DTiOx as an efficient atomic scale Li+ flux regulator. This strategy is expected to advance next-generation lithium metal batteries (LMBs) by highlighting the significance of Li+ affinity at the Ti sites of 2DTiOx nanosheets.
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Photomultiplication (PM)-type organic photodetectors (OPDs), which typically form a homogeneous distribution (HD) of n-type dopants in a p-type polymer host (HD PM-type OPDs), have achieved a breakthrough in device responsivity by surpassing a theoretical limit of external quantum efficiency (EQE). However, they face limitations in higher dark current and slower dynamic characteristics compared to p-n heterojunction (p-n HJ) OPDs due to inherent long lifetime of trapped electrons. To overcome this, a new PM-type OPD is developed that demonstrates ultrafast dynamic properties through a vertical phase separation (VPS) strategy between the p-type polymer and n-type acceptor, referred to as VPS PM-type OPDs. Notably, VPS PM-type OPDs show three orders of magnitude increase in -3 dB cut-off frequency (120 kHz) and over a 200-fold faster response time (rising time = 4.8 µs, falling time = 8.3 µs) compared to HD PM-type OPDs, while maintaining high EQE of 1121% and specific detectivity of 2.53 × 1013 Jones at -10 V. The VPS PM-type OPD represents a groundbreaking advancement by demonstrating the coexistence of p-n HJ and PM modes within a single photoactive layer for the first time. This innovative approach holds the potential to enhance both static and dynamic properties of OPDs.
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This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Perfil Genético , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Medição de RiscoRESUMO
Noise-vocoded speech has long been used to investigate how acoustic cues affect speech understanding. Studies indicate that reducing the number of spectral channel bands diminishes speech intelligibility. Despite previous studies examining the channel band effect using earlier event-related potential (ERP) components, such as P1, N1, and P2, a clear consensus or understanding remains elusive. Given our hypothesis that spectral degradation affects higher-order processing of speech understanding beyond mere perception, we aimed to objectively measure differences in higher-order abilities to discriminate or interpret meaning. Using an oddball paradigm with speech stimuli, we examined how neural signals correlate with the evaluation of speech stimuli based on the number of channel bands measuring N2 and P3b components. In 20 young participants with normal hearing, we measured speech intelligibility and N2 and P3b responses using a one-syllable task paradigm with animal and non-animal stimuli across four vocoder conditions with 4, 8, 16, or 32 channel bands. Behavioral data from word repetition clearly affected the number of channel bands, and all pairs were significantly different (p < 0.001). We also observed significant effects of the number of channels on the peak amplitude [F(2.006, 38.117) = 9.077, p < 0.001] and peak latency [F(3, 57) = 26.642, p < 0.001] of the N2 component. Similarly, the P3b component showed significant main effects of the number of channel bands on the peak amplitude [F(2.231, 42.391) = 13.045, p < 0.001] and peak latency [F(3, 57) = 2.968, p = 0.039]. In summary, our findings provide compelling evidence that spectral channel bands profoundly influence cortical speech processing, as reflected in the N2 and P3b components, a higher-order cognitive process. We conclude that spectrally degraded one-syllable speech primarily affects cortical responses during semantic integration.
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PURPOSE: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. MATERIALS AND METHODS: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. RESULTS: The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. CONCLUSION: AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Transplante Homólogo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Sistema de Registros , Taxa de SobrevidaRESUMO
Educating primary care physicians about blood donation and transfusion is critical. The Division of Hematology and Oncology at Soonchunhyang University Seoul Hospital in Korea introduced an on-site educational program termed the Blood Donation Center Visiting Program in the clerkship education for final-year medical students. We evaluated the educational outcomes and changes in perception among medical students after the Blood Donation Center Visiting Program based on a survey. The program was implemented from 2021 to 2023. As part of the program, students visited a blood donation center each week, one group at a time. They gained practical knowledge about the blood donation process, and some students actively participated in blood donation. After the program, 287 students were eligible for an online survey of the program, of whom 203 participated in the survey. Among the 203 students, 126 (62.1%) donated blood during their visit to the blood donation center as part of the program, and 88.7% of the students reported an increase (from 71.4% to 90.1%) in their knowledge and willingness to donate blood. The on-site educational Blood Donation Center Visiting Program appears to have generated positive changes in perceptions among students and enhanced their knowledge about blood donation.
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Doadores de Sangue , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Doadores de Sangue/psicologia , Conhecimentos, Atitudes e Prática em Saúde , República da Coreia , Percepção , Feminino , Masculino , Adulto Jovem , Doação de SangueRESUMO
INTRODUCTION: The role of inflammation in the pathophysiology of polycythemia vera (PV) is important. The presence of JAK2 mutations is important in the diagnosis of PV, and serum levels of erythropoietin (EPO) also play a supporting role. However, serum EPO levels show some limitations. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are a readily available marker of inflammation. Thus, we examined whether NLR & PLR might diagnose PV in erythrocytosis patients. We compared NLR & PLR and EPO diagnostic values. METHODS: We retrospectively reviewed clinical and laboratory data from two referral hospitals. Two hundred and eighty-five patients with erythrocytosis who underwent a test for the JAK2 mutation were included. It wac classified as the PV group and the secondary polycythemia (SP) group. RESULTS: The median NLR & PLR in the PV group (n = 70) was significantly higher than that in the SP group (n = 170) (NLR: 6.04 vs. 1.77, PLR: 283.18 vs. 101.56, respectively, p < 0.001). In the receiver operating characteristic analysis, the area under the curve of NLR & PLR was significantly higher than that of serum EPO (NLR vs EPO: 0.921 vs. 0.827, p = 0.003; PLR vs EPO: 0.917 vs 0.827, p = 0.003). CONCLUSION: In conclusion, NLR & PLR were higher in PV than in SP and showed better diagnostic value than serum EPO level, highlighting their potential as minor diagnostic criteria in patients with PV.
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Policitemia Vera , Policitemia , Humanos , Policitemia Vera/diagnóstico , Neutrófilos , Policitemia/diagnóstico , Estudos Retrospectivos , Plaquetas , Linfócitos , Inflamação , PrognósticoRESUMO
This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.
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Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T , Humanos , Estudos Retrospectivos , Transplante Homólogo , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento , Intervalo Livre de DoençaRESUMO
Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells; these include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPNs are inflammatory cancers, wherein the malignant clone generates cytokines that sustain the inflammatory drive in a self-perpetuating vicious cycle. The course of MPNs follows a biological continuum, that is, from early cancer stages (ET/PV) to advanced myelofibrosis as well as impending leukemic transformation. MPN-related symptoms, e.g., fatigue, general weakness, and itching, are caused by inflammatory cytokines. Thrombosis and bleeding are also exacerbated by inflammatory cytokines in patients with MPN. Until recently, the primary objective of ET and PV therapy was to increase survival rates by preventing thrombosis. However, several medications have recently demonstrated the ability to modify the course of the disease; symptom relief is expected for most patients. In addition, there is increasing interest in the active treatment of patients at low risk with PV and ET. This review focuses on the ET/PV treatment strategies as well as novel treatment options for clinical development.
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AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.
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Linfoma Folicular , Linfoma de Célula do Manto , Humanos , Adulto , Rituximab/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/radioterapia , Linfoma de Célula do Manto/etiologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/radioterapia , Radioimunoterapia/efeitos adversos , Radioimunoterapia/métodos , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.
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Anemia Ferropriva , Microbioma Gastrointestinal , Deficiências de Ferro , Microbiota , Humanos , Feminino , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico , Ferro/uso terapêuticoRESUMO
PURPOSE: We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. Materials and Methods: Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. RESULTS: Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). CONCLUSION: Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.
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Proteína alfa Estimuladora de Ligação a CCAAT , Leucemia Mieloide Aguda , Humanos , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Relevância Clínica , Intervalo Livre de Doença , Nucleofosmina , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Prognóstico , Cariótipo , Proteínas Estimuladoras de Ligação a CCAAT/genéticaRESUMO
PURPOSE: The purpose of this study is to share our outcomes and experiences on allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients aged 60 years and older with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in South Korea, and to compare them with other studies. MATERIALS AND METHODS: We analyzed the clinical outcomes of 116 patients with AML or MDS aged 60 years and older who underwent allogeneic HSCT. We also analyzed which pretreatment factors affect the overall survival (OS) after allogeneic HSCT. RESULTS: Neutrophil and platelet engraftment were achieved at median day +11 [interquartile range (IQR) 10-15] and +14 (IQR 11-19), respectively. A complete donor chimerism was confirmed in 65 (56.0%) patients at 3 weeks and in 63 (54.3%) patients at 3 months after HSCT. The estimated incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 was 13.7%. The estimated incidence of chronic GVHD at 2 years was 38.8%. Within a median follow-up of 14 months after HSCT, OS was 64% at 1 year and 55% at 2 years, and non-relapse mortality (NRM) was 20% at 1 year and 28% at 2 years. Multivariate analysis revealed that male sex and Hematopoietic Cell Transplantation-Specific Comorbidity Index ≥3 were associated with poor OS. CONCLUSION: This study showed that allogeneic HSCT in elderly adults aged 60 and older can be performed with successful engraftment and acceptable NRM and OS are expected given the generally known survival of patients with higher risk MDS and poor risk AML.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Recidiva , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-TransplanteRESUMO
Lithium (Li) is the "holy grail" for satisfying the increasing energy demand. This is because of its high theoretical capacity and low potential. Although Li is considered as a potential anode material, dendritic Li growth and the limited electrochemical properties continue to hinder its practical application. Structure-based self lithium ion (Li+ ) concentrating electrodes with high capacity and uniform Li+ -flux are recommended to overcome these shortcomings of Li. However, recent studies have been limited to structural perspectives. In addition, the electrokinetic principle of electrode materials remains a challenge. Herein, the space-confinement-based strategy is suggested for condensed Li+ -flux control in nanoscaled slit spaces that induce the dense Li growth on an anodeless electrode by using the stratified carbon pack (SCP). The micro/mesoporous slits of the SCP concentrate the electric field, which is strengthened by the space-confined electric field focusing, resulting in the accumulation of Li+ -flux in the host. The accumulated Li+ in host sites enables a uniform Li deposition with high capacity at high current density stably. Furthermore, SCPs have great compatibility with LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathode, representing the outstanding full cell performance with Li deposited electrode which show the high specific of 115 mAh g-1 at 4 C during 350 cycles.
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PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. MATERIALS AND METHODS: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. RESULTS: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). CONCLUSION: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Rituximab/uso terapêutico , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante Autólogo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , República da CoreiaRESUMO
PURPOSE: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin's lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. MATERIALS AND METHODS: Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days -7, -6, and -5, etoposide (400 mg/m2 intravenously) on days -5 and -4, and melphalan (50 mg/m2/day intravenously) on days -3 and -2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days -7, -6, and -5, etoposide (400 mg/m2/day intravenously) on days -5 and -4, and cyclophosphamide (50 mg/kg/day intravenously) on days -3 and -2. The primary endpoint was 2-year progression-free survival (PFS). RESULTS: Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. CONCLUSION: There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.
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Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Linfoma , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Etoposídeo , Bussulfano/efeitos adversos , Melfalan/efeitos adversos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/etiologia , Ciclofosfamida , Terapia ComportamentalRESUMO
Secondary-type mutations (STMs), namely SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, and STAG2, are more frequently detected in secondary acute myeloid leukemia (AML) than in de novo AML. Whether de novo AML with STMs should be differently managed is, however, unclear. In 394 patients diagnosed with de novo AML who had a normal karyotype, the genetic profiling via targeted deep sequencing of 45 genes revealed 59 patients carrying STMs (STM+). The STM+ group showed shorter overall survival (OS) than the STM- group (5-year OS, 15.3 vs. 31.0%) (hazard ratio [HR]: 1.975, 95% confidence interval [CI]: 1.446-2.699, p < 0.001). Among the 40 STM+ patients who achieved CR, those who received allogeneic HCT (n = 15) showed better OS (5-year OS, 40.0 vs. 12.0%) (HR: 0.423, 95% CI: 0.184-0.975, p = 0.043) and relapse-free survival (5-year, 40.0 vs. 8.0%) (HR: 0.438, 95% CI: 0.189-1.015, p = 0.054) than those who received consolidation chemotherapy only. The cumulative incidence of relapse was lower in the patients who received allogeneic HCT (5-year, 33.3 vs. 60.0%) (HR: 0.288, 95% CI: 0.111-0.746, p = 0.011), and non-relapse mortality was similar between the two groups (p = 0.935). In conclusion, STM is an independent prognostic factor for adverse outcomes in AML that can be overcome by allogeneic HCT.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Intervalo Livre de Doença , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Mutação , RecidivaRESUMO
Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for ß-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The ß-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072â1.5726). Conclusion: The detection rate of GD in probable high-risk patients in Korea was lower than expected. However, the role of hemato-oncologists is still important in the diagnosis of GD.