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1.
Ann Hematol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758360

RESUMO

The combination of cladribine, cytarabine, and G-CSF (CLAG) has exhibited robust synergistic anti-leukemia activity as an induction therapy (IT) in acute myeloid leukemia (AML). However, the impact of CLAG as a bridging therapy (BT) administered between IT and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with relapsed or refractory (R/R) AML remains uncertain. In this retrospective study, we examined the efficacy of CLAG as a transitional strategy prior to allo-HSCT in R/R AML. We included 234 patients with R/R AML who received the modified busulfan plus cyclophosphamide conditioning regimen for allo-HSCT in our center during the past 6 years, performed a propensity-score matching analysis, partitioned them into four distinct cohorts, and further integrated them into the CLAG group and non-CLAG group based on response to IT and utilization of CLAG. Our cohorts encompassed 12 patients in Cohort A (modified composite complete remission (mCRc) after IT, CLAG), 31 in Cohort B (mCRc after IT, non-CLAG), 35 in Cohort C (non-complete remission (non-CR) after IT, CLAG), and 80 in Cohort D (non-CR after IT, non-CLAG). Intriguingly, among patients with non-CR status, the administration of CLAG correlated with a notably statistically diminished risk of relapse and improved survival at 2-year follow-up (Cohort C vs. Cohort D). Employing CLAG as a BT prior to allo-HSCT demonstrates substantial effectiveness, a relative degree of safety, and manageable toxicity in selected R/R AML cases.

2.
Cell Transplant ; 33: 9636897241254678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798038

RESUMO

Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.


Assuntos
Doença Enxerto-Hospedeiro , Janus Quinase 1 , Prednisona , Humanos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Prednisona/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/metabolismo , Doença Crônica , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Idoso , Quimioterapia Combinada , Síndrome de Bronquiolite Obliterante
3.
Transplant Cell Ther ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740139

RESUMO

The objective is to underscore the significance of pre-existing anti-HLA Abs in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for SAA. A retrospective analysis was conducted using data from 244 SAA patients who underwent allo-HSCT between January 2016 and October 2022. The patient cohort was divided into 2 groups based on the presence of pre-existing anti-HLA Abs. Out of 244 SAA patients, 82 were tested positive for anti-HLA Abs. Seventeen patients were tested with DSA in haplo-HSCT. We found that the presence of pre-existing anti-HLA Abs did not influence neutrophil engraftment (P = .600); however, it resulted in delayed platelet recovery (P = .006). Comparatively, patients with anti-HLA Abs demonstrated lower overall survival (OS) compared to their counter parts without anti-HLA Abs (P = .001), with a correspondingly elevated transplant-related mortality (TRM) in the former group (P = .002). Multivariate analysis established pre-existing anti-HLA Abs as an independent risk factor for impaired platelet recovery (HR 1.67, 95% CI 1.16 to 2.44, P = .006) and OS (HR 2.19, 95% CI 1.03 to 4.67, P = .043). However, there were no differences between DSA and non-DSA patients after desensitization in haplo-HSCT. In summary, the presence of pre-existing anti-HLA Abs in SAA patients undergoing allo-HSCT appears to detrimentally affect platelet recovery and overall prognosis.

4.
Chem Sci ; 15(15): 5730-5737, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638226

RESUMO

Aspidosperma and uleine alkaloids belong to the large family of monoterpene indole alkaloids with diverse biological activities and thus have attracted extensive synthetic interest. Reported is the development of a new synthetic strategy that allows direct C3-C2' linkage of indoles with functionalized 2-hydroxypiperidines to construct the core common to all aspidoserma and uleine alkaloids. Such indole-piperidine linkage is enabled by coupling aza-Achmatowicz rearrangement (AAR) with indoles via an intermolecular aza-Friedel-Crafts (iAFC) reaction. This AAR-iAFC reaction proceeds under mild acidic conditions with wide tolerance of functional groups (33 examples). The synthetic application of the AAR-iAFC method was demonstrated with collective total syntheses of 3 uleine-type and 6 aspidosperma alkaloids: (+)-3-epi-N-nor-dasycarpidone, (+)-3-epi-dasycarpidone, (+)-3-epi-uleine, 1,2-didehydropseudoaspidospermidine, 1,2-dehydroaspidospermidine, vincadifformine, winchinine B, aspidospermidine, and N-acetylaspidospermidine. We expect that this AAR-iAFC strategy is applicable to other monoterpene indole alkaloids with the C3-C2' linkage of indoles and piperidines.

5.
J Stroke Cerebrovasc Dis ; 33(6): 107682, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522758

RESUMO

OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.


Assuntos
Transtornos de Deglutição , Deglutição , Acidente Vascular Cerebral , Gravação em Vídeo , Humanos , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/diagnóstico por imagem , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Fluoroscopia , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Fatores de Tempo , Fatores de Risco , Estudos Retrospectivos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38461040

RESUMO

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

7.
Leuk Lymphoma ; : 1-9, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475670

RESUMO

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.

8.
J Cell Mol Med ; 28(3): e18114, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38323741

RESUMO

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).


Assuntos
Proteínas de Fusão Oncogênica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Proteína 2 de Ligação a Repetições Teloméricas , Animais , Humanos , Camundongos , Carcinogênese , Transformação Celular Neoplásica , Mesilato de Imatinib , Inibidores de Proteínas Quinases/farmacologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Transdução de Sinais , Fator de Transcrição STAT5/genética , Proteína 2 de Ligação a Repetições Teloméricas/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
10.
Stem Cell Res Ther ; 15(1): 24, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38282037

RESUMO

BACKGROUND: Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe. METHODS: Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests. RESULTS: The median age of the cohort was 57 years (range: 55-75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043). CONCLUSION: The choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Idoso , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante , China , Síndromes Mielodisplásicas/terapia
11.
Diabetes Metab Syndr Obes ; 17: 417-426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38288341

RESUMO

Purpose: To investigate the risk factors associated with subclinical diabetic peripheral neuropathy (sDPN) in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This cross-sectional, retrospective study involved 311 patients with T2DM who were successively admitted from January 2018 to December 2021 without any neurological symptoms. All participants underwent a nerve conduction study (NCS), and those asymptomatic patients with abnormal nerve conduction were diagnosed with sDPN. Differences between groups were evaluated by the chi-squared, Wilcoxon, or Fisher's exact test. Binary logistic regression analysis was performed to determine the independent risk factors for sDPN. Receiver operating characteristic (ROC) curves were constructed, and the areas under curves (AUCs) were detected. Results: Among 311 asymptomatic patients with T2DM, 142 (45.7%) with abnormal nerve conduction were diagnosed with sDPN. Patients with sDPN significantly differed from those without diabetic peripheral neuropathy (DPN) in age, history of hypertension, duration of diabetes, anemia, neutrophil-to-lymphocyte ratio, fasting C-peptide level, serum creatinine level, and albuminuria (all p<0.05). Furthermore, the duration of diabetes (odds ratio [OR]: 1.062, 95% confidence interval [CI]: 1.016-1.110), fasting C-peptide level (OR: 2.427, 95% CI: 1.126-5.231), and presence of albuminuria (OR: 2.481, 95% CI: 1.406-4.380) were independently associated with the development of sDPN (all p<0.05). The AUCs for fasting C-peptide level, duration of diabetes, and the two factors combined were 0.6229 (95% CI: 0.5603-0.6855, p=0.0002), 0.6738 (95% CI: 0.6142-0.7333, p<0.0001), and 0.6808 (95% CI: 0.6212-0.7404, p<0.0001), respectively. Conclusion: For patients with T2DM and longer duration of diabetes, lower fasting C-peptide levels, and presence with albuminuria, the risk for developing DPN is higher even if they have no clinical signs or symptoms. Identifying potential risk factors for the development of sDPN and effectively controlling them early are critical for the successful management of DPN.

13.
Ther Apher Dial ; 28(1): 141-151, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37461148

RESUMO

INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases , Encefalite , Humanos , Proteínas do Tecido Nervoso , Encefalite/terapia , Anticorpos , Corticosteroides , Plasmaferese , Autoanticorpos
14.
HLA ; 103(1): e15286, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38018476

RESUMO

Few studies have performed comparative analysis of the outcome of hematopoietic stem cell transplantation from HLA-identical sibling donors (ISD-HSCT) in patients with or without anti-HLA Abs. In this study we retrospectively collected data from a multicenter study to analyze the distribution and impact of the pre-existing anti-HLA Abs in ISD-HSCT. Among 402 recipients, 111 were positive for anti-HLA Abs. Gender, time from diagnosis to transplantation and distribution of primary disease might be risk factors for the occurrence of anti-HLA Abs. We found that patients with anti-HLA Abs had delayed neutrophil engraftment and were more vulnerable to experience Cytomegalovirus (CMV) reactivation. The presence of anti-HLA Abs was proved to be an independent risk factor for neutrophil engraftment (HR 1.42 95% CI 1.13-1.80, p = 0.003) and CMV reactivation (HR 2.03 95% CI 1.19-3.46, p = 0.009). We found that anti-HLA Abs have a negative impact on the prognosis in the early period after transplantation from sibling donors and anti-HLA Abs was also an independent risk factor for the overall survival (OS) at 180 days (HR 2.32, 95% CI 1.03-5.27, p = 0.042) among female recipients. In conclusion, anti-HLA Abs have a negative impact on the prognosis early after ISD-HSCT.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Feminino , Estudos Retrospectivos , Irmãos , Alelos , Doadores de Tecidos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
15.
Front Oncol ; 13: 1302356, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38098504

RESUMO

Background: Satisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence. Methods: Here, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes. Results: According to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model's risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines. Conclusions: The 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.

16.
J Fluoresc ; 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157082

RESUMO

In this work, bright yellow fluorescent and multifunctional carbon dots (N-CDs) were prepared by hydrothermal method from O-phenylenediamine and 4-aminobenzoic acid. The fluorescence characterization showed that the N-CDs possessed good optical properties (QY = 32%) and excitation dependent multi-color emission. By exciting with 390 nm, the strong selective interaction of VB12 with N-CDs could result in a sharp decrease in the luminescence of N-CDs at 567 nm. An efficient fluorescence sensor in aqueous solution was constructed which could linearly respond VB12 in wide concentration ranges of 0-90 µM and 140-250 µM. The linear correlation coefficients of N-CDs and VB12 were 0.9950 and 0.9968, respectively, and the detection limit was 0.119 µM. N-CDs were performed for sensitive determination of VB12 in real samples. Moreover, the N-CDs were exploited to image cell. This N-CDs was a sensitive fluorescence probe to monitor VB12 and presented prospective potential in living cells imaging. Schematic diagram of the synthesis process and application research of N-CDs.

17.
EJHaem ; 4(4): 1208-1211, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024627

RESUMO

Adverse-risk acute myeloid leukemia (AML) has a dismal prognosis. We aimed to investigate the activity and tolerability of venetoclax combined with homoharringtonine (HHT) plus cytarabine (VHA) regimen for de novo adverse-risk AML. Thirteen de novo AML patients with adverse-risk factors were treated with venetoclax (100 mg day 1, 200 mg day 2, 400 mg days 3-21), HHT (1 mg/m2 days 1-5) and cytarabine (100 mg/m2 days 1-5) (VHA regimen). Complete remission (CR) was achieved in 11/13 patient (84.6%), all of CR responders were measurable residual disease (MRD) negative detected by multi-parameter flow cytometry (MFC). Grade 3-4 neutropenia, anaemia, and thrombocytopenia occurred in most patients. Grade 3-4 non haematological adverse events (AEs) included febrile neutropenia (4/13, 30.8%). With a median follow-up of 10 months (range 4-19), median overall survival and event-free survival were not reached. VHA may be a promising and well-tolerated regimen in de novo adverse-risk AML.

18.
Front Immunol ; 14: 1252879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954615

RESUMO

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Humanos , Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Seguimentos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Infecções por Vírus Epstein-Barr/complicações , Células-Tronco de Sangue Periférico/patologia , Herpesvirus Humano 4 , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/patologia , Neoplasias/tratamento farmacológico
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