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Tumor-derived factors are thought to regulate thrombocytosis and erythrocytopenia in individuals with cancer; however, such factors have not yet been identified. Here we show that tumor cell-released kynurenine (Kyn) biases megakaryocytic-erythroid progenitor cell (MEP) differentiation into megakaryocytes in individuals with cancer by activating the aryl hydrocarbon receptor-Runt-related transcription factor 1 (AhR-RUNX1) axis. During tumor growth, large amounts of Kyn from tumor cells are released into the periphery, where they are taken up by MEPs via the transporter SLC7A8. In the cytosol, Kyn binds to and activates AhR, leading to its translocation into the nucleus where AhR transactivates RUNX1, thus regulating MEP differentiation into megakaryocytes. In addition, activated AhR upregulates SLC7A8 in MEPs to induce positive feedback. Importantly, Kyn-AhR-RUNX1-regulated MEP differentiation was demonstrated in both humanized mice and individuals with cancer, providing potential strategies for the prevention of thrombocytosis and erythrocytopenia.
Assuntos
Neoplasias , Trombocitose , Animais , Camundongos , Cinurenina/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Megacariócitos/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Células Precursoras Eritroides/metabolismo , Diferenciação Celular/fisiologia , Neoplasias/metabolismo , Trombocitose/metabolismo , ViésRESUMO
The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.
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The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.
Assuntos
Antineoplásicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Tretinoína/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab/administração & dosagem , Prevenção Secundária , Tretinoína/administração & dosagemRESUMO
The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19.
Assuntos
COVID-19 , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , Estudos Prospectivos , Contagem de Plaquetas , PlaquetasRESUMO
Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
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Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.
Assuntos
Hemorragia Pós-Parto/etiologia , Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Idiopática/complicações , Adulto , Área Sob a Curva , China/epidemiologia , Estudos de Coortes , Suscetibilidade a Doenças , Registros Eletrônicos de Saúde , Feminino , Seguimentos , Previsões , Geografia Médica , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Recém-Nascido , Modelos Logísticos , Modelos Teóricos , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Prednisona/uso terapêutico , Gravidez , Resultado da Gravidez , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.
Assuntos
Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do TratamentoRESUMO
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.
Assuntos
Creatinina/sangue , Bases de Dados Factuais , Hemoglobinas/metabolismo , Modelos Biológicos , Púrpura Trombocitopênica Trombótica/sangue , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (Pâ¯=â¯.043) and cytomegalovirus (CMV) viremia (Pâ¯=â¯.035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (Pâ¯=â¯.619), disease-free survival (Pâ¯=â¯.609), nonrelapse mortality (Pâ¯=â¯.87), or the incidence of relapse (Pâ¯=â¯.583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (Pâ¯=â¯.012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.
Assuntos
Doença Enxerto-Hospedeiro , Síndrome de Guillain-Barré , Transplante de Células-Tronco Hematopoéticas , Fatores Imunológicos/administração & dosagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Tiamina/administração & dosagem , Vitamina B 12/administração & dosagem , Adolescente , Adulto , Aloenxertos , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/mortalidade , Humanos , Incidência , Masculino , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/mortalidade , Fatores de Risco , Taxa de SobrevidaRESUMO
Hepatic sinusoidal obstruction syndrome (SOS) has been rarely studied after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective multicentre study on patients with SOS after allo-HSCT in China. The incidence, risk factors, and outcomes were compared between HID HSCT and matched related donor (MRD) HSCT. SOS developed in 0.4% of patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1-55) after allo-HSCT (HIDs: 24 days, MRDs: 20 days, p = 0.316). For patients diagnosed with SOS, the 2-year cumulative incidence of relapse was 22.7% and 22.4% in patients receiving HID and MRD transplantation, respectively (p = 0.584). Overall survival (OS) at 2 year was 10.4% and 38.5% in the two groups (p = 0.113). The transplant-related mortality (TRM) at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analyses, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and advanced disease status at the time of HSCT (p = 0.009). The outcomes of SOS after HID HSCT are similar to those after MRD HSCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doadores de Tecidos , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , China/epidemiologia , Feminino , Seguimentos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.
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Citotoxicidade Imunológica , Linfócitos T Citotóxicos , Perforina/genética , Perforina/metabolismo , Proteínas Citotóxicas Formadoras de Poros/genéticaRESUMO
To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.
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Medula Óssea , Proteômica , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Medula Óssea/imunologia , Proteômica/métodos , Idoso , Adulto Jovem , Contagem de PlaquetasRESUMO
Bronchiolitis obliterans syndrome (BOS) is a common and potentially devastating noninfectious pulmonary complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, predictive tools for BOS are not available. We aimed to identify the clinical risk factors and establish a prognostic model for BOS in patients who undergo allo-HSCT. We retrospectively identified a cohort comprising 195 BOS patients from 6100 consecutive patients who were allografted between 2008 and 2022. The entire cohort was divided into a derivation cohort and a validation cohort based on the time of transplantation. Via multivariable Cox regression methods, declining forced expiratory volume at 1 s (FEV1) to <40%, pneumonia, cGVHD except lung, and respiratory failure were found to be independent risk factors for the 3-year mortality of BOS. A risk score called FACT was constructed based on the regression coefficients. The FACT model had an AUC of 0.863 (95% CI: 0.797-0.928) in internal validation and 0.749 (95% CI: 0.621-0.876) in external validation. The calibration curves showed good agreement between the FACT-predicted probabilities and actual observations. The FACT risk score will help to identify patients at high risk and facilitate future research on developing novel, effective interventions to personalize treatment.
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Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Transplante de Células-Tronco Hematopoéticas , Humanos , Bronquiolite Obliterante/terapia , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de RiscoRESUMO
Septic shock remains a potentially life-threatening complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. There is a paucity of information on the clinical characteristics, outcome and prognostic factors of septic shock patients after allo-HSCT. We aimed to describe the clinical characteristics of septic shock after allo-HSCT and its associated health outcomes and to evaluate the role of patient demographics, transplantation-related laboratory and clinical variables associated with the short-term mortality of septic shock after allo-HSCT. We retrospectively studied 242 septic shock patients from 6105 consecutive patients allografted between 2007 and 2021. We assessed 29 risk factors as candidate predictors and used multivariable logistic regression to establish clinical model. The primary outcome was 28-day mortality. The median age of the subjects was 34 (IQR 24 to 45) years. A total of 148 patients (61.2%) had positive blood cultures. Gram-negative bacilli accounted for 61.5% of the positive isolates, gram-positive cocci accounted for 12.2%, and fungi accounted for 6.1%. Coinfections were found in 30 (20.3%) patients. Escherichia coli was the dominant isolated pathogen (31.1%), followed by Pseudomonas spp. (12.8%) and Klebsiella pneumoniae (10.1%). With a median follow-up of 34 (IQR: 2 to 528) days, a total of 142 (58.7%) patients died, of whom 118 (48.8%) died within the first 28 days after septic shock diagnosis, 131 (54.1%) died within 90 days, and 141 (58.3%) died within 1 year. A large majority of deaths (83.1% [118/142]) occurred within 28 days of septic shock diagnosis. Finally, 6 independent predictive variables of 28-day mortality were identified by multivariable logistic regression: time of septic shock, albumin, bilirubin, PaO2/FiO2, lactate, and sepsis-induced coagulopathy. Patients with late onset shock had higher 28-day mortality rates (64.6% versus 25.5%, P < .001) and more ICU admission (32.6% versus 7.1%, P < .001) than those with early onset shock. We highlight the poor survival outcomes in patients who develop septic shock, emphasizing the need for increasing awareness regarding septic shock after allo-HSCT. The information from the current study may help to assist clinicians in identifying high-risk patients.
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Transplante de Células-Tronco Hematopoéticas , Choque Séptico , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Prognóstico , Choque Séptico/etiologia , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Due to the concern of fratricide, clinical development of CAR T cells for the therapy of T cell malignancies lags behind that for B cell malignancies. Attempts are being made to revise T cell biomarkers so that the re-engineered CAR T cells can target T cell malignancies. CD3 and CD7 are the two pan-T cell surface biomarkers that have been either knocked out or knocked down through genome base- editing technology or by protein expression blockers so that the re-engineered T cells can target T cells without fratricide. We summarized several latest reports on the CAR T cells for the therapy of T cell leukemia /lymphoma from the 2022 ASH Annual Meeting, with latest updates on clinical trials of TvT CAR7, RD-13-01, and CD7 CART.
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Leucemia de Células T , Leucemia , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Imunoterapia AdotivaRESUMO
Clearance of hepatitis B surface antigen (HBsAg) is an ideal therapeutic goal for patients with chronic hepatitis B virus (HBV) infection. Haematopoietic stem cell transplantation (HSCT) is the most effective therapy for a variety of haematological diseases. For patients with chronic HBV infection who received allo-HSCT, recipient hepatitis B serological status might change after allo-HSCT; however, data on the loss of HBsAg following allo-HSCT are relatively rare. We first reviewed patients with chronic HBV infection who received allo-HSCT in our centre from 2010 to 2020, and 125 patients were included in our study. A total of 62 patients (49.6%) with chronic HBV infection achieved HBsAg loss after allo-HSCT. Positivity for HBeAb and HBsAb in donors as well as no cytomegalovirus (CMV) infection were identified as independent risk factors for HBsAg loss after allo-HSCT. A predictive model including positivity for HBeAb and HBsAb in donors and no CMV infection was subsequently developed and performed well with effective discrimination and calibration. In addition, patients could benefit when this model is used in the clinic, as revealed via decision-curve analysis (DCA). However, multicentre prospective studies are required for validation.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Hepatite B Crônica , Hepatite B , Humanos , Antígenos de Superfície da Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Anticorpos Anti-Hepatite B , Infecções por Citomegalovirus/etiologiaRESUMO
Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopênica Idiopática/complicações , Qualidade de Vida , Estudos Retrospectivos , Estudos Prospectivos , Hemorragia/diagnóstico , Trombocitopenia/complicaçõesRESUMO
Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.
Assuntos
Púrpura Trombocitopênica Idiopática , Adulto , Hemorragia Cerebral/complicações , Escala de Coma de Glasgow , Humanos , Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/epidemiologia , Curva ROCRESUMO
Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.