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  • American Society of Hematology  (2)
  • Mo, Xiao-Dong  (2)
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  • American Society of Hematology  (2)
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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 13-13
    Abstract: Introduction Immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission. Methods This open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts & lt;30×10 9/L, or & lt; 50×10 9/L and significant bleeding symptoms (World Health Organization bleeding scale ≥ 2). Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral tacrolimus (initial 0.03 mg/kg/day and maintain blood concentration at 3-5 ng/mL for 12 weeks) plus high-dose dexamethasone (HD-DXM) or HD-DXM monotherapy for 12 weeks. DXM (40 mg) was administered orally daily for 4 consecutive days to both study arms. The 4-day course of DXM was repeated on days 11-14 in patients who lacked response by day 10. The primary endpoint was 6-month sustained response (SR), defined as platelet count maintained & gt;50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080). Results Total 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups. Conclusions Low-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: It includes information or discussion of off-label drug use of tacrilimus.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2113-2113
    Abstract: Introduction Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been demonstrated to be the most effective therapy for various malignant as well as nonmalignant haematological diseases. The wide use of allo-HSCT has inevitably led to a variety of complications after transplantation, with bleeding complications such as disseminated intravascular coagulation (DIC). DIC accounts for a significant proportion of life-threatening bleeding cases occurring after allo-HSCT. However, information on markers for early identification remains limited, and no predictive tools for DIC after allo-HSCT are available. This research aimed to identify the risk factors for DIC after allo-HSCT and establish prediction models to predict the occurrence of DIC after allo-HSCT. Methods The definition of DIC was based on the International Society of Thrombosis and Hemostasis (ISTH) scoring system. Overall, 197 patients with DIC after allo-HSCT at Peking University People's Hospital and other 7 centers in China from January 2010 to June 2021 were retrospectively identified. Each patient was randomly matched to 3 controls based on the time of allo-HSCT (±3 months) and length of follow-up (±6 months). A lasso regression model was used for data dimension reduction, feature selection, and risk factor building. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated the clinical risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal and external validation was assessed. Various machine learning models were further used to perform machine learning modeling by attempting to complete the data sample classification task, including XGBClassifier, LogisticRegression, MLPClassifier, RandomForestClassifier, and AdaBoostClassifier. Results A total of 7280 patients received allo-HSCT from January 2010 to June 2021, and DIC occurred in 197 of these patients (incidence of 2.7%). The derivation cohort included 120 DIC patients received allo-HSCT and 360 patients received allo-HSCT from Peking University People's Hospital, and the validation cohort included the remaining 77 patients received allo-HSCT and 231 patients received allo-HSCT from the other 7 centers. The median time for DIC events was 99.0 (IQR, 46.8-220) days after allo-HSCT. The overall survival of patients with DIC was significantly reduced (P < 0.0001). By Lasso regression, the 10 variables with the highest importance were found to be prothrombin time activity (PTA), shock, C-reactive protein, internationalization normalized ratio, bacterial infection, oxygenation, fibrinogen, blood creatinine, white blood cell count, and acute respiratory distress syndrome (from highest to lowest). In the multivariate analysis, the independent risk factors for DIC included PTA, bacterial infection and shock (P & lt;0.001), and these predictors were included in the clinical prediction nomogram. The model showed good discrimination, with a C-index of 0.975 (95%CI, 0.939 to 0.987 through internal validation) and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (C-index, 0.778 [95% CI, 0.759 to 0.766]) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. The predictive value ROC curves of different machine learning models show that XGBClassifier is the best performing model for this dataset, with an area under the curve of 0.86. Conclusions Risk factors for DIC after allo-HSCT were identified, and a nomogram model and various machine learning models were established to predict the occurrence of DIC after allo-HSCT. Combined, these can help recognize high-risk patients and provide timely treatment. In the future, we will further refine the prognostic model utilizing nationwide multicenter data and conduct prospective clinical trials to reduce the incidence of DIC after allo-HSCT and improve the prognosis. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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