High-dose Dexamethasone Therapy Research Articles

Obesity is associated with poor outcomes of corticosteroid treatment in patients with primary immune thrombocytopenia.

Emerging evidence has demonstrated that obesity impacts multiple immune-related diseases. It remains unclear whether and how obesity alters treatment outcomes in patients with primary immune thrombocytopenia (ITP). Thus, we retrospectively investigated 214 treatment-naïve patients who received standard high-dose dexamethasone therapy in Qilu Hospital. Patients with obesity showed significantly lower overall initial response (underweight vs. normal vs. overweight vs. obese: 85.7% vs. 85.2% vs. 72.0% vs. 52.3%, p = 0.001) and initial complete response ([CR], 71.4% vs. 70.4% vs. 53.3% vs. 27.3%, p < 0.001) rates. The same trend was observed in the 6-month sustained response (63.6% vs. 52.3% vs. 35.6% vs. 22.7%, p = 0.03) and sustained CR (36.4% vs. 44.6% vs. 24.4% vs. 9.1%, p = 0.01). The Kaplan-Meier analysis revealed a shortened duration of remission in the obese group (median duration of remission, not reached vs. 16 months vs. 2 months vs. 1 month, p = 0.002). In multivariate regression analysis, obesity was independently associated with poor initial and sustained responses, and an increased risk for relapse. In conclusion, obesity is a negative predictor for outcomes of corticosteroid treatment. A stratified strategy according to body mass index status may facilitate the precision management of ITP.

A Case of Off-Pump Coronary Artery Bypass Grafting Following High-Dose Dexamethasone Therapy in a Patient with Idiopathic Thrombocytopenic Purpura

A Case of Off-Pump Coronary Artery Bypass Grafting Following High-Dose Dexamethasone Therapy in a Patient with Idiopathic Thrombocytopenic Purpura

Oral pulsed high-dose dexamethasone therapy for rheumatic diseases: An alternative safe and effective scheme

Oral pulsed high-dose dexamethasone therapy for rheumatic diseases: An alternative safe and effective scheme

Effects of Early Initiation of High-Dose Dexamethasone Therapy on Pro-Inflammatory Cytokines and Mortality in LPS-Challenged Mice.

This study aims to explore the effects of early dexamethasone therapy at low to high doses on the survival and inflammatory responses in lipopolysaccharide (LPS)-challenged mice. We performed two-series experiments to explore the impact of early dexamethasone therapy at different doses (0.5 mg/kg, 1.5 mg/kg, and 5 mg/kg; PO) on pro-inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as survival in LPS-treated mice (10 mg/kg, IP). Dexamethasone was administered daily from 24 h before and 5 days after LPS challenge. Dose-dependent improved survival was demonstrated with dexamethasone (p < 0.05). Body weight was significantly decreased within 24 h of LPS injection, with significantly greater weight loss in the dexamethasone groups (p < 0.05). Weight changes were significantly associated with the days after LPS administration (p < 0.01), but not with the dexamethasone dose (p > 0.05). Mice treated with high-dose dexamethasone (5 mg/kg) had a significantly lowered serum TNF-α (134.41 ± 15.83 vs. 408.83 ± 18.32) and IL-6 (22.08 ± 4.34 vs. 91.27 ± 8.56) compared with those without dexamethasone. This study provides essential insights that the suppression of early-phase hyperactivation of pro-inflammatory activities through the early initiation of high-dose dexamethasone therapy increases sepsis-related prognosis.

A study on high-dose dexamethasone versus prednisolone as frontline therapy in newly diagnosed immune thrombocytopenia in children

Objectives: Treatment for children with newly diagnosed immune thrombocytopenia (ITP) includes corticosteroids, out of which prednisolone is commonly used. High-dose dexamethasone (HD-DXM) treatment for children with newly diagnosed ITP can produce better outcomes than prednisone, as stated by many studies. A few articles compare HD-DXM and prednisolone as frontline therapies in newly diagnosed adult ITP but data on pediatric ITP comparing these two drugs are scarce. Material and Methods: It was a randomized, prospective, and cohort study. After enrolment, checking the inclusion and exclusion criteria, each child was randomly distributed into two groups; one cohort was treated with HD-DXM in the dose of 40 mg/m2 (maximum daily dose 40 mg) for 4 days once every 28 days for three cycles; and one with prednisolone in the dose of 2 mg/kg/day (maximum 60 mg/day) for 2 weeks, with quick tapering. A total of 42 children were enrolled, 21 in each cohort. Results: The overall response (OR) was 42.9% with HD-DXM therapy. The OR and median time to response were similar in both HD-DXM and prednisolone cohorts. There was also no significant difference in incidences of adverse effects between the two cohorts. Conclusion: Thus, this study confirms that HD-DXM is a safe, effective, and non-inferior option compared to prednisolone as frontline therapy in newly diagnosed ITP in children.

High-dose methylprednisolone versus dexamethasone therapy for hospitalized patients with severe COVID-19: a retrospective analysis

This study aimed to evaluate the clinical effects of high-dose methylprednisolone therapy in hospitalized patients with severe coronavirus disease (COVID-19) who required oxygen therapy, but not noninvasive/invasive mechanical ventilation or extracorporeal membrane oxygenation therapy. This retrospective observational study that was conducted from April 2021 to October 2021 at a secondary hospital in Japan enrolled patients who were administered 6 mg/day dexamethasone as an initial corticosteroid treatment on admission (dexamethasone group) and those who were administered ≥ 250 mg/day methylprednisolone (methylprednisolone group). Of the 42 participants, 40.5%(17/42) were included in the methylprednisolone group. The incidence of transfer to a tertiary hospital did not differ significantly between the methylprednisolone and dexamethasone groups (5.9% vs. 20%, p = 0.37), and in-hospital mortality was similar in both the groups (0% vs. 4%, p = 1.00). Participants in the methylprednisolone group had a significantly longer duration of oxygen therapy than the dexamethasone group (median (interquartile range) 8.5 (5.5–11.2) days vs. 4 (2.0–7.5) days, p &lt; 0.05). Compared to dexamethasone, high-dose methylprednisolone therapy did not provide any added benefits for patients with severe COVID-19 who did not require respiratory mechanical support.

CARDIAC TAMPONADE AS A PRESENTING FEATURE OF METASTATIC GI CARCINOMA

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disease. It is characterized by abnormalities in immunoregulation due to a non-malignant proliferation of lymphocytes and secretion of inflammatory cytokines. HLH is typically associated with acquired immunodeficiencies such as in hematopoietic stem cell transplantation. We present a case of a young woman who was treated in our ICU for confirmed HLH which was attributed to an Epstein-Barr virus (EBV) infection that reactivated during her post-transplant immunosuppression. CASE PRESENTATION: A 46-year-old female presented to her primary care physician with gradual dyspnea, spontaneous gum bleeding and lower extremity bruising. She was diagnosed with anemia during her pregnancy. Eventually developed leukopenia and pancytopenia. She was later diagnosed with aplastic anemia and underwent a conditioning regimen prior to peripheral blood stem cell transplantation (PBSCT) with cyclophosphamide, fludarabine, total body irradiation, and rabbit anti-thymocyte globulin (ATG). She had an allogeneic PBSCT from a 10/10 HLA-matched unrelated donor (MUD). Her pre-transplant workup was positive EBV IgG. Donor pre-transplant workup was negative for EBV. Post-transplant immunosuppression consisted of rituximab and tacrolimus. Two months post-transplant, she was admitted for non-neutropenic fevers and diagnosed with Clostridium difficile colitis, acute kidney injury, EBV viremia (>800000 IU/ml), and widespread lymphadenopathy concerning for EBV-associated biopsy proven monomorphic PTLD. She was treated with two doses of Rituximab. Due to worsening encephalopathy, liver function tests and metabolic acidosis, ICU transfer initiated for continuous renal replacement therapy (CRRT). She developed acute respiratory failure and septic shock; was intubated, requiring vasopressors. During her ICU stay, HLH was considered. Bone marrow aspiration and biopsy performed confirmed HLH. High dose dexamethasone therapy was initiated. She also received two doses of Etoposide and a dose of tocilizumab in ICU. She was successfully extubated to high flow nasal cannula. Next Day, given her worsening mental status; Emapalumab (GAMIFANT, Novimmune SA), a fully human anti–IFN-gamma monoclonal antibody for HLH, was administered. Her cognitive function further declined, and she progressed to multiorgan failure and death. DISCUSSION: Aplastic anemia is a hematologic disorder characterized by pancytopenia and bone marrow aplasia. Bone marrow transplantation and immunosuppressive therapy are the modalities currently used, with success rates ranging 60% to 80%. Most treatment options for EBV-HLH have unclear effectiveness in adults. CONCLUSIONS: Despite trying rituximab, dexamethasone, etoposide, tocilizumab and Emapalumab, our transplant patient exhibits a unique and ambiguous intersection of EBV-associated refractory HLH, unresponsive to treatments. REFERENCE #1: Imashuku S, Kuriyama K, Sakai R, Nakao Y, Masuda S, Yasuda N, et al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med Pediatr Oncol. 2003;41(2):103-9. REFERENCE #2: Fox CP, Shannon-Lowe C, Gothard P, Kishore B, Neilson J, O'Connor N, et al. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults characterized by high viral genome load within circulating natural killer cells. Clin Infect Dis. 2010;51(1):66-9. REFERENCE #3: Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, et al. Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020;382(19):1811-22. DISCLOSURES: No relevant relationships by Padmastuti Akella, source=Web Response No relevant relationships by Saira Imran, source=Web Response No relevant relationships by Aizaaz Khan, source=Web Response No relevant relationships by Kevin Lazo, source=Web Response

Immune Thrombocytopenia Exacerbation After COVID-19 Vaccination in a Young Woman

The coronavirus disease 2019 (COVID-19) pandemic is one of the greatest health concerns worldwide. Safe and effective COVID-19 vaccines are urgently needed and have been rapidly approved. COVID-19 vaccine-induced thrombocytopenia was reported as a rare adverse effect in the Vaccine Adverse Events Reporting System. A 25-year-old woman, who was previously diagnosed with immune thrombocytopenia (ITP, stage I), had exacerbated severe thrombocytopenia (platelet count of 6,000/μL) with a headache, joint pain, general fatigue, and bleeding tendency three days after receiving her second dose of the Pfizer BioNTech COVID-19 vaccine. Pulsed high-dose dexamethasone therapy rapidly ameliorated the ITP. Although it is difficult to confirm a causal association between Pfizer BioNTech COVID-19 vaccination and ITP exacerbation, abrupt onset of ITP exacerbation after vaccination suggests that the ITP may be vaccination-induced thrombocytopenia exacerbation. Rare but severe adverse events such as ITP may be observed, depending on increased numbers of individuals who receive COVID-19 vaccines worldwide. Further investigation is needed to clarify the mechanisms of COVID-19 vaccine-induced ITP.

Front-Line Treatment in Immune Thrombocytopenia Using Eltrombopag and High-Doses of Dexamethasone, Long-Term Follow-up

▪IntroductionPrimary immune thrombocytopenia (ITP) is an autoimmune disease that results in platelet destruction as well as suppression in its production. There are a large number of therapeutic options, however, achieving a long-term and safe response has been the subject of study. As front-line therapies, gammaglobulin and corticosteroids are the most common treatments, however our group reported the use of eltrombopag and high doses of dexamethasone in the first line of treatment. In this study update we propose to inform the combined effectiveness of eltrombopag and dexamethasone at high doses as first line with a median follow-up of 4 years.Material and methodsA prospective longitudinal single arm study was performed in patients with ITP at the University Hospital “Dr. José Eleuterio González ”in Monterrey Mexico and of the Clinic Ruiz in Puebla, Mexico. Patients older than 18 years, with bleeding manifestations and platelet count <30 x 109 / L without previous treatment were included. Treatment consisted of eltrombopag (50 mg daily, day 1-28) in addition to dexamethasone (40 mg PO, day 1-4) on an outpatient basis. A platelet count> 30 x 109 / L and complete response (CR)> 100 x 109 / L was considered partial response (PR). Relapse-free survival was considered from the initial response day until the presence of relapse <30 x 109 / L and the duration of the response as the maintenance period of the PR or CR.ResultsWe included 9 patients from June 2012 to July 2013. The median follow-up was 41 months (10-51). At diagnosis, the median platelet count was 23.4 x 109 (2-30) and at the end of follow-up was 89 x 109 (65-282). Currently 5 patients (55.6%) maintained CR and 4 (44.4%) PR. Three patients relapsed during follow-up at a median of 7 months (1-14), of whom 2 achieved PR and 1 CR subsequently. The relapse free survival (RFS) was 64% at 2 years. There were no manifestations of bleeding, no events of myelofibrosis or venous thrombosis were recorded and treatment was well tolerated.CONCLUSIONSCombined eltrombopag and high-dose dexamethasone therapy is a viable first-line option in ITP that can generate sustained complete long-term response in adult patients. Clinical trials with larger numbers of samples are required, as well as randomized comparative studies. DisclosuresHerrera-Rojas:JANSSEN: Consultancy, Employment, Honoraria, Speakers Bureau. Gomez-Almaguer:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.

Erratum.

Erratum to "High-dose Dexamethasone Therapy as the Initial Treatment for Idiopathic Thrombocytopenic Purpura: Protocol for a Multicenter, Open-label, Single Arm Trial" Vol.72, No.2, pp197-201.

Clinical Efficacy and Safety of High-Dose Dexamethasone Plus Low-Dose Rituximab as First-Line Therapy in Newly Diagnosed Primary Immune Thrombocytopenia.

Standard-dose prednisone as first-line therapy for primary immune thrombocytopenia (ITP) can not obtain high long-term responses. Results from high-dose dexamethasone course administered in adult newly diagnosed ITP were promising. The role of standard-dose rituximab in first-line treatment of newly diagnosed ITP were also investigated. We retrospectively analyzed the efficacy and safety of high-dose dexamethasone plus low-dose (100mg/w) rituximab for treatment of adults newly diagnosed ITP. A total of eighteen patients received dexamethasone 40mg/day for 4 consecutive days (days + 1 to + 4), rituximab 100mg once weekly for a total of 4weeks (days + 7, + 14, + 21 and + 28). Non-responders accepted the repeated dexamethasone treatment every 2weeks for a total of up to 3 treatment cycles. The overall response was 100% at 28th day. Median follow-up was 17months (1-33months). Six patients (33.3%) relapsed. Sustained complete response or response after 6months and 12months of follow-up were reached in 83.3% (15/18) and 61.5% (8/13) of patients respectively. The 12-month and 15-month cumulative relapse-free survival were 69.3% and 60.7%. Incidence of adverse effects was 11.1% (2/18). High-dose dexamethasone plus low-dose rituximab therapy had high efficacy and well tolerability as first-line treatment option in newly diagnosed ITP.

High-Dose Dexamethasone Corrects the Elevated Level of IL-16 in Immune Thrombocytopenia

Introduction: Adult primary immune thrombocytopenia (ITP) is an autoimmune-mediated haemorrhagic disorder characterized by excessive platelet destruction and decreased platelet production. ITP patients have a Th1 dominant profile, which was involved in the pathogenesis of ITP. Interleukin-16 (IL-16) can directly affect cellular or humoral immunity by mediating the cellular cross-talk among T cells, B cells and dendritic cells. Several studies have focused on IL-16 as an immunomodulatory cytokine that takes part in Th1 polarization in autoimmune diseases, but the roles of IL-16 in ITP remain unknown. Treatment with high-dose dexamethasone (HD-DXM) as a single-agent for four days has been widely recognized as the first-line therapy for ITP patients in need of clinical management. The aim of this study is to investigate the roles of IL-16 and effect of HD-DXM on IL-16 in ITP.Methods: We investigated the differences in IL-16 expression in the bone marrow and peripheral blood between ITP patients and healthy controls by ELISA. The mRNA expression of pro-IL-16, caspase-3 and T-bet in active ITP patients and healthy controls were quantified by real-time PCR. Furthermore, we detected changes in IL-16 concentration and gene expression before and after the 4-day HD-DXM therapy. Bone marrow samples were obtained from 23 patients and 10 healthy bone marrow donors, and peripheral blood samples were obtained from 64 patients (among them, 21 received single-agent HD-DXM therapy, the peripheral blood samples were obtained before HD-DXM therapy and 28 days after HD-DXM administration) and 38 healthy blood donors. Adult primary ITP patients with active disease were enrolled in this study between May 2015 and January 2018 at the Department of Haematology, Qilu Hospital, Shandong University, Jinan, China.Results: The concentration of IL-16 in the bone marrow supernatants and plasma of active ITP patients was significantly higher compared with that of the healthy controls (P < 0.05) (Fig. 1A, B). Gene expression of pro-IL-16 and caspase-3 in bone marrow mononuclear cells (BMMCs) in ITP patients elevated compared with healthy controls (P < 0.05) (Fig. 2A). Besides, gene expression of pro-IL-16, caspase-3 and T-bet in peripheral blood mononuclear cells (PBMCs) in ITP patients elevated (P < 0.05) (Fig. 2B). Among the 21 patients which received single-agent HD-DXM therapy, 18 responded effectively to the HD-DXM therapy according to the standard definition. The post-treatment plasma (n=21) IL-16 level decreased significantly compared with that of pre-treatment level (P < 0.05), and the level of IL-16 in the plasma of ITP patients before and after HD-DXM treatment was significantly higher than that of healthy controls (P < 0.05) (Fig. 1C). There was no correlation between IL-16 levels in the bone marrow supernatant or plasma and platelet count (data not shown). In addition, pro-IL-16, caspase-3, T-bet mRNA expression was significantly decreased after treatment with HD-DMX (P < 0.05) (Fig. 2C), although the corresponding values in patients were not statistically higher than those of healthy controls. The correlation between the plasma IL-16 concentration and pro-IL-16, caspase-3 and T-bet mRNA levels was also analysed in ITP patients (n = 21). The results demonstrated that the mRNA levels of the three detected factors were positively correlated with plasma IL-16 concentration (r2 = 0.5846, P < 0.05, r2 = 0.3980, P < 0.05 and r2 = 0.3145, P <0.05 for pro-IL-16, caspase-3 and T-bet, respectively) (Fig. 2D-F).Conclusions: ITP is an autoimmune disorder; complex interactions among antigen-presenting cells, T cells and B cells are pivotal to its pathogenesis. Our data suggest that IL-16 plays an important role in the pathogenesis of ITP by polarization of Th1. Furthermore, by modulating the abnormal IL-16 level associated with the Th1 imbalance via treatment with pulsed HD-DXM provided us with new insights into the immune regulatory mechanisms for the treatment of ITP. In our future study, we will use an in vitro study system to test and verify if the anti-IL-16 antibody can be used to treat adult ITP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Efficacy of High Dose Dexamethasone Therapy in Children with Immune Thrombocytopenic Purpura

The Efficacy of High Dose Dexamethasone Therapy in Children with Immune Thrombocytopenic Purpura

High dose dexamethasone as an alternative rescue therapy for active bleeding in children with chronic ITP: clinical and immunological effects

High-dose dexamethasone (HD-DXM) is debated as a second-line therapy for chronic Immune thrombocytopenia (ITP) in children. The aim of this study is to evaluate the efficacy and safety of HD-DXM as an emergency therapy in uncontrolled bleeding in children with chronic ITP and to assess its immunological effect on dendritic cells (DCs) percentage and their co-stimulatory markers CD86 and CD83.Totally, 20 children previously diagnosed as chronic ITP were enrolled in this study and all admitted to hospital with uncontrolled bleeding. Patients received HD-DXM as a single daily dose for 4 days. Blood samples were withdrawn from patients just prior to HD-DXM therapy and on day 5 to evaluate the platelet count and for flowcytometric analysis of DCs. Daily assessment of bleeding severity was performed. The platelet counts significantly increased in patients after 5 days of initiation of therapy compared with platelet count before therapy (p-value = 0. 0002). Control of bleeding observed in (90%), complete response (CR) documented in (50%), response (R) documented in (40%), and no response (NR) documented in (10%) of patients. The time to respond was raging from 1 to 3 days and minor complication recorded in two patients. Both plasmacytoid DCs and myeloid DCs percentage and their expression of co-stimulatory markers, CD86 and CD83 decreased significantly after HD-DXM therapy. Conclusion: short course of HD-DXM as a rescue therapy seems to be an effective alternative emergency treatment for uncontrolled bleeding in chronic ITP children especially in nations with limited resources.

Pulsed High-dose Dexamethasone Therapy and Its Application in Children with Immune Thrombocytopenia-Review

Immune thrombocytopenia (ITP) is the most common immune-mediated acquired bleeding disorders in children. The prognosis of majority of these patient are well, with recent complete remission. However, a few patients are facing the risk of bleeding since they do not respond to the first-line therapy, and need second-line therapy. The present second-line treatments are difficult to be popularized due to their efficacy, side-effects, costs and some other factors. The pulsed high-dose dexamethasone (HDD) therapy with its good effect, small adverse effects and low cost in adults has been used as the first-line therapy in newly diagnosed ITP, which now has attracted the attention of pediatricians. In this review, we briefly summarized the latest progress of pulsed HDD therapy for ITP in children.

Abstract CT115: Pharmacokinetics of standard versus short high-dose dexamethasone therapy in childhood acute lymphoblastic leukemia: results from the UKALL 2011 trial

Abstract Dexamethasone (Dex) is a key component of ALL therapy, with glucocorticoid sensitivity strongly linked to prognosis. However, it also contributes to life threatening toxicities. The ongoing UKALL 2011 trial is investigating a new schedule of Dex (10mg/m2 × 14 days vs 6mg/m2 × 28 days), in an attempt to bring about a more rapid cytoreduction whilst limiting toxicities associated with long term steroid exposure. There are limited data regarding Dex pharmacokinetics, however large variability has been reported in children with ALL (Yang et al. 2008). For Dex pharmacokinetic studies, blood samples were collected up to 8h post oral administration on one of the first and last three days of induction chemotherapy. Plasma Dex levels were analysed using a validated LC-MS method, with a range of 5-250ng/ml, and non-compartmental pharmacokinetic analysis was performed. Pharmacokinetic parameters from day one sampling are shown below. Exposure, as defined by AUC0-12h, and Cmax were significantly higher on the short arm (p = 0.0002 and 0.0007, respectively). However there was substantial overlap between the two arms, with a number of patients on the standard arm exhibiting higher exposures than those on short therapy, despite having a longer duration of treatment. This is reflected in the AUC0-12h ranges observed on the two arms (short: 202-1606; standard: 38-1009 hr*ng/mL). Pharmacokinetic profiles also differed between the two days of treatment, with AUC0-12h being significantly higher at the end of induction chemotherapy (n = 37, study day 1: 655 ± 322; study day 2: 894 ± 496 hr*ng/mL, p = 0.003). Based on these preliminary data it will be important to consider pharmacokinetic variability when analysing the results generated from the UKALL 2011 trial. Further evaluation of relationships between pharmacokinetic variation, dose scheduling and clinical outcome may enable better stratification of Dex therapy for future patients. Dexamethasone pharmacokinetics in short and standard therapy arms following day one samplingPharmacokinetic parameters (mean ± SD)Half life (hr)Tmax (hr)Cmax(ng/mL)Clearance(L/hr/m2)AUC0-12h(hr*ng/mL)Short (n=43)3.96 ± 3.21.9 ± 1.0128 ± 558.1 ± 5.3692 ± 325Standard (n=33)3.68 ± 2.11.7 ± 1.187 ± 419.2 ± 12.7443 ± 202 Citation Format: Rosanna K. Jackson, Julie AE Irving, Gareth J. Veal. Pharmacokinetics of standard versus short high-dose dexamethasone therapy in childhood acute lymphoblastic leukemia: results from the UKALL 2011 trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT115.

Toxic epidermal necrolysis: 13 years of experience in the management at a Department of Dermatology in China

Objective: The study aimed to investigate the efficacy of our therapeutic options on toxic epidermal necrolysis (TEN) patients.Methods: After giving informed consent, patients affected by TEN were included in the study between January 2001 and December 2013. Suspected causative drugs, onset to hospitalization, complications, management, outcome, laboratory investigations of blood tests and therapeutic options were recorded and analyzed. SCORTEN scoring system was used to evaluate the complications and the survival rate. Therapeutic interventions included immediate withdrawal of any potentially fatal drug, nursing care, supportive therapy, high-dose corticosteroids, antibiotics, plasma therapy, intravenous immunoglobulins (IVIG) and traditional Chinese medicine (TCM). Blood tests were taken as a result of clinical outcome.Results: Total 21 consecutive patients (10 males and 11 females, mean age 33 years) were included in the study. Cefalexin, paracetamol, quick cold capsules, compound aminopyrine phenacetin tablets, carbamazepine, propylthiouracil, sulfonamide, ampicillin, and phenylbutazone were suspected to be the causative agents. All patients received high-dose dexamethasone or methylprednisolone therapy. Eighteen patients received the administration of antibiotics. Twelve patients received plasma infusions, and 11 patients were given albumin. Only 2 patients applied IVIG. Additionally, 3 and 14 cases were intravenously injected with QKL and Xiyanping, respectively. The average score of SCORTEN was 2.52 and the average percentage of total body surface area was 68.8%. The mortality rate in our study was 19%.Conclusion: The therapeutic options in our study, including nursing care, corticosteroid, anti-inflammatory and TCM are effective for the treatment of TEN.

Thromboprophylaxis in Multiple Myeloma Patients Treated with Lenalidomide - a Systematic Review

BackgroundLenalidomide in combination to steroid therapy, including high-dose dexamethasone (RD), low-dose dexamethasone (Rd) or triple therapy of melphalan, prednisolone, lenalidomide (MPR), has shown to be an effective and well-tolerated treatment for patients with newly diagnosed multiple myeloma (NDMM) and relapsed refractory multiple myeloma (RRMM). Lenalidomide is associated with an increased risk of venous thromboembolism, and studies have consistently demonstrated the need for venous thromboembolism (VTE) prophylaxis in patients receiving these combinations. However, the optimal approach to thromboprophylaxis has not yet been established.ObjectiveIn this systematic review we sought to compare the efficacy of aspirin (ASA) or low molecular weight heparin (LMWH) in the prevention of VTE in patients with myeloma using lenalidomide- based therapy.MethodsA systematic literature search strategy was used to identify potential studies on MEDLINE, EMBASE, and CENTRAL using an OVID interface. The methodological quality of the selected cohort studies was assessed according to Newcastle-Ottawa Quality Assessment Scale, and risk of bias of randomised controlled trials (RCTs) was assessed according to risk of bias assessment tool from the Cochrane Handbook. The primary outcome measure was the incidence rate of VTE while using ASA or LMWH.ResultsOut of 247 studies, 6 met our inclusion criteria with a total of 1126 participants including a total of 5 phase III RCTs, and one retrospective study. Overall, all studies show high quality: In 4 of the 5 RCTs type of randomization was clearly reported, outcome assessment was blinded, and withdrawal rates were reported, and the remaining RCT was an abstract. In 4 RCTs the intervention and comparator arms were related to anti-myeloma treatment regimens.Pooled data of studies of NDMM treated with lenalidomide based regimen with ASA prophylaxis show a VTE rate of 98 of 915 (10.7%) [95% CI: 8.86-12.88] (Table1). In NDMM and RRMM patients treated with lenalidomide, VTE rate on LMWH prophylaxis was 3 of 211 (1.4%) [95% CI: 0.48-4.09] (Table2). The relative risk (RR) of VTE in patients receiving ASA compared to LMWH was 7.5 (95% CI: 2.41-23.53, p =0.0005).Overall, the rate of VTE was 1.4 (95% CI: 1.14 - 1.69) per 100 patient-cycles of anti-myeloma treatment. A subgroup analysis on patient using ASA showed a similar risk of 1.5 (95% CI: 1.24 - 1.84).The incidence of VTE in those using ASA while on RD was 52 of 195 (26.6%) [95% CI: 20.9-33.2], while VTE rate in those receiving Rd was 27 of 262 (10.3%) [95% CI: 7.18-14.58] demonstrating a statistically significant higher risk for patients on RD [RR=2.5 (95% CI: 1.68- 3.96), p <0.0001]. Furthermore, VTE rate with MPR therapy while on ASA was 19 of 458 (4.1%) [95% CI: 2.67-6.38]. Pooled data of studies revealed that patients who received lenalidomide and dexamethasone alone (RD+Rd) had a significantly higher risk of VTE compared to those on MPR while on ASA (RR=6.4 [(95% CI: 4.11- 9.91), p< 0.0001]).ConclusionThe study showed that the most frequent thromboprophylaxis of choice for patients with myeloma on lenalidomide-based therapy is ASA. However, ASA may not confer appropriate protection against VTE, especially in patients using high dose dexamethasone. On the other hand, the risk of VTE in patients receiving MPR and ASA was low and ASA may be a safe option for these patients. More studies comparing the safety of ASA to other anticoagulants such as LMWH or direct oral anticoagulants are warranted.Table 1Rate of VTE using ASA in NDMM with different lenalidomide based regimens. Rx: treatment; 95% CI: 95% confidence interval.StudyDesignRxNVTE rate: N (%)95% CIZonder, 2010 Rajkumar, 2010Phase III RCTRD19552 (26.6)20.9-33.2Larocca, 2011 Rajkumar, 2010Phase III RCTRd26227 (10.3)7.18-14.58Palumbo, 2012 Stewart, 2014Phase III RCTMPR45819 (4.1)2.67-6.38Total91598 (10.7)8.86-12.88Table 2Rate of VTE using LMWH in myeloma patients (NDMM or RRMM) on lenalidomide-based regimen. 95% CI: 95% confidence interval.PaperDesignInductionSettingNVTE rate: N (%)95% CIKlein, 2008Retrospective cohortRDRRMM451(2.2)0.39-11.57Larocca, 2011Phase III RCTRdNDMM1662(1.2)0.33-4.28Total2113(1.4)0.48-4.09 DisclosuresLouzada:pfizer: Consultancy, Other: advisory board and expert opinion; janssen: Consultancy, Other: advisory board and expert opinion; Celegene: Consultancy, Other: advisory board and expert opinion.

Decreased level of cytotoxic T lymphocyte antigen-4 (CTLA-4) in patients with acute immune thrombocytopenia (ITP)

IntroductionPreviously, we demonstrated the importance of T-cell immune response cDNA 7 (TIRC7) in acute immune thrombocytopenia (ITP). As the downstream molecule of TIRC7, cytotoxic T lymphocyte antigen-4 (CTLA-4) has been verified its negative regulation of acute ITP. This study aimed to investigate the exact role of CTLA-4 and its relationship with TIRC7 in acute ITP. Patients and methods37 patients with acute ITP were enrolled and received dexamethasone (40mg/day) for 4 consecutive days. Patients who had platelet counts more than 50×109/L or less were defined as responders or non-responders after treatment. The plasma, protein and mRNA levels of CTLA-4 and TIRC7 were monitored by ELISA, western blot and q-PCR, respectively. ResultsAfter high-dose dexamethasone therapy, CTLA-4 levels were significantly elevated not only in acute ITP patients (P<0.001; P<0.0001) but also in acute ITP responders (P<0.0001; P<0.0001). The levels of CTLA-4 were negatively correlated with the levels of TIRC7 before and after treatment; IFN-γ (Th1), IL-17 (Th17) and IL-22 (Th22) levels were all elevated, which were decreased after treatment not only in patients with acute ITP (P<0.01) but also in acute ITP responders (P<0.01). ConclusionsCTLA-4 level might reflect treatment efficacy and it might be associated with the pathogenesis of acute ITP.