Refractory Chronic Immune Thrombocytopenia Research Articles

The early and rapid response to daratumumab in children with chronic refractory immune thrombocytopenia from a referral single centre of China.

Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second-line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti-CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow-up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow-up end-point since the patient achieved response) was 48, 175 and 204 days with the follow-up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow-up. No significant treatment-related adverse events were found during follow-up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored.

Pediatric refractory chronic immune thrombocytopenia: Identification, patients' characteristics, and outcome.

Refractory chronic immune thrombocytopenia (r-cITP) is one of the most challenging situations in chronic immune thrombocytopenia (cITP). Pediatric r-cITP is inconsistently defined in literature, contributing to the scarcity of data. Moreover, no evidence is available to guide the choice of treatment. We compared seven definitions of r-cITP including five pediatric definitions in 886 patients with cITP (median [min-max] follow-up 5.3 [1.0-29.3] years). The pediatric definitions identified overlapping groups of various sizes (4%-20%) but with similar characteristics (higher proportion of immunopathological manifestations [IM] and systemic lupus erythematosus [SLE]), suggesting that they adequately captured the population of interest. Based on the 79 patients with r-cITP (median follow-up 3.1 [0-18.2] years) according to the CEREVANCE definition (≥3 second-line treatments), we showed that r-cITP occurred at a rate of 1.15% new patients per year and did not plateau over time. In multivariate analysis, older age was associated with r-cITP. One patient (1%) experienced two grade five bleeding events after meeting r-cITP criteria and while not receiving second-line treatment. The cumulative incidence of continuous complete remission (CCR) at 2 years after r-cITP diagnosis was 9%. In this analysis, splenectomy was associated with a higher cumulative incidence of CCR (hazard ratio: 5.43, 95% confidence interval: 1.48-19.84, p = 7.8 × 10-4). In sum, children with cITP may be diagnosed with r-cITP at any time point of the follow-up and are at increased risk of IM and SLE. Second-line treatments seem to be effective for preventing grade 5 bleeding. Splenectomy may be considered to achieve CCR.

Chronic refractory immune thrombocytopenia in adolescents and young adults.

Defining immune thrombocytopenia (ITP) in two age groups-children and adults-overlooks the specific clinical features and needs of adolescents and young adults (AYAS). We previously reported a high risk of chronic disease at 12 months (50%); however, data on the course of chronic ITP, the risk of refractoriness and treatment strategies in AYAS are limited. Data from patients aged 12-25 years with chronic primary ITP at 12 months were extracted from three large registries between 2004 and 2021. Clinical and laboratory data were evaluated until 48 months of follow-up (FU). Refractory ITP was defined as the administration of ≥3 different lines of therapy. A total of 427 AYAS (64% female) with chronic ITP were included. Overall, 7% and 14% were classified as 'refractory' at 12 and 48 months of FU respectively. The proportion of males was greater in the refractory group than in the non-refractory group (43% vs. 35%). AYAS with refractory disease displayed lower median platelet counts, more bleeding and a higher need for treatment at initial diagnosis and FU than non-refractory patients. This study reveals that refractory ITP is uncommon in AYAS; however, AYAS with refractory ITP display a high disease burden at all time points, including at initial diagnosis.

Therapeutic Outcomes of High Dose-Dexamethasone versus Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim Strategies in Persistent, Chronic, Refractory, and Relapsed Immune Thrombocytopenia Patients.

Primary immune thrombocytopenia (ITP) is an inflammatory autoimmune disease that can be managed with several treatment options. However, there is a lack of comparative data on the efficacy of these options in different phases of the disease. This study aimed to evaluate the efficacy of high-dose Dexamethasone (HD-DXM), Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim schedules in persistent, chronic refractory or relapsed Egyptian ITP patients with a platelet count ≤30 × 109/L. The primary outcome measure was a sustained increase in platelet counts over 50 × 109/L for an additional 12 months without additional ITP regimens. The study also aimed to identify a suitable treatment regimen with a long remission duration for each phase of ITP. Prednisolone + Azathioprine was significantly more effective in achieving an overall response in persistent patients than Romiplostim, high-dose Dexamethasone, and Rituximab. (90.9% vs. 66.6, [Odds ratio, OR: 5; confidence interval, CI 95% (0.866-28.86)], 45%, [OR: 0.082, CI 95% (0.015-0.448)] and, 25%, [OR: 30, CI 95% (4.24-211.8)], respectively, p-value < 0.01). Eltrombopag was significantly more effective in achieving a durable response in refractory ITP than HD-DXM, Rituximab, and Prednisolone; (80% compared to 32.2% [OR: 0.119, CI 95% (0.035-0.410)], 22.2% [OR:0.071, CI 95% (0.011-0.455)], and 18.1% [OR: 0.056, CI 95% (0.009-0.342)], respectively, p-value < 0.01). Finally, Eltrombopag following HD-DXM showed the highest percentage of patients with complete treatment-free survival times of at least 330 days. These findings could help clinicians choose the most appropriate treatment for their patients with ITP based on the phase of the disease. This trial is registered in clinicaltrials.gov with registration number NCT05861297.

Recent progress in immune thrombocytopenia pathophysiology and treatment

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction and impaired platelet production from bone marrow megakaryocytes. The details of different platelet destruction mechanisms resulting from differences in autoantibodies and autoantibody-independent direct platelet destruction remain unclear although antiplatelet autoantibodies directed against platelet glycoproteins, such as GPIIb/IIIa and GPIb, play a central role in ITP pathogenesis. ITP is diagnosed by excluding other causes of thrombocytopenia due to the lack of standard tests or biomarkers for its confirmation. Plasma thrombopoietin level measurement and reticulated platelet ratio are useful in distinguishing the cause of thrombocytopenia and will be included in the new "Diagnostic reference guide of adult immune thrombocytopenia." Currently, the treatment of refractory chronic ITP is mainly based on thrombopoietin receptor agonists, but ITP drugs with novel mechanisms of action are actively developed. New therapeutic agents are expected to be selected based on an accurate diagnosis and tailored to the pathophysiology of each case in ITP treatment.

Comparison of Response to Rituximab Therapy in Adults with Refractory Symptomatic Immune Thrombocytopenia According to the Presence of Accessory Spleen.

No data exist for the association between the presence of accessory spleen after splenectomy and response to rituximab in immune thrombocytopenia (ITP). We investigated the relationship between accessory spleen presence and rituximab response in splenectomized ITP patients. Fifteen chronic refractory ITP patients were included. Four weekly doses of rituximab 375 mg/m2 were administered. All patients had undergone splenectomy before rituximab administration. Accessory spleen was detected in 5 of 15 patients (33.3%). Median age at diagnosis was significantly higher in patients with accessory spleen than those without accessory spleen (40 (range 25–68 years) and 26 (range 7–40 years), respectively; p = 0.049). There was a trend for older age at time of rituximab initiation in patients with accessory spleen compared to the other group (median 51 (range 43–75 years) and 42.5 (range 30–60 years), respectively; p = 0.066). Median follow-up duration was 96 months (range 40–98). We demonstrated a significant correlation between accessory spleen presence and older age. Accessory spleen presence correlated with higher platelet and WBC counts. We showed good inverse correlation between presence of accessory spleen and time to early response (ER) to rituximab while the rate of early response (ER), late response (LR), sustained response (SR) and overall response (OR) did not differ with respect to the presence of acessory spleen.

HMGB1 is increased in patients with immune thrombocytopenia and negatively associates with Tregs

IntroductionRefractory or recurrent immune thrombocytopenia (ITP) patients suffer from the dual threat of high mortality and drug toxicity in addition to a very poor quality of life. Previous studies have shown that high mobility group box 1 (HMGB1) can promote the development of rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases. However, there is still a lack of research on the role of HMGB1 in the pathogenesis of ITP and whether it can be used as a predictor of efficacy and prognosis. Methods20 patients of adult ITP with splenectomy were chosen as the experimental group, while 19 adults underwent splenectomy for traumatic splenic rupture without other diseases as the control group. We measured the expression of HMGB1, RORγt and Foxp3 in spleen tissues by immunohistochemistry. Another 50 patients, of which 20 were newly diagnosed without treatment and 30 were refractory ITP, and 25 healthy controls were enrolled to analyse the expression levels and mRNA levels of HMGB1, RORγt and Foxp3 in peripheral blood by Western blot and RT-qPCR. The expression of HMGB1, IL-17 and IL-10 in serum was assayed by ELISA. PBMCs from newly diagnosed ITP patients were cultured in vitro which stimulated with recombinant humanHMGB1 (rHMGB1) and its inhibitors, in which the expressions of RORγt and Foxp3 were measured. ResultsThe expression of HMGB1 in the spleen with refractory ITP was significantly higher, while Foxp3 was decreased. A significant negative correlation was found between HMGB1 and Foxp3, and the overexpression of HMGB1 was significantly correlated with poor efficacy after splenectomy. The expression of HMGB1 and IL-17 increased and showed a positive correlation in serum, while IL-10 decreased and was negatively correlated with HMGB1. In PBMCs, the expression of HMGB1 and RORγt increased, while Foxp3 decreased, and the differences were more obvious in the refractory chronic ITP group. In a coculture system with PBMCs of untreated ITP patients, rHMGB1 increased RORγt expression and decreased Foxp3 expression, while an antiHMGB1 antibody partially corrected the above changes. ConclusionOur results suggest that HMGB1 is associated with the imbalance of Treg/Th17 cells and is involved in the pathogenesis of ITP.

The role of thrombopoietin receptor agonists in the management of adult primary immune thrombocytopenia: A single centre experience

Background/Aim. The availability of thrombopoietin receptor agonists (TPO-RA) for treating primary immune thrombocytopenia (ITP) has transformed its management over the last decade. The aim of this study was to assess the efficacy of TPO-RA in adults with chronic ITP treated at the University Clinical Center of Serbia. Methods. A total of 28 adult ITP patients ( 10 m ales and 18 females), who were given eltrombopag and/or romiplostim, were enrolled in the study. Data on demographic characteristics, ITP duration, previous therapeutic modalities, comorbidities, concomitant therapy both for comorbidities and ITP, indications for TPO-RA, bleeding episodes before and during TPO-RA, TPO-RA doses, adverse events, and response rates were collected from the patients? medical records. TPO-RAs were administered in patients with chronic refractory ITP when splenectomy was contraindicated/unfeasible and as preparation for splenectomy. Favorable treatment response was defined as a stable platelet count ? 50 ? 109/L. Results. A total of 22 (78.57%) and 14 (50.0%) patients were treated with eltrombopag and romiplostim, respectively. A good treatment response (GTR) was achieved in 81.8% of the patients receiving eltrombopag and 71.4% of those treated with romiplostim. The non-responders to eltrombopag (4 patients) and those who had lost their response to eltrombopag (4 patients) were switched to romiplostim. Six of 8 patients achieved a GTR. At the time of TPO-RA initiation, 46.4% of the patients used concomitant ITP therapy, which was ceased in all those with a GTR. The following adverse effects of TPO-RA were registered: transaminitis and transient ischemic attack for eltrombopag ? one patient each, and pulmonary embolism in one romiplostim-treated patient. Conclusion. Our study showed that TPO-RAs are an effective and safe treatment option since the majority of patients achieved stable remission without bleeding episodes.

THE USE OF ROMIPLOSTIM IN AN INFANT

Immune thrombocytopenia (ITP) is the most common platelet disorder in children, peaking between the ages of 1-7.The first line therapy consists of intravenous immunoglobulin, anti-D immunoglobulin or corticosteroids. Second-line treatment options are immunosuppressive therapy, Rituximab.Thrombopoietin receptor agonists are used, which increase platelet production in the bone marrow. Our case report on a child with refractory chronic ITP, who failed the first and second line therapy.

A multicenter retrospective analysis on therapeutic plasma exchange in immune thrombocytopenic purpura

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia and skin and mucosal bleeding. In patients with an indication for treatment, corticosteroids, intravenous immunoglobulin (IVIg) and anti-D are recommended as the first line, while splenectomy, thrombopoietin receptor agonists or rituximab are recommended second line options. Approximately 10 % of adult patients with ITP fall into the chronic refractory ITP group. Therapeutic plasma exchange (TPE) has generally been tested in patients with refractory ITP, who have failed to respond to conventional treatments, in case of bleeding or prior to surgical interventions. It has been stated that elimination of the antibodies that are held responsible in the pathogenesis of the disease has an effective role in the treatment. In this article, we present the results of 17 patients, who underwent TPE for refractory ITP, together with the literature data.

Mesenchymal Stem Cells Improve Platelet Counts in Mice with ITP

INTRODUCTION: Patients with chronic refractory immune thrombocytopenia (ITP) have the high risk of death and complications, which urge us to seek for new treatment alternatives. Currently, bone marrow-derived mesenchymal stem cells (BMSCs) have been extensively utilized for autoimmune diseases. However, it is still lack of evidence in vivo about the therapeutic benefits and the possible underlying mechanisms of BMSCs in ITP, which is also known as an acquired autoimmune disease. In this study, we transplanted BMSCs into a passive ITP mouse model to explore the therapeutic effects and immunosuppressive mechanisms of BMSCs in ITP disease.METHODS: The passive ITP mouse model was induced by dose-escalation injection of monoclonal antibody MWReg30. Mice were randomly divided into two groups: experimental group (2-4×106 BMSCs were injected into each ITP mouse through the tail vein on Day 3) and control group (ITP mice). PLT counts were enumerated by an automatic blood cell counter. The serum levels of cytokines (IL-10 and TGF-β1) were examined by ELISAs and the frequency of Treg cells by flow cytometry. The statistical analysis was processed by SPSS software version 19.0.RESULTS: We successfully induced a passive ITP mouse model with very low levels of PLT counts for 8 days (PLT counts were reduced to half of the initial values by 24 hours and were relatively constant throughout the study). The PLT counts in experimental group on Day 4 to Day 8 were (263±17)×109/L, (482±35)×109/L, (367±38)×109/L, (385±107)×109/L, and (317±48)×109/L, which were significantly higher than those in control group [ (159±19)×109/L, (238±20)×109/L, (175±32))×109/L, (129±7)×109/L, and (170±16)×109/L, respectively ]. The levels of serum TGF-β1 and IL-10 were significantly higher in experimental group compared with the control group [ (116.61±12.59)pg/ml and (348.89±44.49)pg/ml vs. (72.78±15.70) pg/ml and (134.61±27.59)pg/ml; p <0.05]. The ratios of Treg cells both in splenocytes and peripheral blood were significantly higher after transplantation of BMSCs [ (15.79±0.55)% and (6.37±0.45)% vs. (10.25±0.55)% and (4.80±0.26)%; p<0.05].CONCLUSIONS: BMSCs transplantation is an effective treatment for ITP in mice. The key mechanisms underlying the positive therapeutic impact may due to the BMSCs secreting suppressive cytokines TGF-β1 and IL-10 and increasing the proportion of Treg cells, which play key roles in both the maintenance of immune tolerance and the inactivation of macrophage. DisclosuresNo relevant conflicts of interest to declare.

Chronic Refractory Immune Thrombocytopenia Is Associated With Variants in Immune Genes.

The pathogenesis of chronic refractory immune thrombocytopenia (C/RITP) is mechanistically complex and considerably varies across patients. Few studies have focused on the genetic characteristics of C/RITP in children. The aim of this study was to analyze and summarize the clinical manifestations and genetic characteristics of C/RITP children with mutations in immune-related genes. In the study, 51 children with variants in immune-related genes (mutation group) and 103 children with no abnormal mutations (control group) were enrolled. Children in the mutation group showed severity of hemorrhage, a higher incidence of abnormal immunological indices, and an increased expression of SLE biomarkers. The number of peripheral T and B lymphocytes in the mutation group significantly increased. Nine patients (17.6%) had probable pathogenic variant genes associated with primary immunodeficiencies (TNFRSF13B, CARD11, CBL, and RAG2), and 42 patients (82.4%) had variants of uncertain significance in 23 genes. C/RITP patients with variants in immune-related genes had more severe bleeding, abnormal immunological indices, and an increased expression of SLE biomarker. Next-generation sequenciong (NGS) might be a useful way to differentiate those patients from C/RITP.

Thrombopoietin receptor agonists for pediatric refractory chronic immune thrombocytopenia

Various treatments have been used to treat chronic immune thrombocytopenic purpura in children; however, none of it has been established as the standard of care. The administration of thrombopoietin receptor agonists (TPO-RAs) has been approved as a new treatment option in Japan. In this case series, TPO-RAs were administered to 16 patients (eltrombopag, n=9; romiplostim, n=7). Excluding the data of two patients who underwent splenectomy immediately after starting treatment with these medicines, platelet counts increased to ≥50,000/µl in seven patients. The adverse events recorded were grade 2 liver dysfunction (n=1), according to the common terminology criteria for adverse events version 4, and myelofibrosis (classified as MF1 or mild reticulin fibrosis), as observed on bone marrow biopsy (n=2). We continued the administration of TPO-RAs at the same dose in these patients because the complications they experienced were mild. The risk of adverse events associated with long-term use of TPO-RAs in this pediatric population remains unclear, and a prospective evaluation is needed.

Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study

AbstractManagement of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA–related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.

COVID‐19 presenting with autoimmune hemolytic anemia in the setting of underlying immune dysregulation

To the Editor: The 2019 novel coronavirus (COVID-19 due to SARS-CoV-2 infection) pandemic has been declared an international public health emergency associated with substantial mortality with global case numbers surpassing 3 000 000.1 The clinical spectrum of COVID-19 disease in children and young adults ranges from asymptomatic infections to mild symptoms, only rarely leading to fulminant respiratory failure.2 Here, we report the first case of life-threatening immune cytopenias in a patient with SARS-CoV-2 infection. This case highlights a previously unreported potential COVID-19-related complication.2, 3 A17-year-old male with a history of refractory chronic immune thrombocytopenia (cITP) presented with progressive jaundice and fatigue in the setting of 4 days of emesis, diarrhea, and fevers. Prior to this presentation, the patient's cITP had been well controlled on eltrombopag and mycophenolate. Given the history of immune cytopenia, lymphopenia, splenomegaly, hypogammaglobulinemia, and a persistently elevated CD3+CD4-CD8-T-cell population in peripheral blood, the patient had been thought to have autoimmune lymphoproliferative syndrome (ALPS) or an alternative immune dysregulation syndrome. Clinical sequencing had been unrevealing to date for a known genetic cause of immune dysregulation.4 Importantly, the patient had previously negative direct antiglobulin (DAT) testing without signs of anemia or hemolysis, including in the months prior to presentation. Upon presentation, the patient was noted to be alert but fatigued. He was febrile, tachycardic, tachypneic, and hypoxic. His initial exam was notable for marked pallor and jaundice. He had clear breath sounds bilaterally, but increased work of breathing. Chest radiograph showed mild prominence of perihilar markings. PCR nasopharyngeal swab testing for SARS-CoV-2 was positive and negative for other respiratory viruses. Laboratory evaluation demonstrated warm DAT positive (IgG 3+, C3 1+) reticulocytopenic anemia with a hemoglobin of 2.5 g/dL and absolute reticulocyte count of 0.011 cells/μL, LDH of 1280 units/L, and total bilirubin of 8.9 mg/dL. Other abnormal hematological parameters included lymphopeniaand thrombocytopenia (Figure 1A). A peripheral blood smear demonstrated rouleaux formation, presence of microspherocytes, hypochromic microcytic red blood cells, and large platelets (Figure 1B). The patient was admitted and treated with intravenous corticosteroids and oxygen supplementation and received a red blood cell transfusion. Within 48 h after initiation of corticosteroids, hemolysis improved with a stabilized hemoglobin and significant decrease in bilirubin and LDH. Additionally, oxygen saturations normalized after red blood cell transfusion and his respiratory status improved. Given the patient's history of refractory cITP, he was restarted on his prior regimen of eltrombopag and mycophenolate and a steroid wean was initiated. Overall, this presentation was consistent with Evans syndrome with warm autoimmune hemolytic anemia (AIHA), a disease that can be triggered through polyclonal activation of autoreactive B-lymphocytes, leading to the emergence of red blood cell directed autoantibodies.5 While a direct causal relationship between SARS-CoV-2 infection and manifestation of AIHA cannot be demonstrated, the temporal association of this presentation suggests SARS-CoV-2 infection as a potential trigger, particularly in a patient with an underlying immune dysregulation syndrome. With the ongoing pandemic of COVID-19 disease attributable to SARS-CoV-2 infection, we suggest that patients who are immunosuppressed or have underlying immune dysregulation may have atypical presentations. Indeed, the notable immune activation with COVID-19 disease in adults3 may be associated with altered presentations in those with immune dysregulation, such as the development of new onset autoantibodies as we report here. National Institutes of Health; Grant Number: R01 DK103794.

Long-term sustained response to fostamatinib in two patients with chronic refractory immune thrombocytopenia (ITP).

Care of patients with chronic immune thrombocytopenia (ITP) who are refractory to available treatments can be quite challenging. Fostamatinib, an oral Syk inhibitor, is the newest FDA-approved agent for ITP. Phase 3 clinical trials demonstrated an overall response in 43% of patients treated with fostamatinib and use for twoyears has been reported. Herein, we report two patients with long histories of ITP without lasting responses to numerous first-, second- and third-line therapies with prolonged responses to ongoing fostamatinib. This shows that patients unresponsive to other agents may respond to fostamatinib and can have sustained benefit.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective:The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP).Materials and Methods:A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed.Results:The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%).Conclusion:Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

A multi-centric study on the efficacy of eltrombopag in management of refractory chronic immune thrombocytopenia

The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Primary immune thrombocytopenia (ITP) treated with romiplostim in routine clinical practice: retrospective study from the United Kingdom ITP Registry.

BackgroundRomiplostim is a thrombopoietin‐mimetic peptibody for adult refractory chronic immune thrombocytopenia (ITP). We aimed to describe ITP patients receiving romiplostim, platelet counts and romiplostim usage in UK clinical practice.MethodsThis was a retrospective cohort study of patients in the UKITP Registry who received romiplostim between October 2009 and January 2015, including data up to 6 months before romiplostim initiation through follow‐up.ResultsOf 1440 patients in the UKITP Registry, 118 adults with primary ITP were eligible. Before romiplostim, 22% had splenectomy, 12% received platelet transfusion, 97% received ≥ 1 different ITP medication and 77% received ≥ 3. Most patients (73%) initiated romiplostim ≥ 1 year after ITP diagnosis (chronic phase). The mean duration of romiplostim treatment was 5.7 (SE 0.9) months, and the median was 1.4 months (IQR: 0.2, 6.5). Mean platelet count before romiplostim was 38 × 109/L, rising to 103 × 109/L within 1 month, and remaining 50‐150 × 109/L through up to 3 years of follow‐up. After romiplostim, 4% of patients had splenectomy, 6% received platelet transfusion, and 57% received just one ITP medication other than romiplostim.ConclusionThe study provides valuable insights into the real‐world use of romiplostim in primary ITP in routine practice and highlighted the timing of romiplostim initiation at different ITP disease phases.

Expression of HMGB1 in Spleen of Adult Patients with Chronic and Refractory Immune Thrombocytopenia and Its Significance

To investigate the expression and clinical significance of high mobility group box 1(HMGB1) in spleen of adult patients with chronic and refractory immune thrombocytopenia(ITP). Twenty chronic and refactory ITP patients received splenectomy were enrolled in ITP group and 20 cases of traumatic spleen rupture were enrolled in control group. The splenectomy efficacy in ITP patients was analyzed retrospectively. The HMGB1 expression in spleen tissue was detected by immunohistochemistry, and the correlation between different expression levels of HMGB1 and splenectomy efficacy were analysed. Meanwhile, the protein expression levels of HMGB1 in peripheral blood serum and mononuclear cells(PBMNC) of 25 patients with chronic and refractory ITP were detected by ELISA and Western blot. The median platelet count before splenectomy was 7.5 (0-20) ×109/L; all the patients showed that the initial response to splenectomy within the first month after operation was 100%, the median time of response was 1 day (1-6 days). The median peak platelet count post splenectomy was 448.5 (161-1272)×109/L. In the median time of 10(3-30) months, the platelets count in 8 patients was reduced to varying degrees. After a median follow-up of 69.5 months (22-195), complete response was found in 12 patients, 4 cases showed response and 4 did not. The HMGB1 expression positive rate in spleen of ITP patients was significantly higher than that in control group (85.0% vs 15.0%)(P<0.001). There were a negative correlation between the HMGB1 expression in ITP and therapeutic outcome after splenectomy (r=-0.791, P<0.01). In addition, HMGB1 expression levels in serum and PBMNC of the patients with chronic refractory ITP were also significantly higher than that in healthy controls (P<0.01). The splenectomy has been found to be effective therapeutic method for patients with ITP, the HMGB1 highly express in the spleen of the patients with chronic refractory ITP, but negatively correlats with the therapeutic outcome after splenectomy.