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Immune thrombocytopenia (ITP) is a hematologic disorder characterized by a low platelet count, leading to an increased risk of bleeding. This review provides an overview of the historical milestones, pathophysiology, and treatment advances in ITP. Historical perspectives trace back to Avicenna’s description in the eleventh century to pivotal Harrington-Hollingsworth experiment in 1950, laid the groundwork for understanding the immune-mediated platelet destruction intrinsic to ITP. Subsequent developments in investigation techniques, such as platelet-survival studies and antibody assays, contributed to diagnostic advancements. Treatment modalities have evolved signifcantly from the traditional approach of splenectomy to the use of corticosteroids, immunosuppressants, and novel targeted therapies. The efcacy and safety profles of these treatments have been refned through clinical trials and consensus guidelines. Ongoing research continues to unravel the genetic and molecular underpinnings of ITP, ofering insights into disease mechanisms and potential therapeutic targets. Emerging therapies, including immunomodulatory agents, hold promise for improving outcomes and quality of life for patients with ITP. In conclusion, this review provides a synthesis of historical insights, pathophysiological mechanisms, and treatment strategies in ITP. By elucidating the complex interplay between immune dysregulation and platelet destruction, this knowledge serves as a foundation for advancing the diagnosis, management, and future therapeutic innovations in ITP.

Summary: There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single‐centre, prospective, observational study. The eltrombopag dosage was adjusted, and children were divided into three groups: the maintenance, discontinuation, and increase groups. Concentration and other data were compared to explore concentration value in guiding the individualized treatment of paediatric ITP. Thirty‐nine patients were enrolled, including 23 in the maintenance group, 3 in the discontinued group and 13 in the increase group. 3 patients discontinued eltrombopag due to ADRs, which was significantly higher than patients in the maintenance group (t = 3.606, p = 0.001). In all, 13 patients increased their dosage due to poor response, whose concentration and platelet count were significantly lower than patients in the maintenance group (t = 2.461, p = 0.019; t = 4.633, p < 0.001). Two months after the increase, the number of patients reaching CR and R respectively increased by 2 and 3, while the median platelet count was significantly raised (Z = −2.411, p = 0.016). Concentration could be used as a reference index for the individualized treatment of eltrombopag in paediatric ITP. [ABSTRACT FROM AUTHOR]

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food‐drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single‐dose, 2‐period crossover design was employed, involving fasting and fed conditions with a 10‐day washout period. Ninety‐six healthy volunteers received a single oral dose of 25 mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high‐fat, low‐calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography‐tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration‐time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration‐time curve from time 0 to the last measurable concentration, and area under the concentration‐time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%‐125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high‐fat, low‐calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations. [ABSTRACT FROM AUTHOR]

This study aims to determine the bioequivalence of the reference preparation and the test preparation containing eltrombopag when both were given during the COVID-19 pandemic while fasting. Participants in the research were healthy male Caucasian subjects. One film-coated tablet of the test preparation or one film tablet of the reference preparation, equivalent to 75 mg of eltrombopag, was given to the participants in a randomized order throughout each treatment session. At pre determined blood sampling points, blood samples were taken to determine the pharmacokinetics of eltrombopag. Eltrombopag concentrations in the samples were determined using an LC-MS/MS technique verified using ESI(−). The study results were used to calculate the rate (the maximum plasma concentration, or Cmax) and extent (area under the concentration-time curve of plasma, or AUC(0−72) and AUC(0−t) of eltrombopag absorption from the test preparation and reference preparation. The 90% confidence intervals (CI) of the ln-transformed AUC(0−72), AUC(0−t), and Cmax of eltrombopag met the bioequivalence requirements of 80.00–125.00%. Both trial preparations had a similar and very satisfactory safety profile. Key points: • Bioequivalence of eltrombopag film-coated tablets • Safety evaluation of eltrombopag film-coated tablets [ABSTRACT FROM AUTHOR]

Summary Due to the limited real‐world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty‐two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO‐RAs), resulting in an 88% platelet response rate. Sixty‐three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO‐RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long‐term financial burden of AVA. [ABSTRACT FROM AUTHOR]

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59–88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, trastuzumab and pertuzumab have been used in treatment protocols for patients with HER2-positive colorectal cancer. Although severe thrombocytopenia is an uncommon side effect of anti-HER2 antibody therapy, we present the first patient with HER2-positive metastatic rectal cancer who developed significant thrombocytopenia after trastuzumab and pertuzumab administration. Case Presentation: The condition was identified as drug-induced immune thrombocytopenia associated with trastuzumab and pertuzumab. Despite the discontinuation of anti-HER2 treatment and administration of corticosteroids, and in addition to frequent platelet transfusions, a low platelet count persisted. Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Subsequently, the patient’s platelet count did not decrease further but rather improved. Conclusion: Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential. [ABSTRACT FROM AUTHOR]

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients. [ABSTRACT FROM AUTHOR]

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia

Introduction: In recent years, trastuzumab and pertuzumab have been used in treatment protocols for patients with HER2-positive colorectal cancer. Although severe thrombocytopenia is an uncommon side effect of anti-HER2 antibody therapy, we present the first patient with HER2-positive metastatic rectal cancer who developed significant thrombocytopenia after trastuzumab and pertuzumab administration. Case Presentation: The condition was identified as drug-induced immune thrombocytopenia associated with trastuzumab and pertuzumab. Despite the discontinuation of anti-HER2 treatment and administration of corticosteroids, and in addition to frequent platelet transfusions, a low platelet count persisted. Consequently, we determined that the patient presented with a condition similar to immune thrombocytopenic purpura (ITP) and selected a treatment approach consisting of eltrombopag, a thrombopoietin receptor agonist. Subsequently, the patient’s platelet count did not decrease further but rather improved. Conclusion: Although uncommon, anti-HER2 antibodies can cause severe thrombocytopenia. Furthermore, if thrombocytopenia persists after treatment discontinuation and the administration of corticosteroids, exploring treatment options aligned with managing ITP is essential.

Introduction. As a result of portal hypertension (sequestration of platelets in an enlarged spleen) and liver failure (decreased production of thrombopoietin in the liver) in liver cirrhosis, thrombocytopenia develops, which is associated with the risk of periprocedural/perioperative bleeding complications. There are still unresolved questions regarding risk stratification of bleeding complications, the prognostic role of thrombocytopenia, as well as the need for treatment of thrombocytopenia and its methods.Materials and methods. The Russian Scientific Liver Society selected a panel of experts in the field of therapeutic and surgical hepatology, hematology, transfusion medicine to make reasoned statements and recommendations on the issue of treatment of thrombocytopenia before elective surgery / invasive procedures in patients with liver cirrhosis.Results. Relevant clinical issues were determined based on the PICO principle (patient or population, intervention, comparison, outcome). The Delphi panel made five questions and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the results of search and critical analysis of medical literature using keywords in English- and Russian-language databases. The formulated questions could be combined into four categories: bleeding risk stratification, the prognostic value of thrombocytopenia, the necessity and methods of thrombocytopenia drug correction, and bleeding risk reduction.Conclusions. The results of experts' work are directly related to high-quality management of patients with liver cirrhosis and thrombocytopenia, who have scheduled invasive procedures/surgery. Thus, this recommendations and statements can be used in clinical practice.

Introduction: This study aimed to evaluate the results obtained with the preference of eltrombopag according to the line of treatment in patients diagnosed with ITP. Methods: This retrospective study included 51 patients who were treated with eltrombopag for chronic ITP at 3 different centers. Diagnosis of ITP was based on the current literature. Results: Thirty patients (58.8%) received eltrombopag as second-line treatment, 16 patients (31.4%) as third-line, 3 patients (5.9%) as fourth-line treatment, and 2 patients (3.9%) as fifth-line treatment. Twenty-four out of 30 patients (80%) who received eltrombopag as second-line therapy and 12 out of 16 patients who received eltrombopag as third-line therapy demonstrated durable response with no further treatment requirements. Eltrombopag treatment in the second or third line did not affect treatment outcomes (p=0.72). Conclusion: Eltrombopag in the second or third line of treatment did not have a significant effect on treatment response. The earlier line choice of eltrombopag, duration, and possibility of sustained response should be taken into consideration. The lack of a significant relationship between the line of treatment and response to eltrombopag as a TPO-RA should be considered encouraging in terms of long-term follow-up.

Introduction Enfortumab vedotin is an antibody‐drug conjugate targeting Nectin‐4 for the treatment of advanced urothelial carcinoma in patients previously treated with platinum‐containing chemotherapy and immune checkpoint inhibitors. Common adverse events include rashes, peripheral neuropathy, and hyperglycemia. However, there are no reports on the development of myelodysplastic syndrome during enfortumab vedotin therapy in clinical settings. Case presentation A 72‐year‐old male patient experienced prolonged and severe thrombocytopenia 18 weeks after the start of enfortumab vedotin therapy for metastatic urothelial carcinoma, requiring daily platelet transfusions. Bone marrow examination and chromosomal analysis confirmed the diagnosis of myelodysplastic syndrome. Treatment with eltrombopag proved to be effective. Conclusion This is the first report of the development of myelodysplastic syndrome during enfortumab vedotin therapy in a clinical setting. Although rare, myelodysplastic syndrome can occur during enfortumab vedotin therapy.

Immune Thrombocytopenic Purpura (ITP), an autoimmune disease, is characterised by isolated thrombocytopenia, with or without bleeding. Thyroid autoimmune illness can coexist with ITP. The specific clinical characteristics are still unknown. The length of ITP or the patients’ response to treatment is not related to their thyroid condition. In patients with ITP, thyroid impairment is more common. In the present case report, a 60-year-old female patient, a known case of asthma, presented to the hospital with complaints of swelling in the neck along with transient episodes of breathlessness for 3-4 years. On local examination, a butterfly-shaped mass was seen in the neck, which moved upwards on deglutination but did not move on protrusion of the tongue. Pemberton’s sign was also positive. On palpation, the thyroid measured around 8×6 cm in size, thyroid lobes were bosselated, consistency was firm, and no bruit was heard on auscultation. Based on routine laboratory findings, she was found to have refractory thrombocytopenia with a normal thyroid profile. Further investigations revealed that the patient had positive antithyroid stimulating hormone antibodies, and Fine Needle Aspiration Cytology (FNAC) showed colloid nodular goitre with haemorrhagic cystic changes. A bone marrow biopsy was performed in view of refractory thrombocytopenia, which was suggestive of ITP. The patient was advised to take tablet eltrombopag, after which the platelet counts improved drastically. Subsequently, the patient was advised to undergo thyroidectomy, but this could not be done due to haemodynamic instability.

Introduction: Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Methods: Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023.Results: Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. Conclusion: The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. [ABSTRACT FROM AUTHOR]

Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty‐three AA children with an average age of 7.9 (range of 3.0‐14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty‐three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele‐T carrier of adenosine triphosphate‐binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild‐type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight‐adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the results obtained with the preference of eltrombopag according to the line of treatment in patients diagnosed with ITP. Methods: This retrospective study included 51 patients who were treated with eltrombopag for chronic ITP at 3 different centers. Diagnosis of ITP was based on the current literature. Results: Thirty patients (58.8%) received eltrombopag as second-line treatment, 16 patients (31.4%) as third-line, 3 patients (5.9%) as fourth-line treatment, and 2 patients (3.9%) as fifth-line treatment. Twenty-four out of 30 patients (80%) who received eltrombopag as second-line therapy and 12 out of 16 patients who received eltrombopag as third-line therapy demonstrated durable response with no further treatment requirements. Eltrombopag treatment in the second or third line did not affect treatment outcomes (p=0.72). Conclusion: Eltrombopag in the second or third line of treatment did not have a significant effect on treatment response. The earlier line choice of eltrombopag, duration, and possibility of sustained response should be taken into consideration. The lack of a significant relationship between the line of treatment and response to eltrombopag as a TPO-RA should be considered encouraging in terms of long-term follow-up. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy. [ABSTRACT FROM AUTHOR]

Immune Thrombocytopenic Purpura (ITP), an autoimmune disease, is characterised by isolated thrombocytopenia, with or without bleeding. Thyroid autoimmune illness can coexist with ITP. The specific clinical characteristics are still unknown. The length of ITP or the patients’ response to treatment is not related to their thyroid condition. In patients with ITP, thyroid impairment is more common. In the present case report, a 60-year-old female patient, a known case of asthma, presented to the hospital with complaints of swelling in the neck along with transient episodes of breathlessness for 3-4 years. On local examination, a butterfly-shaped mass was seen in the neck, which moved upwards on deglutination but did not move on protrusion of the tongue. Pemberton’s sign was also positive. On palpation, the thyroid measured around 8×6 cm in size, thyroid lobes were bosselated, consistency was firm, and no bruit was heard on auscultation. Based on routine laboratory findings, she was found to have refractory thrombocytopenia with a normal thyroid profile. Further investigations revealed that the patient had positive antithyroid stimulating hormone antibodies, and Fine Needle Aspiration Cytology (FNAC) showed colloid nodular goitre with haemorrhagic cystic changes. A bone marrow biopsy was performed in view of refractory thrombocytopenia, which was suggestive of ITP. The patient was advised to take tablet eltrombopag, after which the platelet counts improved drastically. Subsequently, the patient was advised to undergo thyroidectomy, but this could not be done due to haemodynamic instability. [ABSTRACT FROM AUTHOR]

While studies have explored the feasibility of switching between various thrombopoietin receptor agonists in treating immune thrombocytopenia (ITP), data on the switching from eltrombopag to hetrombopag remains scarce. This post-hoc analysis of a phase III hetrombopag trial aimed to assess the outcomes of ITP patients who switched from eltrombopag to hetrombopag. In the original phase III trial, patients initially randomized to the placebo group were switched to eltrombopag. Those who completed this 14-week eltrombopag were eligible to switch to a 24-week hetrombopag. Treatment response, defined as a platelet count of ≥ 50 × 109/L, and safety were evaluated before and after the switch. Sixty-three patients who completed the 14-week eltrombopag and switched to hetrombopag were included in this post-hoc analysis. Response rates before and after the switch were 66.7% and 88.9%, respectively. Among those with pre-switching platelet counts below 30 × 109/L, eight out of 12 patients (66.7%) responded, while eight out of nine patients (88.9%) with pre-switching platelet counts between 30 × 109/L and 50 × 109/L responded post-switching. Treatment-related adverse events were observed in 50.8% of patients during eltrombopag treatment and 38.1% during hetrombopag treatment. No severe adverse events were noted during hetrombopag treatment. Switching from eltrombopag to hetrombopag in ITP management appears to be effective and well-tolerated. Notably, hetrombopag yielded high response rates, even among patients who had previously shown limited response to eltrombopag. However, these observations need to be confirmed in future trials. [ABSTRACT FROM AUTHOR]

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015–2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids (p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase. [ABSTRACT FROM AUTHOR]

Summary: Few studies have reported the real‐world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO‐RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO‐RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO‐RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment‐free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO‐RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO‐RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO‐RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO‐RAs had similar efficacy and safety profiles to those reported in clinical studies. [ABSTRACT FROM AUTHOR]

Cytopenia is a common side effect after chimeric antigen receptor T cell (CAR-T) therapy but is unusual at late timepoints when it is most commonly due to bone marrow (BM) failure, myelodysplasia (MDS) or other secondary malignancies. In this case report, we describe a patient who developed severe aplastic anaemia 18 months after CD19 CAR-T therapy, and shortly after COVID-19 vaccination. This is the first description of severe aplastic anaemia triggered by COVID-19 vaccination as a cause of post-CAR-T cytopenia. The patient described was treated with a combination of eltrombopag and ciclosporin due to frailty and had a rapid and complete clinical response to this therapy, providing an effective option for the treatment of immune-related cytopenia post-CAR-T in an increasingly elderly and frail population.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and decreased platelet production. The formation of antibodies to platelet and megakaryocyte glycoproteins plays a major role in the pathophysiology of ITP. All treatment strategies for ITP attempt to increase platelet count and reduce the risk of bleeding complications. Corticosteroids remain the most commonly used first-line therapy for ITP, but their long-term use is limited due to the development of severe complications. Today the new treatment methods including the use of thrombopoietin receptor agonists (TPO-RA) romiplostim, eltrombopag and avatrombopag with a number of advantages over standard therapy are of great interest. These drugs are recommended for use in the second-line therapy and show high efficacy in patients with ITP, particularly in real clinical practice. In most cases TPO-RA provide stable and long-term remission of the disease, allowing you to reduce or discontinue the use of glucocorticosteroids and avoid splenectomy. Many studies of the mechanism of action, efficacy and toxicity of TPO-RA have been performed. the research results significantly expand our knowledge about these agents. This review provides comparative data of the TPO-RA safety and the main aspects of their clinical use. The features of the new drug avatrombopag, recently approved for use in the Russian federation, are described. the overview presents the advantages and limitations of each drug, possible adverse events and methods for their control.

ABSTRACT Importance Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported. Objective This study aims to explore the appropriate eltrombopag concentration in pediatric ITP. Methods This was a single‐center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×109/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high‐performance liquid chromatography‐mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics‐concentration, concentration‐response, and concentration‐ADRs were analyzed. Results A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response. Interpretation Eltrombopag proves efficacious and well‐tolerated for treating pediatric ITP. However, prolonged and high‐dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.

Acquired Aplastic Anemia (AAA) is a rare disease involving primary bone marrow failure with consequent pancytopenia. The addition of the synthetic thrombopoietin-receptor agonist eltrombopag (ELT) to standard immunosuppression for the treatment of AAA has led to improvements in hemopoietic outcomes of AAA. Most of the data on the use of ELT for AAA was based on a maximum of 6 months of therapy. However, in clinical practice, a longer use of ELT is often required. This paper presents a monocentric real-life experience with prolonged use of ELT in 10 patients with AAA, showing data on effectiveness and safety. In our cohort, a high rate of response to ELT added to standard immunosuppression in patients with varying grades of severity of AAA was reported. After a median (range) observation time of 47.5 (31–75) months, the treatment with ELT was feasible with an overall response probability of 70% and was not associated with any concerning adverse event. Two episodes of relapse were reported; no signs of evolution have been reported so far. In conclusion, ELT as a dose-response-adjusted prolonged therapy associated with standard immunosuppression in AAA patients not eligible for transplant seems to be feasible to consolidate and maintain the response.

The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed to evaluate the stability of the ligand across specific proteins, showing favorable characteristics. For the first time, we examined the presence of TPO-R in human umbilical cord mesenchymal stem cells (hUCMSC) and human gingival mesenchymal stem cells (hGMSC) proliferation. Furthermore, treatment with EPAG demonstrated angiogenesis and vasculature formation of endothelial lineage derived from both MSCs. It also indicated the activation of critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, and FLI-1. Additional experiments confirmed that EPAG could be an ideal molecule for protecting against UVB radiation damage, as gene expression (JAK-2, ERK-2, MCL-1, NFkB, and STAT-3) and protein CD90/cMPL analysis showed TPO-R activation in both hUCMSC and hGMSC. Overall, EPAG exhibits significant potential in treating radiation damage and mitigating the side effects of radiotherapy, warranting further clinical exploration.

ABSTRACTObjective This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.Methods PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.Results This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54–3.12; P

Hematopoietic stem and progenitor cells (HSPCs) continuously generate platelets throughout one's life. Inherited Platelet Disorders affect ≈ 3 million individuals worldwide and are characterized by defects in platelet formation or function. A critical challenge in the identification of these diseases lies in the absence of models that facilitate the study of hematopoiesis ex vivo. Here, a silk fibroin‐based bioink is developed and designed for 3D bioprinting. This bioink replicates a soft and biomimetic environment, enabling the controlled differentiation of HSPCs into platelets. The formulation consisting of silk fibroin, gelatin, and alginate is fine‐tuned to obtain a viscoelastic, shear‐thinning, thixotropic bioink with the remarkable ability to rapidly recover after bioprinting and provide structural integrity and mechanical stability over long‐term culture. Optical transparency allowed for high‐resolution imaging of platelet generation, while the incorporation of enzymatic sensors allowed quantitative analysis of glycolytic metabolism during differentiation that is represented through measurable color changes. Bioprinting patient samples revealed a decrease in metabolic activity and platelet production in Inherited Platelet Disorders. These discoveries are instrumental in establishing reference ranges for classification and automating the assessment of treatment responses. This model has far‐reaching implications for application in the research of blood‐related diseases, prioritizing drug development strategies, and tailoring personalized therapies. [ABSTRACT FROM AUTHOR]

Summary: Diamond–Blackfan anaemia (DBA) is a rare, inherited bone marrow failure syndrome with a ribosomal defect causing slowed globin chain production with normal haem synthesis, causing an overabundance of reactive iron/haem and erythroid‐specific cellular toxicity. Eltrombopag, a non‐peptide thrombopoietin receptor agonist, is a potent intracellular iron chelator and induced a robust durable response in an RPS19‐mutated DBA patient on another trial. We hypothesized eltrombopag would improve RBC production in DBA patients. We conducted a single‐centre, single‐arm pilot study (NCT04269889) assessing safety and erythroid response of 6 months of daily, fixed‐dose eltrombopag for DBA patients. Fifteen transfusion‐dependent (every 3–5 weeks) patients (median age 18 [range 2–56]) were treated. One responder had sustained haemoglobin improvement and >50% reduction in RBC transfusion frequency. Of note, 7/15 (41%) patients required dose reductions or sustained discontinuation of eltrombopag due to asymptomatic thrombocytosis. Despite the low response rate, eltrombopag has now improved erythropoiesis in several patients with DBA with a favourable safety profile. Dosing restrictions due to thrombocytosis may cause insufficient iron chelation to decrease haem production and improve anaemia in most patients. Future work will focus on erythropoiesis dynamics in patients and use of haem synthesis inhibitors without an impact on other haematopoietic lineages. [ABSTRACT FROM AUTHOR]

Objectives We aimed to investigate the safety and effectiveness of eltrombopag for adult patients with refractory immune thrombocytopenia (ITP) secondary to connective tissue disease (CTD). Methods This is a single-centre, retrospective cohort and propensity score-matched study. Data from CTD-ITP patients treated with eltrombopag between January 2019 and January 2023 were retrospectively analysed. Baseline characteristics and follow-up information were recorded. CTD patients without ITP were matched to identify the risk factors associated with CTD-ITP performed by Logistic regression analysis. Results Twenty patients were enrolled, including 5 systemic lupus erythematosus (SLE), 9 Sjögren's syndrome (SS) and 6 undifferentiated connective tissue disease (UCTD). Nineteen (95%) patients were female, and the median age was 59 years. Logistic regression analysis showed that anaemia (OR = 8.832, P  =   0.007) was associated with increased risk of ITP, while non-erosive arthritis (OR = 0.045, P  =   0.001) and interstitial lung disease (OR = 0.075, P  =   0.031) were associated with reduced risk. Fourteen patients (70%) achieved a complete response (CR) and one (5%) achieved a partial response (PR). The median response time was 14 days. The median platelet count was 8.5 × 109/l at baseline of eltrombopag and increased to 122 × 109/l after 4 weeks. No adverse events were observed. Conclusions Eltrombopag appears to be effective, safe and well-tolerated in refractory ITP patients with CTD; larger studies are needed to confirm the generalizability of these findings. [ABSTRACT FROM AUTHOR]

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50mg/d from +1 day until PLT >50 × 109/L or 1month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, themedian time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT\counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Simple Summary: Several recent studies have demonstrated encouraging results in treating patients with myelodysplastic syndromes/neoplasms (MDSs). This review focuses on the latest conceptual and therapeutic advances in the management of adults with MDS, addressing diagnostic principles, classification updates, and prognostic stratification systems, as well as improvements in clinical approaches that provide significant benefits through novel treatments, which may, in turn, represent a valuable basis for developing future clinical trials. Myelodysplastic syndromes/neoplasms (MDSs) encompass a range of hematopoietic malignancies, commonly affecting elderly individuals. Molecular alterations in the hematopoietic stem cell compartment drive disease pathogenesis. Recent advancements in genomic profiling have provided valuable insights into the biological underpinnings of MDSs and have expanded therapeutic options, particularly for specific molecularly defined subgroups. This review highlights the diagnostic principles, classification updates, prognostic stratification systems, and novel treatments, which could inform future clinical trials and enhance the management of adult MDS patients, particularly for specific molecularly defined subgroups. [ABSTRACT FROM AUTHOR]

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies. [ABSTRACT FROM AUTHOR]

Background and objective: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. Methods: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. Results: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58–2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60–2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75–1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83–4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08–3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85–2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15–2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93–2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46–1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. Conclusion: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events. Key points: This paper aims to perform a meta-analysis analyzing the efficacy and safety of eltrombopag for severe aplastic anemia. Our study suggests that EPAG added to IST is beneficial for patients with SAA. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to assess the prevalence and the burden of difficult‐to‐treat primary ITP (pITP), defined by the need for another ITP treatment after romiplostim and eltrombopag. Adult patients were selected in the prospective, real‐world CARMEN‐France registry up to December 2021. Out of 821 adult patients with pITP, 29 had difficult‐to‐treat ITP (3.5%; 95% confidence interval [CI]: 2.3%–4.8% in total; 7.6%; 95% CI: 4.9%–10.2% of patients needing ≥2nd line treatment). The 3‐year cumulative incidence of bleeding, infection and thrombosis was 100%, 24.1% and 13.8% respectively. The median cumulative duration of hospital stays was 31 days (median follow‐up: 30.3 months). [ABSTRACT FROM AUTHOR]

Background: While chimeric antigen receptor (CAR) T‐cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post‐treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post‐CAR T cytopenias using the thrombopoietin mimetic eltrombopag. Methods: This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T‐cell therapy at two academic medical centers. Eltrombopag was initiated for patients who had persistent high‐grade leukopenia and/or thrombocytopenia beyond 21 days post‐CAR T infusion. Risk factors and outcomes were assessed and compared for patients who did or did not receive eltrombopag. Results: Among the 185 patients analyzed, a majority (88%) experienced thrombocytopenia or leukopenia at day +30 post‐CAR T infusion. A total of 42 patients met the criteria for eltrombopag treatment and initiated therapy. Patients who received eltrombopag were more likely to have pre‐existing cytopenias at lymphodepletion, receive bridging therapy, experience an infection, or require intensive care. Recovery from cytopenias occurred within 180 days for a majority (94%) of patients. Conclusions: The use of eltrombopag for post‐CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post‐CAR T cytopenias might be effective in a high‐risk patient population but requires further study. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) are used in several advanced malignancies and may cause various immune-related adverse events (irAEs). Among them, hematological irAEs are less described. Acquired amegakaryocytic thrombocytopenia (AAT) is a rare immune hematologic disorder characterized by severe thrombocytopenia and complete absence of megakaryocytes in bone marrow. Case presentation: Herein, we present the case of a patient in their 40s with metastatic melanoma who developed an AAT after 12 cycles of nivolumab (anti-PD1). His platelet count decreased by =5 × 109/l without other cytopenia. Bone marrow biopsy showed normal cellularity with a complete absence of megakaryocyte and T-CD8+ lymphocyte infiltration. Given the failure of systemic steroids, eltrombopag was started, an oral thrombopoietin receptor agonist (TPO-RA), and his platelet count subsequently increased with complete response. Discussion: Four other cases are described on literature with the same features than non-ICI-related AAT. All cases occurred after anti-PD/PD-L1 treatment with a median onset of 5 weeks. The presentation of our case is quite different with delayed cytopenia. Both ciclosporin and TPO-RA seem to be efficient therapies. Conclusion: TPO-RA could be preferred in oncologic patients, but safety data are still missing to define clear guidelines for immune-related AAT management. [ABSTRACT FROM AUTHOR]

Summary: We have previously confirmed the efficacy and safety of eltrombopag (ELT) in children with chronic immune thrombocytopenia (cITP). However, data on both long‐term exposure and early use of TPO‐RAs are lacking, so further 'field‐practice' evidence on treatment is required. Here, we report the long‐term follow‐up results (between September 2018 and June 2023) of our previous study. The main objective of this study was to retrospectively review our large institutional experience with ITP patients previously enrolled in our paediatric cITP study. We had more than 3 years of follow‐up by June 2023 for treatment patterns and outcomes. A total of 65 patients (28 males) were enrolled, with a median age at ELT initiation of 6.34 (range 1.65, 14.13) years and a follow‐up of 47.07 (36.00, 57.00) months, with 40.36 (10.53, 56.83) months of ELT therapy at the time of analysis. In total, 29.23% (19/65) of patients discontinued ELT due to stable response, and 18.46% (12/65) of patients switched to other ITP therapies due to loss of response (LOR) after 19.13 (14.53, 26.37) months. Of the 19 patients who discontinued ELT due to a stable response, 24.62% (16/65) achieved a 12 m sustained response off‐treatment (SRoT); the last recorded platelet count ranged from 56 to 166 × 109/L (median 107 × 109/L); and 4.62% (3/65) patients relapsed at 5, 6 and 9 months after discontinuation. Of the 12 patients who LOR to ELT after 19.13 (14.53, 26.37) months of therapy, four switched to avatrombopag, three switched to hetrombopag, two switched to traditional Chinese medicine (TCM), one underwent splenectomy and two received additional prednisolone under ELT treatment. Thirty‐four patients who tapered and maintained a durable response. The patients with LOR and the patients with tapering were compared; the platelet count at the start of ELT is lower, and the time to response is longer in the patients with LOR. The platelet count at the start of ELT and the time to response may be the predictive factors for LOR during ELT treatment. We report more than 3 years of long‐term clinical data on children with cITP using ELT. These data do not raise any new safety concerns regarding the long‐term use of ELT in children with cITP. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a rare bone marrow failure disorder that is treated with either allogeneic stem cell transplant or immunosuppressive therapy (IST) consisting of antithymocyte globulin (ATG), cyclosporine (CSA), and eltrombopag. While outcomes are favorable in younger patients, older patients (>60) have significantly worse long‐term survival. The dose of ATG is often reduced in older patients and those with multiple comorbidities given concerns for tolerability. The efficacy and safety of dose‐attenuated IST in this population is largely undescribed. We performed a retrospective review of patients with AA treated with IST. Our analysis was confounded by changes in practice patterns and the introduction of eltrombopag. We identified 53 patients >60 years old, of which, 20 received dose‐attenuated IST, with no statistically significant difference in overall survival between full and attenuated dose cohorts. Overall response rates in both cohorts were similar at 6 months at 71% and 68%. There were more documented infectious complications in the full dose cohort (13 vs. 3). This supports the consideration of dose‐attenuated IST in older patients with concerns about tolerance of IST. Lastly, our data confirmed favorable outcomes of younger patients receiving IST, especially in combination with eltrombopag. [ABSTRACT FROM AUTHOR]

The treatment of aplastic anemia (AA) has significantly advanced in the last 50 years, evolving from a fatal condition to one where survival rates now exceed 80–85%. Hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have become the primary treatments, with the latter widely adopted due to factors like the scarcity of compatible donors, patient age, comorbidities, and limited HSCT access. A therapy breakthrough was the introduction of antithymocyte globulin (ATG), with its effectiveness further boosted by cyclosporine. However, it took years to achieve another major milestone in management. Initially, treatments aimed to intensify immunosuppression following the success of the ATG–cyclosporine combination, but these methods fell short of expectations. A major turning point was combining immunosuppression with stem cell stimulation, surpassing the efficacy of IST alone. Earlier, growth factors had shown limited success in AA treatment, but thrombopoietin receptor agonists represented a significant advancement. Initially applied alone as salvage, these were later combined with IST, forming the most effective current regimen for medically managing SAA. Horse ATG is the preferred formulation combined with cyclosporine and eltrombopag. This progress in AA treatment offers improved outcomes for patients afflicted with this once-lethal disease. [ABSTRACT FROM AUTHOR]

Importance: Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported. Objective: This study aims to explore the appropriate eltrombopag concentration in pediatric ITP. Methods: This was a single‐center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×109/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high‐performance liquid chromatography‐mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics‐concentration, concentration‐response, and concentration‐ADRs were analyzed. Results: A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response. Interpretation: Eltrombopag proves efficacious and well‐tolerated for treating pediatric ITP. However, prolonged and high‐dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP. [ABSTRACT FROM AUTHOR]

Introduction: Novel treatment strategies for newly diagnosed immune thrombocytopenia (ndITP) pediatric patients are required. Material and methods: The aim of this study was to analyze the safety and efficacy of eltrombopag and dexamethasone when used as the first-line treatment in children with ndITP. Inclusion criteria: age 5-18 years, and ndITP with bleeding manifestation. Treatment course: 28 days of eltrombopag with oral dexamethasone in three repeated courses. Results: A complete response was achieved in 90% of patients after the first week of treatment, and in all patients after the end of the treatment course. Durable and sustained platelet response was observed in 90% of patients after 12 months of follow-up. Conclusions: Our finding support safety and efficacy of eltrombopag and dexamethasone as combined first-line therapy of ndITP in children. [ABSTRACT FROM AUTHOR]

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The purpose of this study is to investigate the molecular interactions and potential therapeutic uses of Eltrombopag (EPAG), a small molecule that activates the cMPL receptor. EPAG has been found to be effective in increasing platelet levels and alleviating thrombocytopenia. We utilized computational techniques to predict and confirm the complex formed by the ligand (EPAG) and the Thrombopoietin receptor (TPO-R) cMPL, elucidating the role of RAS, JAK-2, STAT-3, and other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed to evaluate the stability of the ligand across specific proteins, showing favorable characteristics. For the first time, we examined the presence of TPO-R in human umbilical cord mesenchymal stem cells (hUCMSC) and human gingival mesenchymal stem cells (hGMSC) proliferation. Furthermore, treatment with EPAG demonstrated angiogenesis and vasculature formation of endothelial lineage derived from both MSCs. It also indicated the activation of critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, and FLI-1. Additional experiments confirmed that EPAG could be an ideal molecule for protecting against UVB radiation damage, as gene expression (JAK-2, ERK-2, MCL-1, NFkB, and STAT-3) and protein CD90/cMPL analysis showed TPO-R activation in both hUCMSC and hGMSC. Overall, EPAG exhibits significant potential in treating radiation damage and mitigating the side effects of radiotherapy, warranting further clinical exploration. [ABSTRACT FROM AUTHOR]

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Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: The introduction of thrombopoietin receptor agonists (TPO‐RAs) led to a paradigm shift in the management of immune thrombocytopenia (ITP). However, TPO‐RAs are not approved for use during pregnancy due to the absence of evidence and concerns for possible effects on the fetus due to their expected transplacental transfer. This comprehensive review examines the safety and efficacy of TPO‐RA in 45 pregnancies of women with ITP (romiplostim n = 22; eltrombopag n = 21; both in the same pregnancy n = 2). Mothers experienced failure of the median of three treatment lines during pregnancy prior to TPO‐RA administration. A platelet response (>30 × 109/L) was seen in 86.7% of cases (including a complete response >100 × 109/L in 66.7%) and was similar between eltrombopag and romiplostim (87.0% and 83.3%, p = 0.99). The maternal safety profile was favourable, with no thromboembolic events encountered. Neonatal thrombocytopenia was noted in one third of cases, with one case of ICH grade 3, and neonatal thrombocytosis was observed in three cases. No other neonatal adverse events attributable to TPO‐RAs were seen. This review suggests that the use of TPO‐RA during pregnancy is associated with a high response rate and appears safe. Nevertheless, TPO‐RA should not be routinely used in pregnancy and should be avoided in the first trimester until further evidence is accumulated. [ABSTRACT FROM AUTHOR]