Chronic Immune Thrombocytopenic Purpura Research Articles

Additive and Dose-Dependent Effect of Rituximab on Pediatric Patients’ Outcomes Concurrently Receiving Immunosuppressive Chemotherapy, A Prospective Cohort Study

Background: Rituximab (RTX) is approved for treating CD20-positive B-cell malignancies, including non-Hodgkin lymphoma, when used alongside chemotherapy. It has the potential to interact with and alter the host immune system, putting patients at a heightened risk of infection. Therefore, the use of RTX necessitates a meticulous assessment of infectious risks based on the latest evidence. Objectives: We conducted a prospective investigation into infectious complications and mortality among children undergoing RTX treatment over the observation period of the study. Methods: In this observational cohort study, we included 61 pediatric patients treated with RTX for malignancy and immune thrombocytopenic purpura (ITP), as well as 122 cancer patients who had never received RTX (the unexposed group). These patients were prospectively monitored for febrile neutropenia (FN), bloodstream infection (BSI), invasive fungal infection (IFI), and mortality. All infectious complications were documented starting from the initial dose of RTX and continuing for at least six months following the last dose. Logistic regression and Cox regression analyses, with consideration for the proportional hazards assumption, were utilized to evaluate the impact of covariates on mortality and infection-related outcomes. Results: Infectious complications were observed in 52.5% of children treated with RTX. These complications were notably more prevalent in children with malignancy compared to those with chronic ITP (89.5% versus 10.5%, respectively). RTX was found to be associated with an increased likelihood of mortality in children with malignancy (OR [95% CI]: 1.54 [0.41, 5.69]). According to Cox regression analysis, RTX was linked to a higher risk of IFIs, death, FN events, and BSIs over a 36-month observation period (4.33 [1.21, 15.52], 3.26 [1.008, 10.59], 1.68 [0.83, 3.41], and 1.59 [0.27, 9.17], respectively). The total dose of RTX administered was also associated with adverse patient outcomes, with the odds of infectious events and death increasing in the second, third, and fourth quartiles of the total RTX dose administered. Furthermore, the estimated one-year and two-year survival rates for cancer patients treated with RTX were 77% and 58%, respectively. Conclusions: RTX treatment, when used concurrently with immunosuppressive chemotherapy for hematologic malignancies in children, showed additive and dose-dependent effects on clinical outcomes.

Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients.

Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.

Antinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus

AbstractAutoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS’CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.

MYH9-related diseases in the differential diagnosis of chronic immune thrombocytopenic purpura

Myosin heavy chain 9 (MYH9)-related platelet disorders (MYH9-RD) belong to the group of inherited thrombocytopenias characterized by giant platelets and Döhle bodies. The process leading to the diagnosis of MYH9-RD in a 13-year-old male patient, followed by the diagnosis of chronic immune thrombocytopenic purpura (ITP), is described. The patient had thrombocytopenia with increased mean platelet volume since he was a little boy. Low CD41, CD42 and CD61 levels were detected in blood tests sent to complete missing diagnostic tests. Platelet aggregation tests were also abnormal. The requested genetic test revealed a heterozygous mutation in the MYH9 gene. The patient’s audiogram and kidney functions were normal. In conclusion, because MYH9-RD appears to be rare, it is of great importance to maintain a high index of suspicion when managing patients diagnosed with chronic ITP. Additional complaints and findings should be considered at every outpatient clinic examination to make a more accurate diagnosis and prevent unnecessary treatments.

Development and Validation of a UV Spectroscopic Method to Estimate Eltrombopag Olamine along with Bulk and In-house Formulation

The current UV Spectroscopic method developed involving ethanol as a solvent is simple, fast, specific, precise, and sensitive for the estimation of Eltrombopag Olamine in bulk in day-to-day analysis. As per the ICH Q2 (R1) guideline, the method was validated. Eltrombopag Olamine is a drug used to treat thrombocytopenia (a low blood platelet count) in adults and youngsters with chronic immune idiopathic thrombocytopenic purpura that didn't get well with different treatments. Eltrombopag Olamine is additionally accustomed to treating severe aplastic anemia. It’s conjointly being studied within the treatment of different conditions and kinds of cancer. Eltrombopag Olamine binds to the thrombopoietin receptor, which causes the bone marrow to create more platelets. It’s class of thrombopoietin receptor agonists, also known as Promacta. Eltrombopag is also recently approved (2012) for the treatment of thrombocytopenia in a patient with chronic hepatitis C to start and sustain interferon-based therapy. The solvent used in the entire method development and validation was ethanol. The maximum wavelength of absorption was found to be 423nm. Beer’s law was obeyed in the concentration range of 5 to 30ug/ml with a correlation coefficient of 0.9966. The method was precise with an RSD of less than 2%, the LOD, and LOQ were found to be 6.18ug/ml and 18.7ug/ml respectively, % recovery of the drug is 98 to 100%. The method was validated for linearity, precision, accuracy, and robustness and all parameters were found to be satisfactory which proves that this method can be used for routine analysis of Eltrombopag Olamine.

A cost-utility analysis of thrombopoietin receptor agonists for treating pediatric immune thrombocytopenia purpura after failure of first-line therapies.

Thrombopoietin receptor agonists (TPO-RAs) have emerged as a recommended treatment for children with persistent and/or chronic immune thrombocytopenic purpura (ITP). The purpose of this study was to evaluate the cost-effectiveness of TPO-RAs relative to treatment without TPO-RAs (non-TPO-RAs/usual care) for ITP in children who do not respond to first-line therapy and in whom splenectomy is not recommended in Ontario, Canada, from a hospital payer perspective. A 2-year Markov model with an embedded decision tree was used. Data on medications used, dose, response rate, bleeding, and emergency treatment events were collected from the Hospital for Sick Children in Toronto. The health outcomes were described in quality-adjusted life-years (QALYs). Health-state utilities were derived from the peer-reviewed literature. Scenario analyses, deterministic, and probabilistic sensitivity analyses were conducted. Economic costs were measured in 2021 Canadian dollars ($1.00=US$0.80) RESULTS: TPO-RAs are estimated to result in an increased cost of $27,118 and a QALY gain of 0.21 compared to non-TPO-RAs over a 2-year horizon, resulting in an incremental cost-effectiveness ratio (ICER) of $129,133. In a 5-year scenario analysis, the ICER fell to $76,403. In the probabilistic sensitivity analysis, TPO-RAs exhibit a 40.0% probability of being cost-effective at a conventional ($100,000) willingness-to-pay threshold per QALY gained. Further assessment of the long-term efficacy of TPO-RAs is warranted to obtain more precise long-term estimates. As the costs of TPO-RAs decline with the introduction of generic formulations, TPO-RAs may be increasingly cost-effective.

Ayurvedic management of immune thrombocytopenic purpura - a case report

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by isolated thrombocytopenia. The course is more chronic in adults associated with higher mortality in older patients. In extreme cases of ITP, serious complications such as bleeding into the lungs, brain, or other vital organs can occur. Clinical manifestations include purpura, petechiae and ecchymosis. Majority of ITP patients are not getting reliable and durable remissions with modern medicine. The present case report deals with an elderly patient having chronic ITP with multiple comorbidities (obesity, schizophrenia, UTI and T2DM) approached for Ayurvedic treatment. Patient came with ecchymotic patches on both upper extremities with extremely low platelet counts (9700/mcL) was diagnosed as Tiryaggata Raktapitta and Ayurvedic treatment has been provided. Ayurvedic formulations (Putapakwa Vishama Jwarantaka Loha, Raktastambhaka Vati, Samshamani Vati etc) have improved the platelet counts (from the lowest count of 9700/mcL to highest count of 50000/mcL), hematological indices and quality of life in present case. Ecchymotic patches were completely disappeared without any further recurrences. The present case of ITP (Raktapitta) is a good example for Nidaanaarthakara Roga as it has manifested due to the consequences of malarial fever (Vishama Jwara). Ayurvedic treatment seems to be promising in the management of chronic ITP and generates hope for those patients who are having extreme thrombocytopenia, multiple comorbidities, reluctant (or unfit) for corticosteroids and invasive diagnostic procedures like bone marrow biopsy, and not satisfied with the available therapy from other systems of medicine. Further clinical trials with large sample size are required to substantiate the present case study findings.

Don't neglect the rare adverse event with intravenous immunoglobulin: Hemolytic anemia.

Intravenous immunoglobulin (IVIG) associated hemolytic anemia is an under-recognized complication of IVIG therapy. The incidence of this adverse event is not clear. Patients at high risk for IVIG-associated hemolytic anemia include non-O blood group recipients and those undergoing high-dose administration for inflammatory or autoimmune disorders. Here, two different cases of IVIG-associated hemolytic anemia are demonstrated. The first patient, a 66year-old male with Guillain-Barré syndrome, had a severe attack for which erythrocyte replacement was required. Mild hemolysis was detected during IVIG administration in the second patient, a 57year-old female with chronic immune thrombocytopenic purpura. Following IVIG termination, the hemolysis diminished gradually. Although it is rare and often manageable, clinicians should be aware of and monitor patients for hemolytic anemia following IVIG therapy.

Role of Long non Coding RNAs, NEAT1 and Lnc-DC Expression in Pediatric Immune Thrombocytopenic Purpura.

Pediatric immune thrombocytopenic purpura (ITP) is an autoimmune disease; whose etiology is unknown. lncRNAs are regulators of numerous actions, which participate in the development of autoimmune diseases. We evaluated the expression ofNEAT1 and Lnc-RNA in dendritic cell (Lnc-DC) in pediatric ITP. Sixty ITP patients and 60 healthy subjects were enrolled in the present study; Real-time PCR was performed to assess the expression levels of NEAT1 and Lnc-DC in sera of children with ITP as well as healthy children. Both lncRNAs, NEAT1 and Lnc-DC were significantly upregulated in ITP patients in comparison to controls (p <0.0001 and P= 0.001 respectively). Furthermore, significant upregulation of the expression levels of NEAT1 and Lnc-DC were observed in the non-chronic compared with chronic ITP patients. Also, there was significant negative correlation between each of NEAT1 and Lnc-DC and platelet counts before treatment (r= -0.38; P= 0.003 and r= -0.461; P< 0.0001, respectively). serum lncRNAs, NEAT1 and Lnc-DC could be used as potential biomarkers in differentiating childhood ITP patients and healthy controls in addition to differentiating non-chronic from chronic ITP which may provide a theoretical basis for the mechanism and treatment of immune thrombocytopenia.

The Safety and Efficacy of Fostamatinib in Patients with Chronic Immune Thrombocytopenic Purpura Treated in a Real-World Community Hematology Setting

Background: Chronic immune thrombocytopenia (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment with corticosteroids is intended to suppress the immune response and is effective in many patients but not sustainable. Fostamatinib is an approved therapy for adult patients with ITP who have had an insufficient response to a prior treatment. It is an oral small molecule that targets spleen tyrosine kinase (SYK), which has important roles in cellular proliferation, differentiation, and immune regulation. By blocking SYK, fostamatinib reduces the immune system's destruction of platelets, which allows the platelet (PLT) count to rise, thereby reducing the risk of bleeding in ITP patients. Two placebo-controlled randomized trials demonstrated that fostamatinib was well tolerated and able to induce meaningful platelet responses in heavily pretreated patients, as well as in earlier lines of therapy. The use of fostamatinib in a community hematology setting has not been evaluated. In this study, the real-world utilization and treatment patterns of fostamatinib in patients treated within the QCCA, a network of 17 community hematology clinics across the United States, is presented. Methods: The QCCA network real world database was reviewed for ITP patients who had received fostamatinib over the past 3 years. Data collection consisted of patient demographics, disease characteristics, duration of ITP, existing comorbidities, number and type of prior ITP treatments and PLT count at baseline prior to the start of fostamatinib. All of the information was collected via a standardized data collection form. From the first day until the end of treatment, data were collected on hemoglobin, white blood cells, absolute neutrophil counts, PLT counts, concomitant ITP therapies and the use of rescue IVIG. A meaningful increase in PLTs was defined as achievement of platelet counts ≥ 30 and ≥ 50 x 103/μL over the course of therapy. Results: The medical records of the 46 ITP patients who met the inclusion criteria and received fostamatinib were evaluated. Patients had a median age of 58 years, 65% were female and 35% had a splenectomy. All patients had prior exposure to corticosteroids and the median number of therapies before stating fostamatinib was two. In addition, 65% had received thrombopoietin receptor agonists and rituximab. All patients started therapy at a dose of 100 mg twice daily for a median duration of 2 months (interquartile range [IQR] = 1 to 15) and a mean duration of 6.7 months (95%CI: 3.5 to 9.9). When fostamatinib was started, the median PLT count was 19 x 103/μL (IQR = 3 to 70). From the start of therapy, the maximum increase in the median PLT count was 78 x 103/μL (IQR = 13 to 231), which was achieved after a median of 1.8 months. Over the course of therapy, 31 (67.4%) and 26 (56.5%) of 46 patients achieved or maintained PLT levels ≥ 30 and ≥ 50 x 103/μL respectively. Of note, prior to the start of fostamatinib, 9 and 7 patients respectively, already had PLT levels ≥ 30 and ≥50 x 103/μL. The percent of patients with at least a doubling of their baseline PLT count was 47.8% (95%CI: 32.9 to 63.0%). There were no serious bleeding events reported, and only one patient required the discontinuation of fostamatinib because of adverse events. Among the 46 patients, 16 received concomitant IVIG to increase PLT counts. Conclusions: In this real-world setting, the findings suggest that fostamatinib is safe and effective in patients with chronic ITP who had relapsed or had not responded to one or more prior treatments.

The Role of Bone Marrow Aspiration in Diagnosis of Hypersplenism and other Diseases in Kassala Area Eastern Sudan, October 2016-October 2017

Introduction: Bone marrow aspiration (BMA) is an important tool in diagnosis of many haematological and non-haematological diseases. BMA usually done together with complete blood cell count (CBC) and peripheral blood picture. BMA needed for diagnosis of hypersplinsm. BMA alone is sufficient for diagnosis of megaloblastic anaemia, microcytic anaemia, acute leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia and immune thrombocytopenic purpura (ITP). The objective of this study was to determine the indication of bone Aspiration (BMA) in Kassala state eastern Sudan. Identify the important of BMA in diagnosis of hyperslenism and other diseases in the area. Methodology: All cases for BMA referred from different hospitals and health centres in Kassala state. Seventy-one cases of bone marrow aspiration conducted at the Department of Pathology Faculty of Medicine, Kassala University from October 2016 to October 2017. Blood cell count and peripheral blood picture done for all patients subjected for bone marrow aspiration. Clinical information, physical examination, BMA results and other investigations recorded in specially designed form. Data entered on SPSS version 15 and statistically analyse. Results: In 71 of patients underwent BMA, 46 (64.8%) of them with splenomegaly. Twenty (44%) of patients with splenomegaly was due to bilharzia, 18 (39%) due to malaria, two due to malignancy (4%), two (4%) due Visceral Leishmaniosis and two unrevealed causes. Out of the cases with splenomegaly 34 (73.9%) showed features of hypersplenism. Non-splenomegaly cases, 8(32%), 3(12%), 2(8%), iron deficiency, haemolytic, aplastic, and megaloblastic anaemia respectively. 4 cases diagnosed as Idiopathic Thrombocytopenia (ITP). Two cases diagnosed as acute leukaemia. Conclusion: Bone marrow aspiration was very important tool for diagnosis of hypersplenism, endemic diseases in the area and other haematological disorders.

Antibody waning after immunosuppressive chemotherapy and immunomodulators, re-immunization considerations in pediatric patients with malignancy and chronic immune thrombocytopenic purpura

IntroductionImmunosuppressive chemotherapy increase the risk of vaccine-preventable infectious diseases in children; nevertheless, chemotherapy may result in delay or miss updated immunization schedules. The predictable antibody waning after incomplete primary immunization series may be intensified at the end of chemotherapy. This study aimed to investigate post-chemotherapy vaccine immunity waning at the end of immunosuppressive therapy in children with malignancy and hematologic disorders.Materials and methodsChildren with malignancies and hematologic disorders including chronic immune thrombocytopenic purpura (ITP) younger than 18 years old were enrolled from September 2015 to August 2019. Eligible patients who completed their treatment protocol for at least 6 months were recruited. The patient information, including sex, age at the date of diagnosis, number of chemotherapy sessions, underlying disease, and vaccination history, was taken by chart review using predefined questionnaires. The patient’s blood samples were obtained, and serum IgG antibody titer checked against diphtheria, tetanus, hepatitis B virus (HBV), mumps, measles, and rubella (MMR) were measured by enzyme-linked immunosorbent assay (ELISA).Results110 children receiving immunosuppressive chemotherapy were recruited. Forty-four (40%) of the children tested were girls and 66 (60%) were boys. The mean age of patients was 5.5 years with a range of 2 to 13 years. Of 110 studied children, 27.3% were seronegative for all antibodies. On average, patients undergo 19 episodes of chemotherapy. The mean chemotherapy sessions were significantly greater in children who were seronegative for all tested antibodies (mean: 36.2, 95% CI 33.16 to 39.24, p-value < 0.001). No statistically significant differences were observed regarding the patient’s sex and age between the seropositive and seronegative groups (p-value 0.513 and 0.060, respectively). Based on Poisson regression model analysis, the female gender was associated with 37% lower odds of seronegativity (incidence rate ratio (IIR): 0.63; [95% conf. interval: 0.39 to 1.01, p-value: 0.55]), while chemotherapy sessions 30 or more was associated with significant odds of seronegativity for all tested vaccines (IIR: 25.41; [95% conf. interval: 6.42 to 100.57, p-value < 0.001]).ConclusionOur results reemphasized planned catchup immunization in children undergoing immunosuppressive chemotherapy for malignancy, especially against tetanus, diphtheria, and hepatitis B at least 6 months after the end of chemotherapy sessions.

Efficacy and safety of rituximab as second-line therapy in immune thrombocytopenic purpura based on ethnicity: A descriptive study among the Arabic population.

Background: Rituximab is used as second-line therapy in patients with immune thrombocytopenic purpura (ITP) who do not respond to first-line management. The response rate for Rituximab is variable in different populations ranging from 30% to 90%. The adverse effects of rituximab in patients with ITP range from infusion site reactions to the reactivation of hepatitis B virus and progressive multifocal leukoencephalopathy and interpopulation variation.Methods: We conducted a single-center, retrospective study in Qatar's National Center for Cancer Care & Research. The study included patients with chronic refractory ITP who received rituximab as second-line therapy. Descriptive and summary statistics were used to describe the sociodemographic parameters of the study cohort.Results: Of the 41 patients with chronic ITP, 26 were Arabs, 12 were Asians, and 3 were of other ethnicities. Rituximab was associated with an overall response rate of 80.4%. Arabic patients had the highest clinical response (84.6%) among the ethnicities with the lowest adverse effects (11.5%). Asians had a response rate of 66.6%, and adverse effects were seen in 16.7% of the patients.Conclusions: In chronic refractory ITP, rituximab appears to have a better clinical response in the Arabic population with minimal toxicity than in other ethnicities.

Effect of Helicobacter pylori infection on the first-line treatment outcomes in patients with immune thrombocytopenic purpura.

Helicobacter pylori (H. pylori) eradication therapy is known to increase the platelet count, but in immune thrombocytopenic purpura (ITP), the effect of H. pylori infection on the response to treatment is not clear. This study aims to determine whether the response to the first-line treatment is affected by the states of H. pylori-positivity and -negativity in ITP patients. Adult newly diagnosed or chronic ITP patients who had not received eradication therapy for H. pylori infection were included. Characteristics of the patients, presence and severity of bleeding, initial platelet count, administered treatments, and treatment response rates were inspected. Of 119 total patients, 66 (55.5%) were female, 32 (26.9%) were H. pylori-positive, 87 (73.1%) were H. pylori-negative. H. pylori-positive and H. pylori-negative groups were not significantly different in terms of age (p=0.127), gender (p=0.078), diagnosis status (p=0.094) and the distribution of bleeding symptoms (p=0.712). The most common treatment was standard-dose steroid in both groups (62.5% vs. 68.9%, p=0.524). Rates of complete response, partial response, no response were comparable for the two groups (respectively, 75% vs. 73.6%, and 18.8% vs. 19.5%, and 6.2% vs. 6.9%), and there was no significant difference between the groups (p=0.283). It can be stated according to the present study that in ITP patients in whom treatment is indicated, the response to the first-line treatment without the administration of H. pylori eradication therapy is similar between H. pylori-positive and H. pylori-negative patients.

Role of Ca2+, Calnexin and Calreticulin in Platelet from Adult Patients with Chronic Immune Thrombocytopenic Purpura.

BackgroundAdult chronic immune thrombocytopenia (chronic ITP) is a common autoimmune hemorrhagic disease characterized by decreased platelet production and increased platelet destruction, leading to thrombocytopenia. In this study, Ca2+, calnexin (CNX) and calreticulin (CRT) within platelets from adult patients with chronic ITP were investigated.MethodsPlatelets were isolated from blood specimen collected from 20 adult patients with chronic ITP and 20 healthy volunteers. Ca2+, CNX and CRT were determined by flow cytometry, and the results were analyzed with EXPO32 ADC software.ResultsFlow cytometry showed the expressions of Ca2+ (74.19±19.40% vs 22.79±10.47%) was elevated (P<0.05). However, CNX (15.10±7.32% vs 41.79±14.45%) and CRT (25.11±12.66% vs 38.58±12.02%) were decreased markedly in platelets from adult patients with chronic ITP (P<0.05 compared with healthy volunteers).ConclusionBased on enhanced expression of Ca2+ and attenuated expression of CNX and CRT in patients with chronic ITP, Ca2+ concentration and its associated down-regulated proteins may be important regulatory signals in the pathogenesis of chronic ITP.

Evaluation of Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag: A Single Center Experience

Evaluation of Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag: A Single Center Experience

Assessment of plasmablast cells in immune thrombocytopenic purpura in children

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

Updated guidelines for immune thrombocytopenic purpura: Expanded management options.

The current American Society of Hematology (ASH) guidelines for the management of patients with immune thrombocytopenic purpura (ITP) are an update to the 2011 guidelines. The updates focus on treating patients with ITP without bleeding in both outpatient and inpatient settings, including those with newly diagnosed, persistent, and chronic ITP refractory to first-line therapy. Recommendations for therapy include corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists, as well as observation.

Infections in Secondary Immunodeficiency Patients Treated with IgPro10: A Real-Word Analysis of Patients, Including Those with Hematological Malignancies

▪Secondary immunodeficiency (SID) is an acquired condition caused by several factors including, but not limited to, B-cell malignancies, and may result in frequent, burdensome, and possibly life-threatening infections. Treatment guidelines recommend immunoglobulin replacement therapy (IgRT) in certain settings to prevent recurrent, persistent, or major (severe) infections. This retrospective analysis of a US healthcare database characterized patients (pts) with suspected SID, who experienced infections, and were or were not treated with IgRT (IgPro10 [Privigen ®]).Data were collected from 26 US healthcare organizations from TriNetX DataWorks™ Network between 1/1/09 - 1/31/20. Pts were required to have the following: suspected SID (defined as ≥1 underlying conditions related to SID such as: solid organ transplant [SOT], non-Hodgkin lymphoma [NHL], multiple myeloma [MM], and chronic lymphocytic leukemia [CLL]), ≥1 severe infection (defined as requiring hospitalization and/or treatment with intravenous antibiotics or anti-viral medication) or ≥2 non-severe infections between underlying condition diagnosis date and the index date, the absence of diagnosed primary immunodeficiency, and an available medical history of ≥12 months pre-index and ≥3 months post-index. The index date refers to first IgPro10 use or the corresponding date for pts not receiving IgPro10 (unexposed cohort). In the IgPro10 cohort, pts were required to have had ≥2 consecutive IgPro10 administrations within 90 days. Between the pre- and post-index periods, the following variables were compared for both cohorts: pts' treatment, underlying conditions, baseline characteristics, and change in annualized infection rate (for infections of any severity and severe infections). Pre-index immunoglobulin G (IgG) (or calculated globulin [CG]) levels were recorded as: hypogammaglobulinemia (HGG) (IgG <6 g/L or CG <18 g/L), normal (IgG ≥6 g/L or CG ≥18 g/L), or missing. A generalized estimation equation (GEE) model with logit link was used to compare the change in the proportion of pts with an annualized infection rate of zero from the pre- to the post-index period across both cohorts.The final sample comprised 222 IgPro10 pts and 11,226 unexposed pts. In the IgPro10 cohort, 143 pts were on IgPro10 for <6 months, 41 pts for 6-12 months, and 38 pts for >12 months. In both the IgPro10 and the unexposed cohorts, SOT was the most frequent underlying condition (45.5% and 44.6%, respectively), followed by NHL (21.6% and 28.2%, respectively), MM (14.4% and 10.1%, respectively), and CLL (11.3% and 7.6%, respectively). Age (mean [SD], 57.2 [13.9] vs 57.9 [17.0] years old, respectively) and sex distribution (male:female, 56.3%:43.7% vs 51%:48.8%, respectively) were similar in the IgPro10 and unexposed cohort. During the pre-index period, the IgPro10 cohort, compared with the unexposed cohort, received a greater number of antibiotic courses (median [interquartile range], 7 [20] vs 1 [5], respectively), had a substantially higher proportion of pts with HGG (HGG: 34.7% vs 3.0%; normal IgG: 43.7% vs 57.8%; missing: 21.6% vs 39.2%, respectively), and a lower proportion of pts with an annualized infection rate of zero (for infections of any severity and severe infections) (Figure 1). There was an approximate four-fold increase in the proportion of pts with no infections of any severity following IgPro10 administration; this increase was significantly larger than in the unexposed cohort (p<0.0001) (Figure 1). Additionally, there was an increase in the proportion of pts with no severe infections following IgPro10 administration. Again, this increase was significantly larger than in the unexposed cohort (p<0.0001) (Figure 1).This real-world study found that compared with pts not receiving IgRT, pts who subsequently went on to receive IgPro10 experienced more infections pre-treatment. Following IgPro10 administration, more pts had an annualized infection rate of zero (for infections of any severity or severe infections) compared with the pre-index period. Moreover, the increase in the proportion of pts with no infections was greater in the IgPro10 cohort than in the unexposed cohort, for both infections of any severity and severe infections. Taken together, these findings suggest effectiveness of IgPro10 in pts with SID, but further study, such as a prospective randomized controlled trial, is needed to confirm these initial findings. [Display omitted] DisclosuresLahue: CSL Behring: Consultancy; Alkemi Health: Current Employment, Current holder of stock options in a privately-held company. Mallick: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Koenig: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Espinoza: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. OffLabel Disclosure:IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, U.S.), a type of immunoglobulin replacement therapy, is currently approved in the U.S. to treat patients with primary immunodeficiency (PI), chronic inflammatory demyelinating polyneuropathy (CIDP), and chronic immune thrombocytopenic purpura (ITP).

Safety and Efficacy of Thrombopoietin Analogs in the Treatment of Chronic Thrombocytopenic Purpura in Children: A Systematic Review

IntroductionImmune thrombocytopenic purpura (ITP) is an autoimmune disorder consisting of low platelet count, purpura, and hemorrhagic episodes, caused by antiplatelet autoantibodies. Children who develop chronic or refractory ITP are at risk of bleeding after failing first-line therapies. Thrombopoietin analogs -Eltrombopag and romiplostim are safe and effective treatment options. Thrombopoietin receptor agonists (TPO-Ras) improve platelet production by activating the thrombopoietin pathway. They also stimulate megakaryocytes and hematopoietic stem cells. We analyzed the efficacy and toxicity of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura in the pediatric population (1-17 years).Materials/MethodsFollowing the PRISMA guidelines, we performed a comprehensive literature search on Pubmed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov. We used the following keywords, “Thrombopoitein analogs”, “TPOs”, “Immune thrombocytopenic purpura”, “Eltrombopag” and “Romiplostim” MeSh terms from the inception of data till 06/17/2021. We screened initial results from the search of 358 articles focusing on the pediatric population and finally included 9 clinical trials and 1 observational study. We excluded all case reports, case series, preclinical trials, review articles, and meta-analyses. We extracted the data for efficacy (platelet response, baseline platelet count, and Platelet count at first response) and safety (Bleeding or Grade ≥ 3 Adverse Events).Results:RomiplostimA total of 185 patients were analyzed in five clinical trials and 1 observational study employing Romiplostim in the treatment group. Platelet response (PR) (platelet count >50 × 109/L) has been reported in all the studies. In 3 randomized double-blinded control trials by Bussel 2011, Elfaly 2011, and Tarantino 2016, Romiplostim achieved a platelet response of 81.69% vs 12.9% in the placebo group.The other three studies reported substantial platelet response as stated in table 1. In all the studies 25 participants had a prior splenectomy. The most common side effects reported in the studies were bleeding (56.75%), headache (58.64%), contusion (50.76%), and epistaxis (49.23%). Clinically significant bleeding (grade 2-4) was reported by 2 studies in Romiplostim vs placebo group (71.08% vs 96%).EltrombopagA total of 246 patients were analyzed in five clinical trials and 1 observational study. In a randomized double-blinded multicenter study by Grainger et al., Eltrombopag achieved a PR of 39.68% vs 3.4% in the placebo group. Other clinical trials reported a PR of 55.85% whereas the observational study by Neuner et al. reported a PR of 72% in the patient population. Clinically significant bleeding was reported by Grainger et al. and was 47 % in the eltrombopag group vs 7% in the placebo group. Fifteen patients in all the studies had a prior splenectomy.Conclusion:Thrombopoietin analogs such as romiplostim and eltrombopag show substantial platelet response and are associated with minimal side effects. However, more randomized clinical trials are needed to compare their head-to-head efficacy and safety in the treatment of chronic immune thrombocytopenic purpura in pediatric patients. [Display omitted] DisclosuresAnwer: Janssen pharmaceutical: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding.