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The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial‐and‐error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu et al.'s study which developed ML‐based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice. Commentary on: Xu et al. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024; 205:1108‐1120. [ABSTRACT FROM AUTHOR]

Summary: Autoimmune haemolytic anaemia (AIHA) is a rare complication of allogeneic haematopoietic stem cell transplantation (HSCT), observed with an incidence of 1–5%. Paediatric age, diagnosis of non‐malignant disease, lympho‐depleting agents in the conditioning regimen, use of unrelated donor, graft versus host disease and infections have been associated with a higher risk of AIHA post HSCT. Post‐HSCT AIHA is associated with high mortality and morbidity, and it is often very difficult to treat. Steroids and rituximab are used with a response rate around 30–50%. These and other therapeutic strategies are mainly derived from data on primary AIHA, although response rates in post‐HSCT AIHA have been generally lower. Here we review the currently available data on risk factors and therapeutic options. There is a need for prospective studies in post‐HSCT AIHA to guide clinicians in managing these complex patients. [ABSTRACT FROM AUTHOR]

The management of patients with immune thrombocytopenia ( ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins ( IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. [ABSTRACT FROM AUTHOR]

Most children with immune thrombocytopenia ( ITP) have transiently low platelet counts and do not suffer from bleeding. Treatments with steroids, immunosuppression or splenectomy are not thought to be curative and may create more problems than the low platelet count. Consequently, many children do not receive treatment unless there is bleeding. However, although registry data looks promising, this approach outcome is not consistent between countries, or even between centres in the same country, leading to confusion for both physicians and families. Reaching a consensus for the management of paediatric ITP is further complicated by the lack of a diagnostic test and by the heterogeneity of the disease; for example, although most children remain relatively asymptomatic and go into an early remission, some patients have significant bleeding and others do not go into spontaneous remission. This review assesses the available evidence to guide physicians and families on making management decisions, showing the wide range of treatment choices, and the different approaches between countries and considers methods by which further information could be acquired to provide a more stratified approach to management. [ABSTRACT FROM AUTHOR]

Depletion of B lymphocytes using the anti-CD20 monoclonal antibody rituximab has wide-spread use in the treatment of patients with autoimmune disorders. As haematopoietic progenitor cells and only a fraction of differentiated plasma express CD20, the effect of rituximab on immune function appears to be minimal. However, hypogammagobulinaemia can occur with repeated doses and emerging data from large studies suggest a subtle increase in the risk of infection. Reactivation of latent JC virus, resulting in progressive multifocal leucoencephalopathy, and hepatitis B virus, resulting in hepatoxicity, have been documented in patients receiving rituximab; although confounding effects of concomitant immunosuppressive therapies and immune dysregulation due to the underlying disease make causal associations of infections problematic. This review discusses the efficacy of B cell depletion therapy in the treatment of autoimmune diseases, the effect of B cell depletion on infection and immunity including the role of the B cell in autoimmunity, and identifies areas of controversy. [ABSTRACT FROM AUTHOR]

Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP. [ABSTRACT FROM AUTHOR]

The article discusses the study "Rituximab as Second-Line Treatment for Adult Immune Thrombocytopenia (the RITP Trial): A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial" by Waleed Ghanima and colleagues, published within the issue. Topics covered include the efficacy of rituximab monotherapy as a second-line therapy for adult immune thrombocytopenia, the role of B-cell depleting therapy, and the long-term effects of rituximab on the memory B-cell population.

The article presents information on the diagnosis of autoimmune lymphoproliferative disorder type III with rituximab in a 10-year old boy. Due to repeated episodes of idiopathic thrombocytopenic purpura (ITP) and autoimmune neutropenia and following three courses of steroids, he received rituximab 375 mg weekly in July 2002. This lead to a complete resolution (CR) of both ITP and autoimmune neutropenia and virtual disappearance of lymphadenopathy.

Abstract Despite the improvement in understanding its pathogenesis and the introduction of novel treatment options, the management of primary immune thrombocytopenia (ITP) still remains challenging. Considering its increased incidence with aging and prolonged life-expectancy, ITP is often diagnosed in elderly patients, a subset that deserves some special precautions. Ensure the diagnosis is a crucial step, and carefully attention must be given in excluding other causes of thrombocytopenia, especially among older people that frequently suffer from many comorbidities. When it comes to treatment decision, it is worth keeping into account that the elderly have an increased risk of bleeding, thrombosis and infections, that they often require many concomitant therapies, including antiplatelet or anticoagulant agents, and that treatment-related toxicities are often increased and sometimes more dangerous that the disease itself. There are not dedicated guidelines, and only few specific studies. Steroids with or without IVIG remain the first-line treatment. Splenectomy is less effective than in youngers and burdened by an increased thrombotic and infectious risk. Rituximab is a good option in non-immunocompromised patients, but long-term remissions are few. Eltrombopag and romiplostim have a good safety and efficacy profile, and have become a prominent drug in this subset, even if they are associated with a possible increased risk of thrombosis, and long-term toxicity is unknown. Other drugs, such as dapsone and danazol, have a well-known efficacy and safety profile, and still represent a valid option among elderly patients. Highlights • Special attention must be reserved for elderly patients with thrombocytopenia. • The diagnosis of primary ITP is challenging, mainly due to multiple comorbidities. • The increased risk of bleeding, thrombosis and infections impact treatment choice. • Steroids remain the first-line treatment, there is no consensus for subsequent line. • The balance between individual risks and benefits should drive treatment pathway. [ABSTRACT FROM AUTHOR]

Treatments for immune thrombocytopenic purpura (ITP) providing durable platelet responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 x 109/L or 50-150 x 109/L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 x 109/L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21 % and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial longterm clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making. [ABSTRACT FROM AUTHOR]