P783 Clinical, Humanistic, and Economic Burden in Patients with PNH Receiving C5 Inhibition Treatment across UK, Germany, and France. Insights from the Commodore Burden of Illness Study

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disorder. In the UK, Germany, and France, C5 complement inhibitors, such as eculizumab and ravulizumab, both of which are intravenously (IV) infused, are the standard of care for PNH

Br J Haematol

International audienc

Allogreffe de cellules souches hématopoïétiques à conditionnement atténué dans le traitement des syndromes myélodysplasiques (étude rétrospective multicentrique de la SFGM-TC)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Reemergence of Splenectomy for ITP Second-line Treatment?

International audienceIntroduction: Corticosteroids are still the standard first-line treatment for immune thrombocytopenic purpura (ITP). As second-line therapy, splenectomy and Rituximab are both recommended. The aim of our study was to compare the efficacy of Rituximab to splenectomy in persistent or chronic ITP patients.Methods: Between January 1999 and March 2015, we retrospectively selected all consecutive patients who underwent an ITP second-line treatment: Rituximab or splenectomy. The distinction between open (OS) and laparoscopic splenectomy (LS) was analyzed. Primary outcome was composite: hospitalization for bleeding and/or thrombocytopenia and death from hemorrhage or infection. Secondary outcomes were based on response (R) and complete response (CR) rates as defined by the American Society of Hematology.Results: Ninety-six patients were included: 30 patients received Rituximab, 37 underwent OS, and 29 underwent LS. The follow-up was 30, 60, and 120 months in Rituximab, LS, and OS groups, respectively. At 30th month, the primary outcome-free survival rate was higher in splenectomy groups (84% for OS, 86% for LS) than Rituximab group (47%) (P = 0.0002). Similarly, at 30th month, R and CR rates were higher for OS (86.5% and 75.7%, respectively) and LS groups (93.1% and 89.7%) than Rituximab (46.7% and 30%) (P = 0.0001). Moreover, R rates remained elevated at 60th month for OS and LS groups (83.7% and 89.6% respectively) and 78.4% at 120th month for OS group.Conclusion: We observed that splenectomy for ITP second-line treatment was more effective than Rituximab regarding maintenance of R, CR, and overall response rates. OS and LS had similar efficacy

TAFRO Syndrome in Caucasians: A Case Report and Review of the Literature

TAFRO syndrome has been reported in Japan among human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman's disease (iMCD) patients. To date, the majority of iMCD patients with TAFRO syndrome originate from Japan

Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia

International audienceBackground We determined the safety, pharmacokinetics, pharmacodynamics, and antitumour activity of abexinostat in B-cell lymphoma or chronic lymphocytic leukaemia. Patients and methods Thirty-five patients received oral abexinostat 30, 45, or 60 mg/m(2) bid in a 3 + 3 design in three 21-day schedules: 14 days on treatment in schedule 1 (D1-14); 10 days in schedule 2 (D1-5 and D8-12); and 12 days in schedule 3 (D1-4, D8-11, and D15-18). Safety, tumour response, plasma concentration, and histone H3 acetylation were measured. Results Two dose-limiting toxicities occurred in each schedule (one grade 3 febrile neutropenia; five grade 4 thrombocytopenia) at 60 mg/m(2) bid (maximal tolerated dose). The recommended dose was 45 mg/m(2) bid; schedule 1 was considered optimal. Non-haematological drug-related toxicities included grade 1 or 2 diarrhoea (43%), nausea (23%), and vomiting (11%); haematological toxicities included thrombocytopenia (31% grade 3, and 26% grade 4), which remained manageable and reversible on withdrawal. Of 29 evaluable patients, there were 2 complete and 6 partial responses; median duration of response was 14.6 months (range 3-16.5 months) (1 cycle is equivalent to 0.75 months). There was no evidence for nonlinear pharmacokinetics. There was a correlation between dose and histone acetylation. Conclusion Abexinostat has manageable toxicity and induced some durable complete and partial responses in B-cell lymphoma or chronic lymphocytic leukaemia. Our results suggest most favourable responses in patients with follicular lymphoma, though further research would be needed to confirm this finding

Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of Primary Humoral Immunodeficiencies

BackgroundAn overall response assay [OVA, based on a 23-valent pneumococcal polysaccharide vaccine (PPV23)] is widely used to screen for anti-pneumococcal antibodies. Given the heterogeneity of response from one polysaccharide (PS) to another, a World Health Organization-standardized serotype-specific enzyme-linked immunosorbent assay (SSA) is considered to be the only reliable method for testing anti-PS antibody responses in individuals with suspected primary immunodeficiencies (PIDs).ObjectiveTo evaluate the OVA relative to the reference SSA.MethodsSerum samples of adult patients referred for a suspected PID were collected before and then 4–8 weeks after immunization with PPV23. The anti-pneumococcal response was systematically assessed with an SSA (7–16 serotypes) and interpreted according to the American Academy of Asthma, Allergy and Immunology’s current guidelines. We used receiver operating characteristic curves and agreement indices to assess the OVA’s diagnostic value in a first cohort. In order to validate these findings, a second (validation) cohort was then prospectively included.ResultsSixty-two adult patients were included, and 42 (67.7%) were defined as poor responders according to the SSA. Only the post-immunization titer in the OVA was able to correctly identify poor responders; a titer below 110 mg/L gave a positive predictive value of 100% [identifying 24 (57.1%) of the 42 poor responders], and similar levels of diagnostic performance were observed in the validation cohort. The pre-vaccination antibody titer, the post/pre-vaccination antibody titer ratio and a post-vaccination titer above 110 mg/L in the OVA were not predictive of the response in the SSA.ConclusionA post-vaccination antibody titer below 110 mg/L in the OVA was constantly associated with a poor PPV23 response using the SSA. In all other cases, SSA is the only reliable method for assessing diagnostic vaccination with PPV23