Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement
IMMUNOLOGIC RESEARCH
Authors: Quattrocchio, Giacomo; Barreca, Antonella; Demarchi, Andrea; Fenoglio, Roberta; Ferro, Michela; Del Vecchio, Giulio; Massara, Carlo; Rollino, Cristiana; Sciascia, Savino; Roccatello, Dario
Abstract
IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20(+) B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.
Incidence of CMV Replication and the Role of Letermovir Primary/Secondary Prophylaxis in the Early Phase After Allogeneic Hematopoietic Stem Cell Transplantation - A Single Centre Study
ANTICANCER RESEARCH
Authors: Studer, Ursina; Khanna, Nina; Leuzinger, Karoline; Hirsch, Hans H.; Heim, Dominik; Lengerke, Claudia; Tsakiris, Dimitrios A.; Halter, Joerg; Gerull, Sabine; Passweg, Jakob; Medinger, Michael; Gwerder, Malena
Abstract
Background/Aim: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. Patients and Methods: In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. Results: We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. Conclusion: Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.