Publications by authors named "Lorenz Thurner"

We report here on a patient with concomitant indolent lymphoma who showed a rapid progressive deterioration of his general condition and emerging neurological symptoms. The combination of severe B symptoms with hypermetabolic involvement of the adrenal glands and multiple central nervous system (CNS) lesions initially suggested a malignant disease. However, when the patient presented to us with biopsy results from one of the CNS lesions, the biopsy revealed granulomatous inflammation but no evidence of malignancy.

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Cytomegalovirus (CMV) reactivation after stem cell or solid organ transplantation remains a major cause of morbidity and mortality in this setting. T-cell receptor (TCR)-like antibodies bind to intracellular peptides presented in major histocompatibility complex (MHC) molecules on the cell surface and may have the potential to replace T-cell function in immunocompromised patients. Three previously selected CMV-specific, human leukocyte antigen (HLA)-restricted (HLA-A*0101, HLA-A*0201 and HLA-B*0702) Fab-antibodies (A6, C1 and C7) were produced as IgG antibodies with Fc optimization.

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Article Synopsis
  • Glofitamab, a bispecific antibody targeting CD20 and CD3, shows promise for treating relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in heavily pretreated patients, with an overall response rate of 47%.
  • In a study involving 70 patients in Germany, Austria, and Switzerland, the median number of prior treatments was four, with notable safety concerns including cytokine release syndrome in 40% of cases.
  • Important findings indicate that elevated LDH levels predict poorer outcomes, and recent treatment with bendamustine may reduce the efficacy of glofitamab, suggesting careful treatment sequencing is essential.
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Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and multiple myeloma have poor outcomes. CAR-T completely changed the landscape of therapy options, improving not only response rates but also survival outcomes. Hematological toxicity after chimeric antigen receptor therapy (CAR-T) is of increasing interest, being a recognized prognostic factor in this setting.

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Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT).

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Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes.

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Objective: Psoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso).

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Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN.

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Donor-specific anti-human leukocyte antigen (HLA) antibodies represent a main cause of primary graft failure specifically in the setting of haploidentical stem cell transplantation. Newer therapy strategies including daratumumab could overcome some of these limitations. We describe the case of a patient with refractory acute myeloid leukemia.

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Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019.

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Article Synopsis
  • MICA polymorphisms are linked to higher rates of acute GvHD and poor outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), with MICB's role still being unclear.
  • Researchers analyzed a large cohort for MICB polymorphisms, assessing how MICB matching affects outcomes after unrelated HSCT, finding that 69.2% were 10/10 HLA matched.
  • In the 9/10 HLA matched group, MICB mismatches led to worse disease-free survival and relapse-free survival, while MICA mismatches did not significantly impact outcomes, suggesting MICB typing might aid in donor selection among 9/10 matched donors.
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Primary vitreoretinal lymphoma (PVRL) is a rare subtype of DLBCL and can progress into primary central nervous system lymphoma (PCNSL). To investigate the role of chronic antigenic stimulation in PVRL, we cloned and expressed B-cell receptors (BCR) from PVRL patients and tested for binding against human auto-antigens. SEL1L3, a protein with multiple glycosylation sites, was identified as the BCR target in 3/20 PVRL cases.

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Background: Adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) resemble a continuum of a rare, polygenic IL-1β-driven disease of unknown etiology.

Objective: In the present study we sought to investigate a potential role of recently described autoantibodies neutralizing the interleukin-1(IL-1)-receptor antagonist (IL-1-Ra) in the pathogenesis of Still's disease.

Methods: Serum or plasma samples from Still's disease patients (AOSD, n = 23; sJIA, n = 40) and autoimmune and/or inflammatory disease controls (n = 478) were analyzed for autoantibodies against progranulin (PGRN), IL-1Ra, IL-18 binding protein (IL-18BP), and IL-36Ra, as well as circulating IL-1Ra and IL-36Ra levels by ELISA.

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Article Synopsis
  • * A study involving 1439 acute leukemia patients showed that 6% had a prior history of IA before receiving alloSCT, resulting in higher non-relapse mortality (17.3% for those with IA compared to 11.2% for those without), and poorer outcomes in terms of relapse-free and overall survival rates.
  • * Despite the challenges linked to pre-SCT IA, over two-thirds of patients with this condition were alive one
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Article Synopsis
  • - Patients with diffuse large cell lymphoma have better outcomes from rituximab immuno-chemotherapy when they have adequate vitamin D levels, particularly among women.
  • - A study on vitamin D supplementation showed that NK cells had increased expression of several IFN-α subtypes after reaching sufficient vitamin D levels, enhancing their cytotoxic abilities.
  • - While some pathways related to cytokine production and certain genes were downregulated post-supplementation, the increase in IFN-α expression helps explain the improved immune response in patients with adequate vitamin D.
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Purpose: Blood culture (BC) diagnostics are influenced by many factors. We performed a targeted interdisciplinary analysis to analyse effects of various measures on BC diagnostics performance.

Methods: A diagnostic stewardship initiative was conducted at two intervention and two control wards in a German tertiary level hospital.

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UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation.

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UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans.

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Previous studies have illustrated associations between the presence of activating killer cell immunoglobulin-like receptor (KIR) genes and lower susceptibility to hematologic malignancies in humans. In addition, favorable hematopoietic stem cell transplantation (HSCT) outcomes have been reported in patients who received transplants from donors with KIR genotypes dominant for activating KIR receptors. However, the association of activating KIR genes on an allelic level with disease and their impact on HSCT outcome has been little investigated to date.

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Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses.

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Light chain amyloidosis (AL) is one of the most common forms of systemic amyloidosis and is caused by the deposition of insoluble fibrils derived from misfolded and aggregated immunoglobulin light chains (LC). To uncover the causes leading to this aggregation, we compared AL LC sequences with those of patients with the related disease multiple myeloma (MM), which do not aggregate in insoluble fibrils in vivo. IGLV2-14 is one of the most common AL-associated IGLV subfamilies.

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Background: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy.

Methods: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .

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Despite recent advances in the therapy of diffuse large B-cell lymphoma, not otherwise specified (DLBCL), around 30% of patients develop refractory disease or relapse after first-line treatment. Recently, Ars2 was reported as the auto-antigenic target of the B-cell receptor (BCR) in approximately 25% of activated B-cell DLBCL cases. Ars2 could be used to specifically target B cells expressing Ars2-reactive BCRs.

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