Low Graft Invariant Natural Killer T-Cell Dose Is a Risk Factor for Cytomegalovirus Reactivation After Allogeneic Hematopoietic Cell Transplantation.

Cytomegalovirus (CMV) reactivation is common after allogeneic hematopoietic cell transplantation (HCT) and may result in fatal CMV disease. Invariant natural killer T (iNKT) cells are potent modulators of the immune system preventing graft-versus-host disease while promoting graft-versus-leukemia effects. It is thought that iNKT cells selectively influence mediators of both innate and adaptive immunity.

Cooperating, congenital neutropenia-associated Csf3r and Runx1 mutations activate pro-inflammatory signaling and inhibit myeloid differentiation of mouse HSPCs.

Patients with the pre-leukemia bone marrow failure syndrome called severe congenital neutropenia (CN) have an approximately 15% risk of developing acute myeloid leukemia (AML; called here CN/AML). Most CN/AML patients co-acquire CSF3R and RUNX1 mutations, which play cooperative roles in the development of AML. To establish an in vitro model of leukemogenesis, we utilized bone marrow lin cells from transgenic C57BL/6-d715 Csf3r mice expressing a CN patient-mimicking truncated CSF3R mutation.

Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation.

We aimed to evaluate the determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) and to describe factors predicting the main post-HCT complications. This retrospective study by the European Society for Blood and Marrow Transplantation included 2916 myelofibrosis patients who underwent first allo-HCT from an HLA-identical sibling or unrelated donor between 2000 and 2016. After a median follow-up of 4.

Cryobiopsy increases the EGFR detection rate in non-small cell lung cancer.

Objectives: Detection of activating epidermal growth factor receptor (EGFR) mutation is crucial for individualized treatment of advanced non-small-cell lung cancer (NSCLC). However little is known about how biopsy technique affects the detection rate of EGFR mutations. This retrospective, single center study evaluated the detection rate of EGFR mutations in tissue obtained by bronchoscopic cryobiopsy and compared this to other standard tissue sampling techniques.

Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party.

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult systemic sclerosis patients undergoing a first autologous hematopoietic stem cell transplantation between December 2012 and February 2016 were prospectively included in the study.

Outcome after autologous stem cell transplantation in primary refractory or relapsed Hodgkin lymphoma-a long-term follow-up single center experience.

Autologous stem cell transplantation (autoSCT) can achieve long-term remission in primary refractory or relapsed Hodgkin lymphoma (r/r HL); however, still up to 50% of patients relapse after autoSCT. In this retrospective analysis, we investigated the impact of autologous stem cell transplantation in a consecutive, unselected cohort of primary refractory and relapsed Hodgkin lymphoma patients (n = 66) with the majority of patients treated in the pre-brentuximab vedotin and immune checkpoint inhibitor era. In our cohort, a 5-year overall survival (OS) from autoSCT of 59.

Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial.

Purpose: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance.

Patients And Methods: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression.

Invariant natural killer T cells are functionally impaired in patients with systemic sclerosis.

Background: Systemic sclerosis (SSc) is a potentially fatal autoimmune disease that leads to extensive fibrosis of the skin and internal organs. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes being able to orchestrate dysregulated immune responses. The purpose of this study was to evaluate numbers and function of iNKT cells in patients with SSc and to analyze their correlation with disease parameters.

Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma.

Background And Objectives: In patients with multiple myeloma (MM), unexpected bleeding complications remain a major issue. Since routine coagulation parameters are often inconspicuous, diagnosis and treatment of the underlying coagulation disorders are challenging.

Patients And Methods: In our single-center observational study, we analyzed 164 patients with MM for coagulation disorders and bleeding complications.

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis.

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199).

The role of autologous stem cell transplantation in peripheral T cell lymphoma: a long-term follow-up single-center experience.

Purpose: Peripheral T cell lymphomas (PTCL) are a rare and heterogeneous group of aggressive non-Hodgkin lymphomas, showing a generally poor prognosis. In this retrospective analysis, we aimed to investigate the impact of autologous stem cell transplantation (autoSCT) in PTCL.

Methods: A retrospective analysis of 58 consecutive unselected PTCL patients aged 21-71 years undergoing autoSCT as first-line consolidation as well as in the relapse setting was performed.

The German National Registry of Primary Immunodeficiencies (2012-2017).

The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.

Publisher Correction: Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote Lysis of Leukemic Blasts in a CD1d-Dependent Manner.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects.

Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.

Retrospective single center analysis of outcome, risk factors and therapy in steroid refractory graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Acute and chronic graft-vs.-host disease (aGvHD and cGvHD) are major complications after allogeneic hematopoietic cell transplantation (HCT) leading to substantial morbidity and mortality. This retrospective single-center study analyzes incidence, therapy, and outcome of GvHD in n = 721 patients ≥18 years having received allogeneic HCT 2004-2013 with a special focus on steroid refractory GvHD.

Comparison of Dynamic International Prognostic Scoring System and MYelofibrosis SECondary to PV and ET Prognostic Model for Prediction of Outcome in Polycythemia Vera and Essential Thrombocythemia Myelofibrosis after Allogeneic Stem Cell Transplantation.

We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .

G-CSF administration prior to donor lymphocyte apheresis promotes anti-leukaemic effects in allogeneic HCT patients.

Donor lymphocyte infusion (DLI) is an effective method to establish full donor chimerism or to prevent and treat relapse after allogeneic haematopoietic cell transplantation (allo-HCT). Usually, DLIs are collected from naïve donors as steady-state lymphocytes. When donor lymphocytes are collected during stem cell apheresis, donors are pre-treated with granulocyte colony-stimulating factor (G-CSF).

Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation.

The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model.

Human iPSC-based model of severe congenital neutropenia reveals elevated UPR and DNA damage in CD34 cells preceding leukemic transformation.

We describe the establishment of an embryoid-body-based protocol for hematopoietic/myeloid differentiation of human induced pluripotent stem cells that allows the generation of CD34 cells or mature myeloid cells in vitro. Using this model, we were able to recapitulate the defective granulocytic differentiation in patients with severe congenital neutropenia (CN), an inherited preleukemia bone marrow failure syndrome. Importantly, in vitro maturation arrest of granulopoiesis was associated with an elevated unfolded protein response (UPR) and enhanced expression of the cell cycle inhibitor p21.

Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) can be defined as a clonal expansion of B cells with stereotypic BCRs. Somatic hypermutation of the BCR heavy chains (IGVH) defines a subgroup of patients with a better prognosis. In up to 10% of CLL cases, a transformation to an aggressive B cell lymphoma (Richter's syndrome) with a dismal prognosis can be observed over time.