Comparison of two autologous hematopoietic stem cell mobilization strategies in patients with multiple myeloma: CE plus G-CSF versus G-CSF only: A single-center retrospective analysis.

Background: Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system.

The role of extended coagulation screening in adult cranial neurosurgery.

Introduction: Postoperative hemorrhage after adult cranial neurosurgery is a serious complication with substantial morbidity and mortality.

Research Question: We investigated if an extended preoperative screening and an early treatment of previously undetected coagulopathies may decrease the risk of postoperative hemorrhage.

Methods: A prospective study cohort of patients undergoing elective cranial surgery and receiving the extended coagulatory work-up were compared to a propensity matched historical control cohort.

Advanced Therapy Medicinal Products and the Changing Role of Academia.

Academic institutions coin the ATMP landscape but do not possess an industry-like capacity to vigorously pursue the full developmental pathway to marketing authorization. At the same time, industry has fostered clinical trials with ATMPs, brought the first products to marketing authorization, and defined novel modes of interaction with academia. A regulatory niche for local manufacturing of ATMPs within an academic institution had been foreseen in Regulation (EU) 1394/2007 under the term "Hospital Exemption" but remained ill-defined.

Emergency Use of Convalescent Plasma: Perception of the Regulatory Framework from a Clinical Perspective.

The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty.

[Update 2021: COVID-19 from the Perspective of Haematology and Haemostaseology].

Infection with SARS-CoV-2 has a profound influence on the hematopoetic system that mediates clinical symptoms and mortality. Several studies have shown that treatment of the cytokine storm (CRS) with anti-inflammatory drugs like dexamethasone and tocilizumab can significantly improve survival. Systematic reviews confirm the safety of convalescent plasma administration and offer initial indications of its effectiveness in certain groups.

ABO subgroup incompatibility with severe hemolysis after consecutive allogeneic stem cell transplantations.

Allogeneic hematopoietic stem cell transplantations (HSCTs) represent a curative strategy for treating hematologic malignancies yet bear dangerous and frequently life-threatening complications including the development of graft-versus-host disease. Here, we present a case of a patient that suffered from relapsed/refractory multiple myeloma, a hematologic neoplasm characterized by clonal proliferation of malignant plasma cells in the bone marrow. During the course of his disease, the patient underwent consecutive allogeneic HSCTs, during which he developed a clinical meaningful and hitherto unreported ABO subgroup incompatibility, leading to persistent hemolysis.

Targeted Natural Killer Cell-Based Adoptive Immunotherapy for the Treatment of Patients with NSCLC after Radiochemotherapy: A Randomized Phase II Clinical Trial.

Purpose: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells.

[COVID-19 from the Perspective of Haematology and Haemostaseology].

Infection with SARS-COV-2 leads to a number of pathologies in the hematopoetic system that have significant impact on clinical symptoms and mortality. There are 3 stages of infection: (1) early upper respiratory tract infection with fever and lymphopenia (2) pulmonary phase and (3) hyperinflammatory phase with the clinical signs of organ failure such as ARDS/shock. Hyperinflammation, which is triggered by activation of T cells and monocytes/macrophages, is essential for organ pathologies.

Horses for courses: an approach to the qualification of clinical trial sites and investigators in ATMPs.

The advanced therapy medicinal products (ATMPs) landscape is entirely different from classical drug development. Academia has been the major source of ATMP development, and academic hospitals act as trial sites for the clinical testing of ATMPs, including early academic-led trials as well as industry-sponsored trials that pursue the full developmental pathway to market authorization. The recent breakthrough developments in some ATMPs, such as genetically engineered immune cells, have confronted academic hospitals with a substantial amount of public demand, competitive pressure, and costs.

Targeted in-vitro-stimulation reveals highly proliferative multi-virus-specific human central memory T cells as candidates for prophylactic T cell therapy.

Adoptive T cell therapy (ACT) has become a treatment option for viral reactivations in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Animal models have shown that pathogen-specific central memory T cells (TCM) are protective even at low numbers and show long-term survival, extensive proliferation and high plasticity after adoptive transfer. Concomitantly, our own recent clinical data demonstrate that minimal doses of purified (not in-vitro- expanded) human CMV epitope-specific T cells can be sufficient to clear viremia.

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study.

Background: Membrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as a tumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) and Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, and programmed death(PD)-1 inhibition were combined to improve the efficacy of tumor-specific immune cells in a non-small cell lung carcinoma (NSCLC) patient.

Patient: Following simultaneous RCT (64.

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low.

Development of cell therapy medicinal products by academic institutes.

In the rapidly evolving fields of cellular immunotherapy, gene therapy and regenerative medicine, a wide range of promising cell therapy medicinal products are in clinical development. Most products originate from academic research and are explored in early exploratory clinical trials. However, the success rate toward approval for regular patient care is disappointingly low.

Immunotherapy: opportunities, risks and future perspectives.

This review is intended to reflect upon the current status and perspectives of cell-based immunotherapy at a time when the promise of extensive pre-clinical research has been translated into encouraging clinical responses. However, some of these have also been complicated by significant adverse reactions. As the field moves towards definitive late stage trials, with a growing interest from pharmaceutical companies, we realize that novel cell therapy strategies pose questions that are familiar to traditional drug development, along with new considerations due to the potential of T cells to persist long term and to expand after adoptive transfer.

Drug-induced agranulocytosis in the Berlin case-control surveillance study.

Purpose: Drug-induced agranulocytosis (DIAG) is a rare but serious adverse drug reaction. The Berlin Case-Control Surveillance Study (FAKOS) aimed to identify pharmaceuticals with an increased risk for this condition.

Methods: Adult patients with acute non-chemotherapy-induced agranulocytosis, developed in hospital or in the outpatient setting, were ascertained by active surveillance in all 51 Berlin hospitals between the years 2000 and 2010.

Regulation of advanced therapy medicinal products in Europe and the role of academia.

Background Aims: Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them.

Joint conference on the impact of EU legislation on therapeutic advance.

On October 11, 2012, two FP7-funded Research Consortia, CONTRACT (Consent in a Trial and Care Environment) and Academic GMP, held a Joint Conference in Brussels entitled "The Impact of EU Legislation on Therapeutic Advance." Academic researchers including stem cell transplant physicians and cell therapy specialists, legal advocates and representatives from industry, regulatory authorities and patient advocacy groups met with members of the European Parliament and the European Commission. This article summarizes important points of discussion and detailed proposals for improvement.