Optimizing the structure of interdisciplinary tumor boards for effective cancer care.

Introduction: Multi-professional interdisciplinary tumor boards (ITB) are essential institutions to discuss all newly diagnosed, relapsed or complex cancer patients in a team of specialists to find an optimal cancer care plan for each individual patient with regard to national and international clinical practice guidelines, patient´s preference and comorbidities. In a high-volume cancer center, entity-specific ITBs take place at least once a week discussing a large number of patients. To a high level of expertise and dedication, this also requires an enormous amount of time for physicians, cancer specialists and administrative support colleagues, especially for radiologists, pathologists, medical oncologists and radiation oncologists, who must attend all cancer-specific boards according to certification requirements. Methods: In this 15-month prospective German single-center analysis, we examined the established structures of 12 different cancer-specific ITBs at the certified Oncology Center and demonstrate tools helping to optimize processes before, during and after the boards for optimal, time-saving procedures. Results: By changing pathways, introducing revised registration protocols and new digital supports we could show that the workload of preparation by radiologists and pathologists could be reduced significantly by 22.9% (p=<0.0001) and 52.7% (p=<0.0001), respectively. Furthermore, two questions were added to all registration forms about the patient´s need for specialized palliative care support that should lead to more awareness and early integration of specialized help. Discussion: There are several ways to reduce the workload of all ITB team members while maintaining high quality recommendations and adherence to national and international guidelines.

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients.

Case Report: Acquired Haemophilia A Following mRNA-1273 Booster Vaccination Against SARS-CoV-2 With Concurrent Diagnosis of Pleomorphic Dermal Sarcoma.

While the global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still ongoing and new virus variants are emerging, there is a universal need for vaccines to protect individuals from severe complications and ideally control the pandemic by enabling herd immunity. Several vaccines against SARS-CoV-2 have been approved and are widely used to stem the recurring waves of coronavirus disease 2019 (COVID-19). Post-marketing surveillance is essential to record even rare safety issues related to these new vaccines. Among these issues, several autoimmune phenomena have been recorded in temporal association with and feasibly triggered by a vaccination. Acquired haemophilia A (AHA) is a rare condition characterized by new-onset haemorrhagic diathesis caused by an inhibitor of blood clotting factor VIII (FVIII), often in the elderly and most commonly associated with autoimmune or malignant disease. There have been a small number of AHA cases triggered by vaccinations, including those against SARS-CoV-2. We report the first case of AHA in temporal association with an mRNA-1273 booster vaccination. The diagnosis was made promptly, and the patient received appropriate care including immunosuppression using glucocorticoids, cyclophosphamide (CYC) and rituximab (RTX). The haemorrhage ceased after escalation of treatment, and the patient is recovering. Concurrent malignancy was initially ruled out using a wide scope of diagnostic tests, but pleomorphic dermal sarcoma (PDS) of the forehead occurred after initiation of specific AHA immunosuppressive treatment. Since large vaccination programs are ongoing worldwide and potential adverse events during post-marketing surveillance have been reported following vaccination against SARS-CoV-2, this case illustrates challenges in rare events occurring in association with SARS-CoV-2 vaccination and to proof a causal relationship. Therefore, there is an urgent need for reporting any events in association with SARS-CoV-2 vaccination, but also a crucial discussion about possible concurrent triggers and follow-up information about individual patients.

Patterns of Late Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with T-Cell Prolymphocytic Leukemia.

Initial treatment with the monoclonal anti-CD52 antibody alemtuzumab induces responses in the majority of patients with T-cell prolymphocytic leukemia (T-PLL). In eligible patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an option to consolidate hematological remissions. Here, we report our experience with 10 patients who received allo-HSCT against T-PLL. Notably, 3 patients with complete remission at transplantation and durable full-donor chimerism relapsed at months 12, 59, and 84 after transplantation, respectively. This relapse was associated with rapid progressive leukemia in 1 patient and extralymphatic lymphoma growth in the other 2. Despite CD52 positivity at relapse, alemtuzumab retreatment, donor lymphocyte infusions, and/or chemotherapy including salvage therapy, allo-HSCT yielded a transient partial response, only. Alemtuzumab induction and consolidative allo-HSCT enabled prolonged disease-free survival in these patients but failed to procure cure.

Loss of donor chimerism in remission after allogeneic stem cell transplantation of T-prolymphocytic leukemia patients following alemtuzumab induction therapy.

T-cell prolymphocytic leukemia is a rare aggressive malignancy with low susceptibility to conventional chemotherapy. The anti-CD52 antibody alemtuzumab induces remission, which requires consolidation by stem cell transplantation in eligible patients. In this case series, three chemotherapy-naïve T-PLL patients received alemtuzumab for remission induction and allogeneic SCT after reduced-intensity conditioning. While primary hematopoietic engraftment occurred in a timely fashion, donor chimerism declined in all patients between day 28 and day 290 post-transplantation. Loss of chimerism was not associated with disease recurrence, and full chimerisms were regained on donor leukocyte infusion. In six B-CLL patients, treated with identical regimens of alemtuzumab and SCT, a similar pattern of failing chimerism was not observed. We surmise that an accumulation of uncleared alemtuzumab in the plasma may impede the incoming graft after allogeneic SCT, which would indicate the need for close monitoring and management of engraftment to secure complete donor chimerism and putative cure in T-PLL patients.

Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms.

CONTEXT: Schizophrenia is the collective term for a heterogeneous group of mental disorders with a still obscure biological basis. In particular, the specific contribution of risk or candidate gene variants to the complex schizophrenic phenotype is largely unknown. OBJECTIVE: To prepare the ground for a novel "phenomics" approach, a unique schizophrenia patient database was established by GRAS (Göttingen Research Association for Schizophrenia), designed to allow association of genetic information with quantifiable phenotypes.Because synaptic dysfunction plays a key role in schizophrenia, the complexin 2 gene (CPLX2) was examined in the first phenotype-based genetic association study (PGAS) of GRAS [corrected] DESIGN: Subsequent to a classic case-control approach, we analyzed the contribution of CPLX2 polymorphisms to discrete cognitive domains within the schizophrenic population. To gain mechanistic insight into how certain CPLX2 variants influence gene expression and function, peripheral blood mononuclear cells of patients, Cplx -null mutant mice, and transfected cells were investigated. SETTING: Coordinating research center (Max Planck Institute of Experimental Medicine) and 23 collaborating psychiatric centers all over Germany. PARTICIPANTS: One thousand seventy-one patients with schizophrenia (DSM-IV) examined by an invariant investigator team, resulting in the GRAS database with more than 3000 phenotypic data points per patient, and 1079 healthy control subjects of comparable ethnicity. Main Outcome Measure Cognitive performance including executive functioning, reasoning, and verbal learning/memory. RESULTS: Six single-nucleotide polymorphisms, distributed over the whole CPLX2 gene, were found to be highly associated with current cognition of schizophrenic subjects but only marginally with premorbid intelligence. Correspondingly, in Cplx2 -null mutant mice, prominent cognitive loss of function was obtained only in combination with a minor brain lesion applied during puberty, modeling a clinically relevant environmental risk ("second hit") for schizophrenia. In the human CPLX2 gene, 1 of the identified 6 cognition-relevant single-nucleotide polymorphisms, rs3822674 in the 3' untranslated region, was detected to influence microRNA-498 binding and gene expression. The same marker was associated with differential expression of CPLX2 in peripheral blood mononuclear cells. CONCLUSIONS: The PGAS allows identification of marker-associated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression.