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Purpose: Multiple myeloma (MM) is a severe hemato-oncological disease with high mortality and increasing incidence rate. Since evidence on exercise therapy in MM patients remains limited, this study examines feasibility, adherence, and efficacy based on real-life data from an oncologic care structure. Methods: A data evaluation of MM patients who participated in the oncologic exercise and movement therapy (OTT) at the Cologne University Hospital between 2012 and 2019 was conducted. The patient flow was incrementally reduced to four cohorts, intention-to-treat cohort (ITTC), safety cohort (SC), adherence cohort (AC), and efficacy cohort (EC). Cohorts were evaluated descriptively and by means of correlation analysis as well as group and time comparisons. Results: Thirty patients registered at the OTT between 2012 and 2019 (ITTC). The SC (N = 26) attended exercise therapy on average about one session per week over a period of 8 months. One-third dropped out within 3 months. In the AC (N = 15), BMI at baseline exhibited a strong and very significant negative correlation with exercise adherence. In the EC (N = 8), a significant improvement in physical functioning and a tendency towards significance in fatigue reduction between two measurement points was observed. No adverse events were documented. Conclusions: The present observatory study reveals safety and feasibility while indicating adherence and efficacy of exercising MM patients under real-life therapy circumstances. Found obstacles to exercising as well as improvements in questionnaire scale scores need to be further examined in confirmatory study designs. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019.Methods: We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES).Results: After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection.Conclusions: The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing. [ABSTRACT FROM AUTHOR]

Acquired immunoglobulin G (IgG)-mediated thrombotic thrombocytopenic purpura ( TTP) has not yet been described in non-twin siblings. We report two cases of acquired TTP in Caucasian sisters with inactive ADAMTS13 metalloprotease due to ADAMTS13 autoantibodies suggesting a role of genetic determinants in this life-threatening disease. However, human leucocyte antigen ( HLA) class II types presumably associated with acquired TTP were not identified in the patients, indicating that HLA class II typing may not be useful in acquired TTP risk assessment of family members. [ABSTRACT FROM AUTHOR]

Rationale: Steroid refractory graft‐vs‐host disease (sr‐GvHD) represents a challenging complication after allogeneic hematopoietic cell transplantation (allo‐HCT). Intestinal microbiota (IM) diversity and dysbiosis were identified as influencing factors for the development of acute GvHD. Fecal microbiota transfer (FMT) is hypothesized to restore IM dysbiosis, but there is limited knowledge about the significance of FMT in the treatment of sr‐GvHD. Objectives: We studied the effects of FMT on sr‐GvHD in allo‐HCT patients from two German tertiary clinical centers (n = 11 patients; period: March 2017 until July 2019). To assess safety and clinical efficacy, we analyzed clinical data pre‐ and post‐FMT (day ‐14 to +30 relative to FMT). Moreover, IM were analyzed in donor samples and in a subset of patients pre‐ and post‐FMT by 16S rRNA sequencing. Results: Post‐FMT, we observed no intervention‐associated, systemic inflammatory responses and only minor side effects (5/11 patients: abdominal pain and transformation of peristalsis—each 3/11 and vomiting—1/11). Stool frequencies and volumes were significantly reduced [pre‐ vs post‐FMT (d14): P <.05, respectively] as well as clear attenuation regarding both grading and staging of sr‐GvHD was present upon FMT. Moreover, IM analyses revealed an increase of alpha diversity as well as a compositional shifts toward the donor post‐FMT. Conclusions: In our study, we observed positive effects on sr‐GVHD after FMT without the occurrence of major adverse events. Although these findings are in line with published data on beneficial effects of FMT in sr‐GvHD, further randomized clinical studies are urgently needed to better define the clinical validity including mode of action. [ABSTRACT FROM AUTHOR]

Patients undergoing allogeneic stem cell transplantation (allo-SCT) are given a real chance of cure, but at the same time are confronted with a considerable risk of mortality and of severe long-term impediments. This narrative, non-systematic literature review aims to describe the supportive and palliative care needs of allo-SCT recipients, including long-term survivors or those relapsing or dying after transplantation. It also evaluates the feasibility and effectivity of integrating palliative care early in transplant procedures. In this appraisal of available literature, the main findings relate to symptoms like fatigue and psychological distress, which appear to be very common in the whole allo-SCT trajectory and might even persist many years post-transplantation. Chronic GvHD has a major negative impact on quality of life. Overall, there is a paucity of research on further issues in the context of allo-SCT, like the distress related to the frequently unpredictable post-transplant trajectory and prognosis, as well as the end-of-life phase. First randomized controlled results support the effectiveness of early integration of specialized palliative care expertise into transplant algorithms. Barriers to this implementation are discussed. [ABSTRACT FROM AUTHOR]

Objective: Fluconazole or posaconazole is a standard of care in antifungal prophylaxis for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). However, many patients need to interrupt standard prophylaxis due to intolerability, drug‐drug interactions, or toxicity. Micafungin has come to prominence for these patients. However, the optimal biological dose of micafungin stays unclear. Methods: We retrospectively evaluated the efficacy of micafungin as antifungal prophylaxis in HSCT patients. Micafungin was applied as bridging in patients who were not eligible to receive oral posaconazole. Micafungin was either given at a dose of 100 mg or 50 mg SID. Results: A total of 173 patients received micafungin prophylaxis, 62 in the 100 mg and 111 in the 50 mg dose group. The incidence of probable or proven breakthrough IFDs during the observation period was one in the 100 mg and one in the 50 mg group. Fungal‐free survival after 100 days was 98% and 99% (P =.842), and overall survival after 365 days was 60% and 63% (P =.8) respectively. In both groups, micafungin was well tolerated with no grade 3 or 4 toxicities. Conclusion: In this retrospective analysis, which was not powered to detect non‐inferiority, micafungin is effective and complements posaconazole as fungal prophylaxis in HSCT. [ABSTRACT FROM AUTHOR]

The article reports on a study which investigated the impact of telomere length on the outcome of allogeneic stem cell transplantation (SCT) for patients with poor risk chronic lymphocytic leukaemia (CLL) based on the German CLL3X trial which included 100 patients. Topics covered include association of telomere length with clinical characteristics, and analysis of telomere length using quantitative polymerase chain reaction.

Background Intravenous bridging strategies increase exposure of antifungal prophylaxis in high-risk hematological patients. The cost-effectiveness of such strategies has not been analyzed. Methods A recent study compared the impact of oral posaconazole ( POS) and oral posaconazole with intravenous micafungin bridging ( POS- MIC) as prophylactic antifungal regimens in patients undergoing allogeneic stem cell transplantation (a SCT). Based on data from the Cologne Cohort of Neutropenic Patients ( Co Co Nut), a health economic evaluation of direct treatment costs was performed to analyze the economic impact of micafungin bridging. Analysis was undertaken based on current guidelines for the German societal perspective with an annual discount rate of 5%, whereby indirect costs were disregarded due to the severity of the underlying disease. Sensitivity analysis of cost calculation with different discount rates was performed to improve robustness of our health economic evaluation. Results A retrospective case-control analysis of patients undergoing a SCT between 05/2006 and 07/2011 was performed; 106 patients each in the POS and POS- MIC group were included. In the POS and POS- MIC group, mean costs per patient for the treatment on bone marrow transplant ward were €27 228 (95% CI: €24 932-€29 525) vs. €27 894 (95% CI: €26 414-€29 375; P = 0.629), for diagnostic measures €2124 (95% CI: €1823-€2425) vs. €1269 (95% CI: €1168-€1370; P ≤ 0.001), for laboratory findings €10 612 (95% CI: €9681-€11 544) vs. €8836 (95% CI: €8198-€9475; P = 0.002), and for overall antifungal treatment €6105 (95% CI: €4703-€7508) vs. €6943 (95% CI: €5393-€8493; P = 0.428), resulting in mean overall costs per patient of €60 304 (95% CI: €53 969-€66 639) vs. €58 089 (95% CI: €51 736-64 442; P = 0.625). Conclusions Our health economic evaluation shows micafungin bridging in a SCT patients did not result in excess cost. Higher acquisition costs of antifungal prophylaxis were balanced by a reduced incidence of possible IFD and lower costs for empirical, preemptive, and targeted antifungal therapy as well as lower costs for diagnostic measures and laboratory tests in the micafungin bridging group. [ABSTRACT FROM AUTHOR]

Brentuximab vedotin has emerged as a possible treatment option in patients suffering from relapsed and refractory Hodgkin lymphoma (HL). We investigated the role of 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for monitoring treatment response to brentuximab vedotin in patients with relapsed and refractory HL. Twelve consecutive, heavily pretreated patients with relapsed and refractory HL treated with brentuximab vedotin were available for analysis. FDG-PET/CT studies were performed early during treatment after a median of 3 cycles (range, 2-5 cycles), and were analyzed visually using a 5-point scale (5PS) and quantitatively using the maximum standardized uptake value (SUVmax) and the three-dimensional (3D) isocontour at 50% of the maximum pixel value (SUV50) in the hottest single lesion. The median follow-up in our study cohort was 16 months (range, 5-30 months). The median progression-free survival (PFS) was 12.5 months and PFS at 12 months was 58%. Patients treated with brentuximab vedotin and negative interim FDG-PET/CT assessed by visual or quantitative analysis demonstrated a significantly prolonged PFS compared to patients with positive interim FDG-PET/CT. The 1-year PFS was 100% in patients with negative interim FDG-PET/CT assessed by visual analysis, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 38% ( p = 0.033). The 1-year PFS was 75% in patients with negative interim FDG-PET/CT assessed by quantitative analysis using the SUV50, whereas patients with positive interim FDG-PET/CT had a worse outcome with a 1-year PFS of 25% ( p = 0.017) Interim FDG-PET/CT might be a suitable diagnostic approach to predict response to brentuximab vedotin in relapsed and refractory HL. [ABSTRACT FROM AUTHOR]

Introduction: In patients with chronic myeloid leukemia, tyrosine kinase inhibitors suppress the BCR-ABL+ clone and often induce complete molecular remissions. Megakaryocytes in such patients have been shown to be derived from the BCR-ABL+ clone, and abnormal platelet function is frequent in chronic myeloid leukemia. However, little is known about the influence of modern targeted therapy on chronic myeloid leukemia-associated platelet disorders.Case Presentation: We report the case of a massive hemorrhage in a 32-year-old Caucasian man caused by chronic myeloid leukemia-associated platelet dysfunction, which improved after treatment with imatinib.Conclusion: This report demonstrates that platelet dysfunction and bleeding disorder in BCR-ABL+ chronic myeloid leukemia can successfully be treated with imatinib. We suggest the monitoring of platelet function in future studies using imatinib to treat patients with chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

Objective: To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods: We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling ( n = 18) or unrelated ( n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan ( n = 25) or total-body irradiation ( n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results: The incidence of grades II–IV and III–IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age ≥40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion: These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality. [ABSTRACT FROM AUTHOR]

Patients with primary progressive or refractory Hodgkin’s disease (HD) or aggressive non-Hodgkin’s lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18–55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m2) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (990 mg/m2). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m2), etoposide (1200 mg/m2), cytarabine (1600 mg/m2), and melphalan (140 mg/m2). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients who have been treated with an allogeneic, hematopoietic stem cell transplantation can develop severe graft-versus-host disease. This complication may place patients in a life-threatening situation, in which a curative goal of care can no longer be achieved and needs to be changed into a palliative one. In our clinical experience, this patient group is very heterogenous, with a high disease burden and special needs that are often overlooked. In this review, we summarize the current literature on the needs and burdens of patients with severe forms of graft-versus-host disease from a supportive and palliative care perspective to draw a comprehensive picture of this patient group. Despite a fundamental lack of studies, the findings suggest that the more severe the GvHD, the worse the quality of life and physical functioning. The relative void of data highlights the need for research on this special issue in order to optimize the treatment and care of patients with severe graft-versus-host disease. Graft-versus-host disease (GvHD) is a frequent, and often life-threatening, complication after an allogeneic, hematopoietic stem cell transplantation (allo-SCT). It can appear in an acute or a chronic form and presents different grades of severity. Particularly, the severe forms of GvHD are often responsible for a change of the curative intent for allo-SCT into a palliative goal of care. For this non-systematic review, we conducted a focused literature search in the MEDLINE database via PubMed to examine whether patients with severe forms of GvHD might have special needs and burdens from a supportive and palliative care perspective. To draw a comprehensive picture of this patient group, we included findings on quality of life (QoL) and physical symptoms and function as well as psychological and spiritual well-being. In most domains, patients with severe forms of GvHD showed greater impairment and a higher symptom burden compared to patients with milder forms of GvHD. However, we could not identify any studies that specifically investigated patients with severe forms of GvHD. Further research in this field is necessary to guarantee the highest standard of care for this very special patient group. [ABSTRACT FROM AUTHOR]

The neuropeptide CGRP, acting through the G-protein coupled receptor CALCRL and its coreceptor RAMP1, plays a key role in migraines, which has led to the clinical development of several inhibitory compounds. Recently, high CALCRL expression has been shown to be associated with a poor prognosis in acute myeloid leukemia (AML). We investigate, therefore, the functional role of the CGRP-CALCRL axis in AML. To this end, in silico analyses, human AML cell lines, primary patient samples, and a C57BL/6-based mouse model of AML are used. We find that CALCRL is up-regulated at relapse of AML, in leukemic stem cells (LSCs) versus bulk leukemic cells, and in LSCs versus normal hematopoietic stem cells. CGRP protects receptor-positive AML cell lines and primary AML samples from apoptosis induced by cytostatic drugs used in AML therapy, and this effect is inhibited by specific antagonists. Furthermore, the CGRP antagonist olcegepant increases differentiation and reduces the leukemic burden as well as key stem cell properties in a mouse model of AML. These data provide a basis for further investigations into a possible role of CGRP-CALCRL inhibition in the therapy of AML. [ABSTRACT FROM AUTHOR]

Background: Personalized and risk-adapted treatment strategies in multiple myeloma prerequisite feasibility of prospective assessment, reporting of targets, and prediction of survival probability in clinical routine. Our aim was first to set up and prospectively test our experimental and analysis strategy to perform advanced molecular diagnostics, i.e., interphase fluorescence in-situ hybridization (iFISH) in ≥ 90% and gene expression profiling (GEP) in ≥ 80% of patients within the first cycle of induction chemotherapy in a phase III trial, seen as prerequisite for target expression-based personalized treatment strategies. Secondly, whether the assessment of risk based on the integration of clinical, cytogenetic, and expression-based parameters ("metascoring") is possible in this setting and superior to the use of single prognostic factors. Methods: We prospectively performed plasma cell purification, GEP using DNA-microarrays, and iFISH within our randomized multicenter GMMG-MM5-trial recruiting 604 patients between July 2010 and November 2013. Patient data were analyzed using our published gene expression report (GEP-R): after quality and identity control, integrated risk assessment (HM metascore) and targets were reported in clinical routine as pdf-document. Results: Bone marrow aspirates were obtained from 573/604 patients (95%) and could be CD138-purified in 559/573 (97.6%). Of these, iFISH-analysis was possible in 556 (99.5%), GEP in 458 (82%). Identity control using predictors for sex, light and heavy chain type allowed the exclusion of potential sample interchanges (none occurred). All samples passed quality control. As exemplary targets, IGF1R-expression was reported expressed in 33.1%, AURKA in 43.2% of patients. Risk stratification using an integrated approach, i.e., HM metascore, delineated 10/77/13% of patients as high/medium/low risk, transmitting into significantly different median progression-free survival (PFS) of 15 vs. 39 months vs. not reached (NR; P < 0.001) and median overall survival (OS) of 41 months vs. NR vs. NR (P < 0.001). Five-year PFS and OS-rates were 5/31/54% and 25/68/98%, respectively. Survival prediction by HM metascore (Brier score 0.132, P < 0.001) is superior compared with the current gold standard, i.e., revised ISS score (0.137, P = 0.005). Conclusions: Prospective assessment and reporting of targets and risk by GEP-R in clinical routine are feasible in ≥ 80% of patients within the first cycle of induction chemotherapy, simultaneously allowing superior survival prediction. [ABSTRACT FROM AUTHOR]