Safety and cost effectiveness of outpatient autologous hematopoietic stem cell transplantation for multiple myeloma — single-center experience of a pilot Early Discharge Program

Introduction: Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT), with over 12,000 transplants per year in Europe. Due to low toxicity, an entirely outpatient procedure or an early discharge after ASCT can be considered as alternatives to inpatient transplantation. Thus, we launched an Early Discharge Program (EDP) for patients qualified for ASCT due to MM who were under 60 years of age, without significant comorbidities, who had a caregiver available 24/7, and who lived within a 60-minute drive of our hospital. Material and methods: Patients spent 72 hours in the hospital being administered melphalan 200 mg/m2 intravenous followed by an infusion of hematopoietic stem cells. They were eventually discharged and remained under outpatient care. The program was launched in September 2019 and was temporarily halted due to the coronavirus disease 19 (COVID-19) pandemic in early 2020. Five patients were enrolled to the EDP. Results: Non-hematological toxicity was mild and manageable in an outpatient setting. Only one patient was readmitted due to exacerbation of ulcerative colitis that was probably not related to ASCT. We observed neither infections nor bleeding. Due to hematological toxicity, three of the five patients received platelet transfusion on the 6th day after ASCT as outpatients. No packed erythrocytes were transfused. The EDP demonstrated lower costs compared to an inpatient approach. Conclusions: We believe that early discharge, which is an intermediate step to full at-home transplantation due to patients’ wellbeing, reduction of infections caused by resistant microorganisms, and costs, will eventually replace a full inpatient procedure for a significant population of patients suffering from multiple myeloma and indeed other diseases

CAR-T cell therapy – toxicity and its management

Chimeric antigen receptor T-cell (CAR-T) therapy is an effective new treatment for hematologic malignancies. Two anti-CD19 CAR-T products, namely axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additionally, tisagenlecleucel is indicated for refractory acute lymphoblastic leukemia in pediatric patients and young adults up to 25 years of age. CAR-T cells are undoubtedly a major breakthrough therapy in hematooncology resulting in up to 90% response rate with durable remissions in population with refractory high-risk disease. However, there are serious side effects resulting from CAR-T therapy, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Manifestations of CRS mostly include fever, hypotension, hypoxia, and end organ dysfunction. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasia, seizures, and cerebral edema. Since the symptoms are potentially severe, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. In this article, we present a practical guideline for diagnosis, grading and management of CRS and CAR-T neurotoxicity. In addition, infectious complications and late toxicities including prolonged cytopenias and hypogammaglobulinemia are discussed

Neutropenic enterocolitis and multidrug-resistant bacteria colonization in lymphoma patients undergoing autologous stem cell transplantation

Introduction: There is little iterature data regarding neutropenic enterocolitis (NE) development after autologous hematopoietic cell transplantation (auto-HCT) in non-Hodgkin lymphoma (NHL) patients. The aim of this study was to determine the incidence, risk factors, and clinical outcome of NE after auto-HCT in NHL patients with respect to the impact of multidrug-resistant Gram-negative bacteria (MDRG) and vancomycin-resistant enterococci colonization on the early outcome after auto-HCT. Material and methods: This retrospective single-center analysis included a total of 65 NHL patients who underwent auto-HCT after BEAM (BCNU, etoposide, cytosine arabinoside, melphalan) conditioning (BEAM-auto-HCT). Results: NE was diagnosed in nine (13.8%) patients, a median four days after auto-HCT. In 6/9 (66%) patients, septic shock following NE was diagnosed. In univariate analysis, MDRG colonization before BEAM-auto-HCT was the only factor significant for NE development [odds ratio (OR) 2.4 (1.14–5.0), p = 0.027], although this was not confirmed in multivariate analysis. Additionally, NE [OR 5.2 (1.9–13.9), p = 0.001] and MDRG colonization prior to transplant [OR 2.7 (1.0–7.0), p = 0.041] were independent factors for septic shock development. Conclusions: Our findings suggest that NHL patients presenting with MDRG colonization before transplant should be kept under careful surveillance because of the high risk of the development of early severe infectious complications, including abdominal ones

Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission : long-term outcome and risk factors analysis

This report is a retrospective analysis of 65 patients with peripheral T cell lymphoma (PTCL), who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) as a consolidation of first response achieved with either induction or salvage chemotherapy. We intended to determine the prognostic factors that influenced outcome after autoHCT and to define the predictive value of the scoring systems most often applied for transplant outcomes. Nineteen patients in either complete or partial remission underwent autoHCT after induction chemotherapy. Forty-six patients received second-line chemotherapy as a consolidation of partial response after induction chemotherapy (n = 34) or as a salvage therapy after primary induction failure (n = 12), and thereafter proceeded to autoHCT. Finally, the 36 patients were in complete remission, and 29 in partial remission at autoHCT. The median follow-up of survivors was 53 months (range 7–157 months). The 5-year overall survival and progression-free survival for all patients were 61.5 % (95 % CI 47.0–74.2 %) and 59.4 % (95 % CI 46.1–71.5 %), respectively. In multivariate analysis, bone marrow involvement at diagnosis and less than partial remission after induction chemotherapy were factors independently predictive for overall survival and progression-free survival. The prognostic index for PTCL could reliably stratify the prognosis of PTCL in this analysis

Nivolumab for relapsed/refractory classical Hodgkin lymphoma after brentuximab vedotin failure – Polish Lymphoma Research Group real-life experience

AimPolish centers analyzed retrospectively the real-life experience with nivolumab in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) patients, after brentuximab vedotin (BV ) failure. BackgroundDespite the effective frontline treatment, for cHL patients relapsing after autologous stem cell transplantation, the only effective strategy remains the novel agents. Nivolumab, a checkpoint inhibitor, demonstrates the clinical benefit with an acceptable safety profile. Materials and methodsRetrospective analysis included 16 adult patients with R/R cHL after BV failure. All patients received single-agent nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. ResultsAfter six cycles of nivolumab the overall response rate was 81% (complete remission rate of 56%, partial remission rate of 25%). The median PFS was not reached after a median follow-up of 19 months. Adverse events (AEs) of any grade occurred in 12 patients (75%), including grade 3 AEs observed in 5 patients (31%). There were no AEs of grade 4 or 5. After a median of 25 nivolumab doses, 62% of responding patients proceeded to allogeneic stem cell transplantation. ConclusionNivolumab monotherapy demonstrated a high efficacy and safety in R/R cHL patients after BV failure. More patients and longer follow-up may further establish the potential benefit

Road to clinical implementation of CAR-T technology in Poznań

The objective of this paper is to present the process of the national and international accreditation leading to the establishment of the first certified chimeric antigen receptor T (CAR-T) Cell Unit in Poland on the basis of the Department of Hematology and Bone Marrow Transplantation in Poznan University of Medical Sciences and first successful CAR-T therapy in Poland. During 12 months from the initial decision to establish the CAR-T Cell Unit to the application of CAR-T cell treatment in the first patient, the center had to undergo the multidisciplinary external and internal training, as well as the adaptation of multiple procedures within the Transplant Unit and Stem Cell Bank. In order to get accreditation for the implementation of CAR-T cell therapy, an initial training of the team involved in handling cellular products and patient care was organized and updated as a continuous process. The Department fulfilled the site-selection international criteria. The first patient diagnosed for refractory/relapsed DLBCL was qualified, and finally CAR-T cells were administered with successful clinical outcome

The Application of Visible and Near-Infrared Spectroscopy Combined with Chemometrics in Classification of Dried Herbs

The fast differentiation and classification of herb samples are complicated processes due to the presence of many various chemical compounds. Traditionally, separation techniques have been employed for the identification and quantification of compounds present in different plant matrices, but they are tedious, time-consuming and destructive. Thus, a non-targeted approach would be specifically advantageous for this purpose. In the present study, spectroscopy in the visible and near-infrared range and pattern recognition techniques, including the principal component analysis (PCA), linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), regularized discriminant analysis (RDA), super k-nearest neighbor (SKNN) and support vector machine (SVM) techniques, were applied to develop classification models that enabled the discrimination of various commercial dried herbs, including mint, linden, nettle, sage and chamomile. The classification error rates in the validation data were below 10% for all the classification methods, except for SKNN. The results obtained confirm that spectroscopy and pattern recognition methods constitute a good non-destructive tool for the rapid identification of herb species that can be used in routine quality control by the pharmaceutical industry, as well as herbal suppliers, to avoid mislabeling