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

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

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

The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia

Background and Objectives Numerous studies have confirmed the influence of diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is chiefly metabolised by glucuronidation and sulphation. This study assessed the influence of diabetes on the pharmacokinetics of paracetamol and its metabolites: glucuronide (APAP-glu) and sulfate (APAP-sulfate) in FN patients. Methods Patients with FN received single intravenous dose 1000 mg of APAP. The FN patients were allocated to one of two groups: diabetics (DG, n = 7) or non-diabetics (NDG, n = 11). The plasma concentrations of paracetamol and its metabolites were measured with the validated high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results Pharmacokinetic parameters (mean [SD]) of APAP in the DG and NDG groups were as follows: Cmax (maximum comcentration) = 21.50 [11.23] vs. 23.42 [9.79] mg/L, AUC 0–t (area under the concentration–time curve) = 44.23 [17.93] vs. 41.43 [14.57] mg·h/L, t1/2kel (elimination half-life) = 2.28 [0.80] vs. 2.11 [0.80] h. In both groups the exposure to APAP was comparable. The study did not reveal differences between the two groups in the pharmacokinetics of APAP-glu and APAP-sulfate. The Cmax and AUC 0–t ratio between the metabolites and APAP were similar. Conclusions No differences in the pharmacokinetics of APAP, APAP-glu and APAP-sulfate in patients with FN indicates that diabetes does not influence glucuronidation and sulfatation of paracetamol

Real-life experiences of letermovir prophylaxis for cytomegalovirus infection in patients after hematopoietic stem cell transplantation: Polish Acute Leukemia Group (PALG) analysis

Introduction: Letermovir (LMV) is a new, cytomegalovirus (CMV)-specific, antiviral drug, approved in 2018 for CMV prophylaxis in patients after allogeneic hematopoietic transplantation. The introduction of letermovir prophylaxis has changed the management of CMV infection: it has reduced the incidence of CMV infections and CMV-related complications, and also improved the overall survival in CMV seropositive patients. However, until recently, due to its high treatment cost, prophylaxis with letermovir has not beeen a standard of care in Poland. Material and methods: To confirm the effectiveness and safety of letermovir prophylaxis, we collected real-life data from eight Polish transplant centers, in which a total of 53 patients were treated with letermovir, including off-label use. Results: LMV is characterized by low toxicity and good tolerability. There were no reports of special adverse events caused by LMV. Conclusions: Our experiences confirm the effectiveness and safety of letermovir prophylaxis, and suggest that this prophylaxis should be started as soon as possible after the infusion of stem cells, preferably no later than day 14. Moreover, our findings indicate that some patients could benefit from extended letermovir prophylaxis beyond 100 days after transplant

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