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Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or –1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).

Hematopoietic stem cell transplantation (HSCT) represents an example of a highly complex and costly medical procedure with major applications in hematology and oncology. It is associated with life-threatening complications and, consequently, increased demands on healthcare resources. Although improving quality is an integral component of healthcare strategic planning, drivers of quality may be variable, and there is logical debate as to what drives quality in HSCT. Moreover, HSCT programs differ in structure and availability of resources, which drive the type of transplantations provided and determine what is affordable and/or economically feasible. The complexity of HSCT procedures with involvement of different stakeholders necessitates not only regulatory frameworks, but also robust quality systems to ensure consistent standards, demonstrate transparency for regulators, and define what quality means within the HSCT program. In an era of escalating healthcare complexity and heightened fiscal responsibility, transparency and accountability, accreditation contributes to ensuring that care meets the highest standards and can serve as a risk mitigation strategy. Quality management has become an indispensable tool for the management of a complex medical intervention such as HSCT. It allows the transplantation team to monitor its activities and identify areas for continuous improvement. The Worldwide Network for Blood and Marrow Transplantation invited a group of international experts in HSCT and quality management to work on providing a summary document about the key elements in quality and accreditation in HSCT and highlight the foremost challenges of implementing them, with a special focus on low- and middle-income economies.

The contribution of related donors to the globally rising number of allogeneic haematopoietic stem cell transplantations (HSCT) remains increasingly important, particularly because of the growing use of haploidentical HSCT. Compared with the strict recommendations on the suitability for unrelated donors, criteria for related donors allow for more discretion and vary between centres. In 2015, the donor outcome committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) proposed consensus recommendations of suitability criteria for paediatric and adult related donors. This Review provides updates and additions to these recommendations from a panel of experts with global representation, including the WBMT, the European Society for Blood and Marrow Transplantation donor outcome committee, the Center for International Blood and Marrow Transplant Research donor health and safety committee, the US National Marrow Donor Program, and the World Marrow Donor Association, after review of the current literature and guidelines. Sections on the suitability of related donors who would not qualify as unrelated donors have been updated. Sections on communicable diseases, clonal haematopoiesis of indeterminate potential, paediatric aspects including psychological issues, and reporting on serious adverse events have been added. The intention of this Review is to support decision making, with the goal of minimising the medical risk to the donor and protecting the recipient from transmissible diseases.

Haematopoietic progenitor cell donation from bone marrow and mobilised peripheral blood obtained from related and unrelated donors is an established procedure. The donation process in general has proven to be safe, but in rare cases severe and even fatal events have been reported. The present study aimed at providing a description of the current situation of donor protection measures in Council of Europe member states. A specific questionnaire was developed to compile information on donation activities, graft sources, legal frameworks, donor protection measures, collection of donor outcome data, and long-term follow-up of paediatric and adult related and unrelated donors. The outcome of this survey served as a basis for elaborating the Recommendation CM/Rec(2020)6 of the Committee of Ministers to member States on establishing harmonised measures for the protection of haematopoietic progenitor cell donors.

Summary Background In the primary analysis of the pivotal JULIET trial of tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, the best overall response rate was 52% and the complete response rate was 40% in 93 evaluable adult patients with relapsed or refractory aggressive B-cell lymphomas. We aimed to do a long-term follow-up analysis of the clinical outcomes and correlative analyses of activity and safety in the full adult cohort. Methods In this multicentre, open-label, single-arm, phase 2 trial (JULIET) done at 27 treatment sites in ten countries (Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, and the USA), adult patients (≥18 years) with histologically confirmed relapsed or refractory large B-cell lymphomas who were ineligible for, did not consent to, or had disease progression after autologous haematopoietic stem-cell transplantation, with an Eastern Cooperative Oncology Group performance status of 0–1 at screening, were enrolled. Patients received a single intravenous infusion of tisagenlecleucel (target dose 5 × 108 viable transduced CAR T cells). The primary endpoint was overall response rate (ie, the proportion of patients with a best overall disease response of a complete response or partial response using the Lugano classification, as assessed by an independent review committee) at any time post-infusion and was analysed in all patients who received tisagenlecleucel (the full analysis set). Safety was analysed in all patients who received tisagenlecleucel. JULIET is registered with ClinialTrials.gov , NCT02445248 , and is ongoing. Findings Between July 29, 2015, and Nov 2, 2017, 167 patients were enrolled. As of Feb 20, 2020, 115 patients had received tisagenlecleucel infusion and were included in the full analysis set. At a median follow-up of 40·3 months (IQR 37·8–43·8), the overall response rate was 53·0% (95% CI 43·5–62·4; 61 of 115 patients), with 45 (39%) patients having a complete response as their best overall response. The most common grade 3–4 adverse events were anaemia (45 [39%]), decreased neutrophil count (39 [34%]), decreased white blood cell count (37 [32%]), decreased platelet count (32 [28%]), cytokine release syndrome (26 [23%]), neutropenia (23 [20%]), febrile neutropenia (19 [17%]), hypophosphataemia (15 [13%]), and thrombocytopenia (14 [12%]). The most common treatment-related serious adverse events were cytokine release syndrome (31 [27%]), febrile neutropenia (seven [6%]), pyrexia (six [5%]), pancytopenia (three [3%]), and pneumonia (three [3%]). No treatment-related deaths were reported. Interpretation Tisagenlecleucel shows durable activity and manageable safety profiles in adult patients with relapsed or refractory aggressive B-cell lymphomas. For patients with large B-cell lymphomas that are refractory to chemoimmunotherapy or relapsing after second-line therapies, tisagenlecleucel compares favourably with respect to risk–benefit relative to conventional therapeutic approaches (eg, salvage chemotherapy). Funding Novartis Pharmaceuticals.

Autologous stem cell transplantation is routinely used in the management of several hematological diseases, solid tumors, and immune disorders. Peripheral blood stem cell (PBSC) collection performed by apheresis is the preferred source of stem cells. In this study, the potential impact of mobilization regimens on the performance of the Spectra Optia® continuous mononuclear cell collection system was evaluated. We performed a retrospective data analysis for patients undergoing autologous PBSC collection at the Medical University Vienna, Vienna General Hospital between September 2016 and June 2018. Collections were divided into two main groups according to the mobilization regimen received: without (210 collections) or with (99 collections) plerixafor. Assessed variables included product characteristics and collection efficiency (CE). Overall, product characteristics were similar between the groups. Median CD34+ CE2 was 50.1% versus 53.0%, and CE1 was 66.9% versus 69.9% following mobilization without and with plerixafor, respectively; the difference was not statistically significant. Simple linear regression showed a very weak positive correlation between the mobilization method and CE1 or CE2 (mobilization with plerixafor increased CE2 by 4.106%). In conclusion, the Spectra Optia® apheresis system led to high CE and a good quality of PBSC products when mobilization regimens with or without plerixafor were used.

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and CAR-T cell exhaustion were observed in patients with PD-1 overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR-T cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received one tisagenlecleucel infusion on Day 1. Pembrolizumab 200 mg was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on Days 15 (n=4), 8 (n=4), or -1 (n=4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel and pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).

Immune checkpoint control is one of several mechanisms that negatively influence the immune system and contribute to the development and progression of cancer. To enhance anti-tumor immune responses in patients with advanced solid tumors, we employ a novel autologous cancer cell therapy, APN401, which allows transient and highly specific silencing of Casitas B-lineage lymphoma-b (Cbl-b) in patients’ peripheral mononuclear cells (PBMCs). Cbl-b is an E3 ubiquitin protein ligase that plays a central role in both innate and adaptive immune responses. Here we present two patients with advanced, metastatic solid tumors: one patient diagnosed with appendix carcinoma, and one patient diagnosed with head and neck squamous cell carcinoma (HNSCC). Both showed stable disease (SD) during treatment with APN401. In an open-label, multicenter Phase Ib trial, two increasing dose levels of APN401 were evaluated in patients with advanced solid tumors. Using invIOs’s closed cell-processing platform - Enhancement Platform for immune Cells (EPiC) - patients’ PBMCs were purified from leukapheresis products and subsequently transfected with a small interfering ribonucleic acid (siRNA) to specifically block Cbl-b expression. The entire manufacturing process required less than six hours, and the drug product could be reinfused on the same day. The trial evaluated safety and clinical outcomes, as well as the activity and potency of the drug product. Additionally, various biomarkers were analyzed in patients’ peripheral blood, which was collected prior to each treatment cycle. Two patients, one with appendix carcinoma and one with HNSCC, showed stable disease after repeated APN401 treatments at the lowest and/or intermediate dose levels. Subsequent drug product analyses revealed increased IL-2 levels and elevated CD8/CD4 ratios, suggesting potential cytotoxic efficacy. In stimulation assays with HLA class I-restricted viral or tumor antigens, increased IFN-γ levels were detected and served as surrogate markers for improved immunity and tumor reactivity. 10X genomics and TCR clonotyping revealed clonal expansion of T cell subsets throughout the course of the treatment. Taken together, these initial results indicate that APN401, a novel personalized cancer cell therapy based on targeted silencing of Cbl-b in PBMCs, may be a safe and effective immunotherapy for solid tumors. This cell therapy will be further evaluated as a monotherapy along with potential combinations in clinical trials in various solid tumors. Ethics approval: The clinical trial was approved by the Medical University of Vienna institution’s independent Ethics Committee, approval number 1778/2020. Citation Format: Mario Kuttke, Alexander Dohnal, Andreas Tanzmann, Beate Pribitzer, Felix Batrina, Stefan Bunka, Sophia Spagl, Manuela Branka, Sarah Bischof, Kathrin Thell, Maria Urban, Hannes Muehleisen, Bernhard Peball, Bianca Gapp, Angela Halfmann, Markus Raderer, Gerald Prager, Thorsten Fuereder, Romana Gugenberger, Nina Worel. Case report: APN401, a novel cancer therapy using Cbl-b silenced autologous PBMCs, induced stable disease in two patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB187.

SummaryChimeric antigen receptor T cells (CAR-T cells) are a novel form of cellular immunotherapy for patients with hematologic and oncologic malignancies. Known side effects of these approved cellular immunotherapies are cytokine release syndrome, immune-cell associated neurotoxicity syndrome, cytopenias, infections and long-lasting B cell aplasia. Safe administration of CAR-T cell therapy requires thorough patient selection and patient care in qualified CAR-T cell centers.

SummaryDiffuse large B‑cell lymphoma (DLBCL) comprises 30–40% of non-Hodgkin’s lymphoma. Clinical factors such as a high International Prognostic Index (IPI) or molecular factors as cell of origin (COO) have an influence on the clinical outcome after conventional immunochemotherapy. Patients with resistant or relapsed (r/r) DLBCL have a poor prognosis with a median overall survival of 6,3 months and low complete response rates (CR 7%) to salvage chemoimmunotherapy. Currently, therapy with autologous chimeric antigen receptor T‑cells (CAR T‑cells) provide encouraging complete responses (CR) of up to 50%. However, high costs for approved products and elaborate logistics have to be encountered.

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8–10 ng/ml, months 1–6; 5–8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p &lt, 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.

We analysed iron biomarkers and their relationships in 30 subjects with HFE mutations and moderate hyperferritinaemia undergoing iron removal at our blood donation centre. Body mass index (BMI) and liver enzymes were assessed. Serum iron (SI), ferritin, transferrin saturation (TSAT), hepcidin and non-transferrin bound iron (NTBI) were measured serially. Seventeen subjects had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median age (p = 0.582), BMI (p = 0.500) and ferritin (p = 0.089) were comparable. At baseline, 12/17 p.C282Y/p.C282Y and 2/9 p.C282Y/p.H63D had measurable NTBI (p = 0.003). The p.C282Y/p.C282Y had higher TSAT (p 0.001), lower hepcidin (p = 0.031) and hepcidin/ferritin ratio (p = 0.073). After treatment, iron indices were similar among groups, except TSAT (higher in p.C282Y/p.C282Y; p = 0.06). Strong relationships were observed between ferritin and TSAT (R = 0.71), NTBI and TSAT (R = 0.61), NTBI and SI (R = 0.54) in p.C282Y/p.C282Y. Hepcidin correlated weakly with ferritin in p.C282Y/p.C282Y (R = 0.37) but strongly in p.C282Y/p.H63D (R = 0.66) and p.H63D/p.H63D (R = 0.72), while relationships with TSAT were weak (R = 0.27), moderate (R = 0.55) and strong (R = 0.61), respectively. Low penetrance p.C282Y/p.C282Y phenotype displays hepcidin dysregulation and biochemical risk for iron toxicity.

ZusammenfassungÜber viele Dekaden hinweg war für die Behandlung hämatologischer Erkrankungen die einzige akzeptierte zelluläre Therapie die Transplantation von hämatopoetischen Stamm- und Progenitorzellpräparationen, autolog oder allogen, nach vorheriger Konditionierung als individualisierte Therapieform etabliert. Dabei impliziert diese Art der Therapie aus rechtlicher Sicht nur minimale Manipulationen der Transplantate (Zentrifugation, Konzentrierung, Verdünnung, immunmagnetische Anreicherung oder Depletionen, Kryokonservierung), sodass die Gewinnung, Verarbeitung, Qualitätskontrolle und Abgabe der Stammzell-/Immuntherapeutika zumeist komplett in der Hand transfusionsmedizinischer Institutionen liegen. Nach der Zulassung durch die Europäische Arzneimittelbehörde (EMA) im August 2018 sind erstmals kommerziell erhältliche, autologe chimäre Antigen-Rezeptor-T-Zellen (chimeric antigen-receptor-T-cells, CAR-T-cells) in Deutschland sowie einer Vielzahl anderer europäischer Länder für die individualisierte Therapie von Patienten mit ausgewählten malignen Neoplasien der B-Zell-Reihe verfügbar. Im Rahmen einer gemeinsamen Sitzung der Sektion „Stammzelltransplantation und Zelltherapie“ und der Sektion „Präparative und therapeutische Apherese“ der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI) am 19.10.2018 in Frankfurt wurden mehrere Impulsvorträge zum Thema „Zugelassene CAR-T-Zell-Therapie ante portas: Rolle der Transfusionsmedizin“ gehalten. Dabei wurden die Themen Finanzierung und Kostenerstattung, regulatorische und rechtliche Rahmenbedingungen sowie verschiedene Aspekte der notwendigen Verantwortungsabgrenzung zwischen dem Hersteller des Ausgangsmaterials, dem pharmazeutischen Unternehmen und dem klinischen Anwender ausführlich diskutiert.

The section “Preparative and Therapeutic Hemapheresis” of the German Society for Transfusion Medicine and Immunohematology (DGTI) has reviewed the actual literature and updated techniques and indications for evidence-based use of therapeutic apheresis in human disease. The recommendations are mostly in line with the “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice” published by the Writing Committee of the American Society for Apheresis (ASFA) and have been conducted by experts from the DACH (Germany, Austria, Switzerland) region.

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCT were performed by 2019 since 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCT were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCT are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated HCT is plateauing and cord blood HCT is in decline.

Highlights • The COVID-19 pandemic has a major impact on the field of hematopoietic stem cell transplantation. • SARS-CoV-2 testing strategy in stem cell donors has been implemented but was not available in every center from the early beginning of the pandemic. • Changes in daily routine (e.g. freezing of unrelated stem cell products) became necessary. • Limited available data in COVID-19 infected donors and patients show no increase in severe events and adverse reactions due to concomitant G-CSF administration and no virus transmission of positive tested donors., SARS-CoV-2 has spread rapidly worldwide, but the full impact of the COVID-19 pandemic on the field of hematopoietic cell transplantation (HCT) remains unknown. To understand this better, an 18-item online survey was disseminated by the Worldwide Network for Blood & Marrow Transplantation with questions exploring SARS-CoV-2 testing algorithms, mobilization, and cryopreservation strategies and COVID-19 infections in allogeneic related and autologous hematopoietic progenitor cell (HPC) donors. The aim of this survey was to assess the impact of the outbreak on policies relating to HPC mobilization, collection, and processing with respect to changes in daily routine. A total of 91 individual responses from distinct centers in 6 continents were available for analysis. In these centers, the majority (72%) of allogeneic related and autologous donors are routinely tested for SARS-CoV-2 before HPC collection, and 80% of centers implement cryopreservation of allogeneic HPC grafts before commencing conditioning regimens in patients. Five related and 14 autologous donors who tested positive for COVID-19 did not experience any unexpected adverse events or reactions during growth factor administration (eg, hyperinflammatory syndrome). These data are limited by the small number of survey respondents but nonetheless suggest that centers are following the recommendations of appropriate scientific organizations and provide some preliminary data to suggest areas of further study.

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Background Extracorporeal photopheresis (ECP) has demonstrated efficacy as second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD). The aim of our study was to analyze whether the amount of ECP-treated cells in patients with SR, aGVHD has an impact on response at 1 month. Study design and methods Data on white blood cells, lymphocytes, monocytes, mononuclear cells, and neutrophils, including absolute counts and counts per kilogram of body weight in ECP products from patients with aGVHD, were collected. For each cell population, the median dose per single ECP and the cumulative doses collected during the first week and the first month of treatment were compared with the response to ECP. Results In total, 99 patients underwent 1215 ECP procedures. Overall response was defined as a complete response if all signs of aGVHD resolved or a partial response if greater than 50% resolution was reached without other, additional immunosuppression. An overall response was obtained by 75% of patients, including 53% complete responses. Univariate analysis showed a correlation of lymphocytes and mononuclear cells/kg body weight for a single procedure and overall response. In logistic regression analysis, no tested variable had an influence on response. In receiver operating characteristic curve analysis, cutoffs of 8.4 × 106 /kg body weight lymphocytes and 13.9 × 106 /kg body weight mononuclear cells were associated with an overall response to ECP at 1 month with 75% sensitivity. Conclusion Our results in patients with steroid-refractory aGVHD confirm that response rates to ECP are high and that certain cutoff values for lymphocytes and mononuclear cells/kg body weight in each individual procedure can predict an overall response to ECP at 1 month.

Hematopoietic stem cell transplantation (HSCT) is an established treatment for patients with severe congenital or acquired hemato-/oncological disorders. Despite major improvements, HSCT remains associated with substantial morbidity and mortality. Implementation of a quality management system has become standard practice not only for industries when their products or services are associated with significant risks to human safety but also in the healthcare sector. The use of a quality management system contributes to better products and services and improved patient’s outcome after medical interventions. Members of the Alliance for Harmonization of Cellular Therapy Accreditation prepared the document Essential Elements, which is intended to serve as a guide for establishing a quality program for new or developing HSCT programs. It is intended for use as a resource and does not contain the full requirements of all standards but seeks to provide clear examples of compliance to support basic quality system elements. The content is based on common elements found in already existing standards with a major focus on the establishment of a quality program that applies to the entire transplant program. Essential Elements is structured as an explanation helping to understand the intent of the element giving guidance what is needed, and examples showing how the element applies. Centers seeking accreditation are subjected to a detailed document review, on-site inspection and follow-up procedure. In conclusion, new and developing stem cell transplantation programs should focus on quality and safety and step on the path towards full accreditation. The HSCT community must continue its efforts to offer education and training to support developing programs to attain accreditation. Keywords: Stem cell transplantation, Quality management sytem, Accreditation

BACKGROUND Peripheral blood stem cells mobilized with granulocyte–colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens. STUDY DESIGN AND METHODS We used a recently established single-platform multicolor flow-cytometric analysis including CD45RA and CD133 to define CD34+ subpopulations and lymphocyte subsets in products obtained either after G-CSF with or without chemotherapy alone (G, n = 40) or with addition of plerixafor (GP, n = 40). RESULTS Absolute numbers of white blood cells and lymphocyte subtypes were significantly higher after plerixafor, which was not observed for absolute CD34+ counts. However, distinct differences in terms of CD34+ subtypes were observed. The most primitive multipotent progenitors (CD45RA–CD133+CD34+CD38low) predominated significantly after G (median, 49.2%; range, 15.2%-63%) compared to GP (median, 34.4%; range, 12%-62%; p