Position statement from the British Society of Blood and Marrow Transplantation and Cellular Therapy on insertional oncogenesis in gene-engineered advanced cell therapy products for treatment of haematological disorders.

Germline predisposition to haematological cancers is increasingly being recognised. Widespread adoption of high-throughput and whole genome sequencing is identifying large numbers of causative germline mutations. Constitutional pathogenic variants in six genes (DEAD-box helicase 41 [DDX41], ETS variant transcription factor 6 [ETV6], CCAAT enhancer binding protein alpha [CEBPA], RUNX family transcription factor 1 [RUNX1], ankyrin repeat domain containing 26 [ANKRD26] and GATA binding protein 2 [GATA2]) are particularly significant in increasing the risk of haematological cancers, with variants in some of these genes also associated with non-malignant syndromic features. Allogeneic blood and marrow transplantation (BMT) is central to management in many haematological cancers. Identification of germline variants may have implications for the patient and potential family donors. Beyond selection of an appropriate haematopoietic stem cell donor there may be sensitive issues surrounding identification and counselling of hitherto asymptomatic relatives. If BMT is needed, there is frequently a clinical urgency that demands a rapid integrated multidisciplinary approach to testing and decision making involving haematologists in collaboration with Clinical and Laboratory Geneticists. Here, we present best practice consensus guidelines arrived at following a meeting convened by the UK Cancer Genetics Group (UKCGG), the Cancer Research UK (CRUK) funded CanGene-CanVar research programme (CGCV), NHS England Genomic Laboratory Hub (GLH) Haematological Oncology Malignancies Working Group and the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT).

Safe and effective haematopoietic stem cell transplant (HSCT) programmes require adequately resourced, well-trained and experienced multidisciplinary teams. Resources need to be at a level which provides flexibility for development, as indications for HSCT expand and new therapeutic approaches move from experimental to standard practice. The Paediatric British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT) group established a working party (WP) to survey the current workforce, to examine the evidence for workforce requirements and to produce recommendations for the medical, nursing, data management, HSCT coordination, quality management, pharmacy and allied health professional workforce requirements for the provision of a safe and effective paediatric transplant centre (TC). These complement the Joint Accreditation Committee of the International Society for Cell and Gene Therapy (ISCT)-Europe & European Society for Blood and Marrow Transplantation (EBMT) (JACIE) guidance. The WP included representation from haematological and immunological backgrounds, and TCs of different sizes and specialty interests with geographical representation within the UK and Republic of Ireland while consultations were held with a breadth of multidisciplinary groups.

The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). All French AD patients (≥ 18years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM). Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83months (38-130), OS at 5 and 10years were 77% (95% CI 68.5-86.2) and 64% (95% CI 51.7-76.3), and for PFS 51% (95% CI 40.4-61.6) and 44% (95% CI 32.8-55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0-15.5) at day 100, 9.8% (95% CI 4.8-16.9) at 5years and 13.6% (95% CI 6.9-22.5) at 10years. This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.

Peripheral Blood Stem Cells Vs Bone Marrow: Stem Cell Source Comparison for Patients Acute Myeloid Leukemia and Myelodysplastic Syndrome Receiving an Allogeneic Stem Cell Transplantation from a 10/10 Matched Donor. Study from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Handling, processing and disposal of stem cell products in Europe: A survey by the cellular therapy and immunobiology working party of the European Society for Blood and Marrow Transplantation

Current challenges in cell and gene therapy: a joint view from the European Committee of the International Society for Cell & Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT)

Recognition of Hematopoietic Stem Cell Transplantation and Cellular Therapy Expertise to Promote Care Accessibility: A Formally Credentialed Area of Focused Competence in Canada

Summary of the Third International Workshop on Clinical Tolerance.

This article analyzes current data, and the main challenges faced in Hematopoietic cell Transplantation (HCT) in Brazil, as presented at the SBTMO 2024 meeting, with the aim of guiding future actions. Topics discussed included the waiting list for HCT transplants, access to beds for adults and pediatric patients, and the need for a more efficient distribution of resources across the country. Among the identified needs were the creation of a program to expand access to transplants through the Brazilian Unified Health System (SUS), the importance of health registries for data-driven decisions, and the development of the "Mais Saúde Amazônia" project to expand transplant centers in the Amazon region. Additionally, the provision of financial incentives for transplant centers, the implementation of mentorship programs to increase access to HCT, and the formation of a cooperative network between SBTMO (Brazilian Society of Bone Marrow Transplantation and Cellular Therapy), ABHH (Brazilian Association of Hematology, Hemotherapy, and Cellular Therapy), ANVISA (Brazilian Health Regulatory Agency), ABRALE (Brazilian Association of Lymphoma and Leukemia), and INCA (Brazilian National Cancer Institute) to improve the integration of HCT services were discussed

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.

Effect of Cryopreservation in Unrelated Bone Marrow and Peripheral Blood Stem Cell Transplantation in the Era of the COVID-19 Pandemic: An Update from the Japan Marrow Donor Program

Autologous Hematopoietic Stem Cell Transplantation (AHSCT) in Severe Auto-Immune Disease Adult Patients: Analysis of Outcomes from the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGMT-TC) in Light of the European Society for Blood and Marrow Transplantation (EBMT) Activity

Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research

SummaryIn allogeneic haematopoietic stem cell transplantation (HSCT), important clinical decisions depend upon assessment of chimerism, including immunosuppressant dosing and donor lymphocyte infusions (DLI), which in turn can have major impacts on disease control, graft‐versus‐host disease (GVHD), immunity and ultimately patient survival. There is a complex range of clinical and laboratory procedural considerations including methodology of testing, types of cell subset selection, frequency of testing, urgency of turnaround times (TATs), interplay with measurable residual disease (MRD) monitoring and duration of testing post‐transplant. These aspects are routinely adapted according to disease indication, patient characteristics, donor source and intensity of transplant technique. To encourage the harmonisation of clinical and laboratory practice in the United Kingdom, we held a national workshop meeting to bring together key stakeholders to review the current literature with a view to producing a state‐of‐the‐art position paper. Here, we present best practice consensus recommendations and identify key areas for future audit and research from the UK Cancer Genetics Group (UKCGG), NHS England Genomic Laboratory Hub (GLH) Haematological Oncology Malignancies Working Group, UK National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) and the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT).

Autoimmune diseases (ADs) represent a heterogenous group of complex diseases with increasing incidence in Western countries and are a major cause of morbidity. Hematopoietic stem cell transplantation (HSCT) has evolved over the last 25 years as a specific treatment for patients with severe ADs, through eradication of the pathogenic immunologic memory and profound immune renewal. HSCT for ADs is recently facing a unique developmental phase across transplant centers. This review provides a comprehensive overview of the recent evidence and developments in the area, including fundamentals of preclinical research, clinical studies in neurologic, rheumatologic and gastroenterologic diseases, which represent major indications at present, along with evidence of HSCT for rarer indications. Moreover, we describe the interwoven challenges of delivering more advanced cellular therapies, exploiting mesenchymal stem cells, regulatory T cells and potentially CAR-T cell therapies, in patients affected by ADs. Overall, we discuss past and current indications, efficacy, associated risks and benefits, and future directions of HSCT and advanced cellular therapies in the treatment of severe/refractory ADs, integrating the available literature with European Society for Blood and Marrow Transplantation (EBMT) registry data.