BACKGROUND:Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used as a one-off disease-modifying therapy for aggressive forms of multiple sclerosis (MS). We report real-world effectiveness of AHSCT for MS in the UK. METHODS:This retrospective open-label study included patients with (pw)MS treated with AHSCT between 2002 and 2023 in 14 UK centres. Outcomes included relapse-free survival (RFS), MRI activity-free survival (MFS), progression-free survival (PFS) and no evidence of disease activity (NEDA-3). We assessed 6-month confirmed Expanded Disability Status Scale (EDSS) score progression or improvement compared with pre-treatment. Treatment-related mortality (TRM) was defined as death from any cause within 100 days post-autologous graft reinfusion. RESULTS:364 pwMS were included (median age 40 years; 58% female). Of these, 271 pwMS had adequate neurological follow-up data: 168 (62%) had relapsing-remitting MS (pwRRMS) and 103 (38%) had progressive MS (pwPMS). Median disease duration from symptom onset was 10 years (IQR 6-14), EDSS 6 (IQR 4.0-6.5) and follow-up from AHSCT 46 months. At 2 and 5 years from AHSCT, RFS was 94.6% and 88.6%; MFS 93.1% and 80.1%; PFS 83.5% and 62.4%; NEDA-3 72.3% and 46.2%. pwRRMS had significantly higher rates of PFS (p=0.007) and NEDA-3 (p=0.001) than pwPMS. RRMS was a predictor of EDSS improvement, whose prevalence was 24.2% at 2 years and 20.4% at 5 years. TRM was 1.4% (n=5/364). CONCLUSIONS:In this cohort with high EDSS at baseline and including pwPMS, AHSCT led to durable remission of inflammatory activity and stabilisation or improvement of neurological disability, particularly in pwRRMS.

Hematopoietic cell transplantation (HCT) is the gold standard curative therapy for many hematological malignancies, but disease relapse is common and the primary cause of treatment failure. While the impact of matching the classical HLA loci on HCT outcomes is known, the role of the nonclassical HLA class I gene HLA-E is unclear but has been limited to HLA-E*01:01/01:03 thus far. To genotype the full length of HLA-E for a cohort of UK HCT patients and unrelated donors, to enable investigation of all HLA-E alleles. To use this full-length genotyping to investigate any statistical associations of HLA-E matching or genotype with UK HCT patient clinical outcomes. To investigate this, we retrospectively genotyped 1878 UK patients with hematological malignancies and their matched unrelated donors for HLA-E at a definitive allele resolution and analyzed patient outcomes with respect to the HLA-E genetic data using adjusted multivariate analysis models. Multivariate analysis showed that the presence of the allele HLA-E*01:06 in the donor genotype was associated with significantly reduced 5-yr risk of relapse (hazard ratio [HR] = 0.39; P = .002) and increased progression-free and overall survival (HR = 0.59; P = .003 and HR = 0.69; P = .04). We also observed a detrimental impact of the allele HLA-E*01:03:05 in the donor genotype on relapse risk (HR = 2.54; P = .001) and progression-free survival (HR = 1.90; P = .006), compared with donors without this allele. Our data show a potential role for HLA-E in unrelated donor HCT, where donor HLA-E genotypes appear to correlate with patient relapse rates and patient survival. This is the first study to investigate the impact of HLA-E on HCT outcomes using a full-length genotyping strategy, which allowed us to identify potential correlations from alleles beyond HLA-E*01:01/01:03 for the first time.

Background:The participation of transplant centres in research studies that request detailed follow-up data on included patients can be challenging due to the amount of time centre Data Managers have to complete additional requests. The Research Data Manager (RDM) Pilot Project was designed to support Anthony Nolan's longitudinal Patient/Donor project and provide real-world evidence of the benefit of additional and dedicated data management resources in transplant centres. Objectives:For Anthony Nolan to continue advancing the field of donor selection, up-to-date and accurate follow-up data is needed. This 12-month pilot project aimed to demonstrate how on-the-ground support could improve access to outcome data. Study Design:Following RDM placements at two participating centres, we reviewed the data quality and quantity collected, thus ensuring the methods used remain effective and are likely to result in successful and continuous data improvement. The cohort covered a broad timespan and included historical patient records, posing challenges in availability of prior data and long-term follow-up of discharged patients. Results:Following the placements, over 400 patients now have the most up-to-date and complete patient clinical outcome data available within the EBMT/BSBMTCT registry database for any group to study, reducing the burden on these centres to complete research data requests for these individuals. Trial Registration:The authors have confirmed clinical trial registration is not needed for this submission.

Teenage and young adult (TYA) patients undergoing allogeneic stem cell transplant have distinct psychosocial needs, yet they are poorly represented in research and their outcomes are not well understood. This study uses prospectively collected data from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT) registry to explore UK transplant practice and outcomes for TYA patients (aged 16-24) in this healthcare setting, alongside children (aged 1-15) and adults (aged 25-39), transplanted for acute leukaemia (including lymphoblastic, acute lymphoblastic leukaemia [ALL], and myeloid, acute myeloid leukaemia [AML]). Nine hundred and forty TYA patients, transplanted between 1999 and 2018, are included, representing 87% of all UK activity during the study period. On adjusted analyses, overall survival after transplant for ALL worsened from children, through TYA, to adults; survival for patients with AML was similar across age groups. Non-relapse mortality was not significantly worse in TYA patients compared with children (p = 0.117 in ALL, p = 0.379 in AML). The risk of chronic graft-versus-host disease (GvHD) was strongly correlated with age, with rates in the TYA group much closer to those seen in adults. While a graft-versus-leukaemia effect may be suppressing relapse, the high rate of GvHD represents an unmet need in this group, who are at a crucial juncture in their personal, educational and social development.

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.

Autologous haematopoietic stem cell transplantation (AHSCT) has been developed as a treatment for multiple sclerosis (MS) since 1995. The United Kingdom is one of the most active countries performing AHSCT for MS in Europe. We report the UK experience of AHSCT for MS in 364 patients with MS treated with AHSCT between 2002 and 2023. We report transplant-related mortality (TRM), AHSCT complications and efficacy as defined by expanded disability status scale (EDSS) progression-free survival (PFS) at 2 years and 5 years. 209 (58%) had relapsing-remitting MS (RRMS) and 130 (36%) had progressive MS. Median EDSS at the time of HSCT was 6.0 (range: 0-9) and duration of disease was 10 years (range: 4-34). TRM was 1.4%, exclusively occurred in patients with advanced baseline disability (median EDSS: 6.5). Epstein-Barr virus (EBV) reactivation occurred in 75.9% of patients where EBV results were reported (235/311). Overall PFS was 83.5% at 2 years post-HSCT and 62.4% at 5 years. This large study demonstrates the evolution of this one-off treatment across the United Kingdom, its safety and sustained efficacy in patients with severe/refractory MS. The uneven geographical access is a future consideration in equitable delivery across the UK NHS as the evidence base for AHSCT in MS treatment pathways becomes stronger.

The effects of graft cryopreservation on patient outcomes in allogeneic hematopoietic cell transplantation (HCT) remains unclear. In our multicenter UK study, outcomes of 926 adults receiving an allogeneic cryopreserved peripheral blood stem cell (PBSC) graft for a malignant hematologic indication between June 2020 and September 2021 were compared with 1491 adults with hematologic malignancy transplanted June 2018 to September 2019 with fresh PBSC grafts. There were short delays in median platelet and neutrophil engraftment with cryopreserved hematopoietic stem cell (HSC) grafts: 18 versus 15 days (P < .01) for platelets and 14 versus 13 days (P < .01) for neutrophils in the cryopreserved and fresh historical control groups, respectively. Reassuringly, primary graft failure rates were similar (P = .48). Relapse rates were higher (P = .03) but non-relapse mortality was lower (P < .01) in the cryopreserved group at 12-month follow-up. There was no statistical difference in overall survival between the groups (P = .52). Cryopreservation of allogeneic HSC grafts remains an important quality consideration in HCT practice. Advancement of our clinical and scientific understanding of this aspect of laboratory processing of HCT grafts is essential in relation not only to the pandemic but also for its use in other clinical and logistical settings where fresh donations are not feasible.

Background: Allogeneic stem cell transplantation (HCT) is a curative option for patients with acquired severe aplastic anemia (SAA) and inherited BMF syndromes (BMFs). The FCC regimen (fludarabine, cyclophosphamide and alemtuzumab) with cyclosporin (without irradiation and methotrexate) for Graft-versus-Host Disease (GvHD) prophylaxis is UK standard of care due to excellent survival and low GvHD/rejection incidence. FCC is uniformly used across ages, irrespective of BMF etiology. We report 10y outcomes following HCT for SAA and IBMFs reported to the BSBMTCT registry over the last 25 years. Methods: Retrospective data were collected from all SAA and IBMF patients transplanted using HLA 9-10/10 sibling/unrelated donors at 33 UK centres between 1999-2024. Overall survival (OS) and GvHD free, relapse free survival (GFRS) were calculated by Kaplan-Meier method. Comparison between groups was done by Cox regression. Results: 1718 patients (SAA 1374, 80% and IBMF 344, 20%), 888 (52%) pediatric (<18y) and 830 (48%) adult (>18y) patients were studied. SAA comprised 583 children (42%) and 791 adults (58%); median ages 10.5y (IQR 7-14y) and 36y (IQR 24-52y) respectively. 68% had ethnicity data: 83% self-reported white, 17% mixed, Asian or Black. 78% had HCT after 2010, with procedures rising over time ( e.g. 290 in 2019-2024 vs 84 in 2004-2008). Median time from diagnosis to HCT was 4m (IQR 1m-15y, pediatric) and 9m (IQR 1m-34y, adults). 38% of adults and 14% of paediatric SAA cases had HCT >12m after diagnosis. Comorbidity (HCT-CI) was 0-2 in 60% of <18 years and 50% of adults. Conditioning regimen included alemtuzumab in 74% or thymoglobulin in 12%. Alemtuzumab showed increased use in the last decade (87%); 8% incorporated total body irradiation due to HLA mismatch. Cell source was mainly bone marrow (BM) in children (80%) but largely peripheral blood (66%) in adults. 59% of donors were unrelated. IBMF group (Fanconi anemia (50%), Diamond Blackfan Anemia (19%) or telomeropathy (7%)) was mainly pediatric (n=305, 89%). Only 20% of adult cases were IBMFs. Median age at HCT was 7.5y (IQR 5-10y). Alemtuzumab was the commonly used serotherapy (60%) across all age groups; BM was the preferred source in 81% of <18 years compared to 33% of adults. Median follow-up was 5y (IQR 1.3-8.9y). Rates of primary and secondary graft failure were 3% and 2% (children) and 4% and 4% (adults). The rate of grade 2-4 acute GVHD and 1y cumulative incidence of any grade cGVHD was 9.2% and 9% in children and 5.5% and 13% in adults, with 5% moderate/severe/extensive cGVHD at 10 years. The 10y OS and GFRS for pediatric and adult patients in SAA was 93% (95% CI, 90-95%) & 83% (95%CI, 79-86%) and 78% (95%CI, 74-82%) & 68% (95%CI, 63-71%), whilst in IBMF 86 and 70% in children and 48 and 39% in adults, respectively. With FCC, 10y OS was 94% (95% CI, 89-97, children) and 79% (95% CI, 73-84, adults), whilst 10y GFRS was 83% and 70% respectively. FCC was statistically superior to other conditioning regimens for OS and GFRS, especially in adults (HR 0.67, p=0.029) vs pediatric (HR 0.52, p =0.070): Adults, HR 0.75, p=0.04 vs pediatric, HR 0.97, p=0.9). Age impacted OS in adults, HR 1.03, p<0.0005 (OS in18-39y, 85% vs 40-59y, 73% vs >60y 45%). Donor type did not influence OS; BM was superior only in children, both in SAA and IBMF: SAA (BM 95% vs PB 88%, P=0.01, HR 0.39) and IBMF (BM 90% vs PB 74%, P=0.009, HR 0.38). HCT-CI and Karnofsky performance score (KPS) impacted survival outcome in all age categories. FCC conditioning (OS: HR 0.35, p=0.034; GFRS, HR 0.49, p=0.01) and stem cell source (HR 0.41, p=0.033; HR 0.56, p=0.02) retained significance at multivariate analysis in children with SAA for both OS & GFRS, whilst advancing age (40-59 yrs, HR 1.96, p=0.002; >60 yrs, HR 3.25, p=0.0005) and KPS (<80, HR 1.99, P=0.005) impacted OS in adults. GFRS was impacted by FCC (>18y, HR 0.66, P=0.01) and by donor type (unrelated, <18y, HR 2.1, p=0.02 & >18y, HR 1.5, p=0.02) across the whole cohort of SAA.Conclusion: This is the largest report of BMF patients transplanted using a uniform alemtuzumab-based regimen, with excellent 10-year survival, low rates of graft failure and GVHD in both SAA and IBMF. The added benefit of BM as a stem cell source was evident in children; future efforts in the adult cohort should be directed toward improving outcomes in those >60yrs. Excellent OS and GFRS indicate alemtuzumab should be recommended in conditioning for all BMF syndromes.

Background Patient ethnicity has been correlated with different outcomes after haematopoietic cell transplantation (HCT), with patients from minority ethnic backgrounds reported to have worse outcomes compared with White patients. To date, studies have been predominantly done in the USA, where health-care models are different to many European countries, including the UK. We aimed to evaluate the impact of patient-reported ethnicity on autologous and allogeneic HCT outcomes in the UK. Methods In this retrospective cohort study, patients who had autologous or allogeneic HCT between Jan 1, 2009, and Dec 31, 2019, and were registered in the British Society of Blood and Marrow Transplantation and Cellular Therapy patient registry were analysed as full cohorts and as separate adult (>= 18 years) and paediatric (0-179 years) cohorts. Patient ethnicity was self-defined and grouped into four broad categories: Asian, Black, Other, and White. The outcome was 5-year overall survival, with overall survival defined as the time from transplantation to death from any cause. Findings 20 119 first autologous HCTs and 13 978 first allogeneic HCTs were analysed. Median times to follow-up were 60 months (IQR 35-89) for patients receiving autologous HCT and 32 months (10-68) for patients receiving allogeneic HCT. 5-year overall survival for the full allogeneic HCT cohort was 55% (95% CI 51-58). After adjustment for prognostic factors, Asian patients undergoing allogeneic HCT (n=1081) had significantly worse 5-year overall survival (hazard ratio [HR] 116 [95% CI 103-130], p=0012) than White patients (n=11 705). Differences in overall survival between White (n=1489) and Asian patients (n=384) were most pronounced in paediatric patients (HR 167 [95% CI 128-219], p=000018). In the autologous HCT cohort, there were no associations between ethnicity and 5-year overall survival. Interpretation This large UK-based analysis suggests significant variation in outcomes after allogeneic HCT between patients of different ethnicities. The causes are unclear, and further research to elucidate and improve these health inequalities is warranted. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Nutritional prehabilitation may improve haematopoietic cell transplantation (HCT) outcomes, although little evidence exists. The present study aimed to understand healthcare professional (HCP) perceptions of prehabilitation and nutritional care pre-HCT in UK centres. METHODS:An anonymous online survey (developed and refined via content experts and piloting) was administered via email to multidisciplinary HCPs in 39 UK adult centres, between July 2021 and June 2022. Data are presented as proportions of responses. Routine provision denotes that care was provided >70% of time. RESULTS:Seventy-seven percent (n = 66) of HCPs, representing 61.5% (n = 24) of UK adult HCT centres, responded. All HCPs supported prehabilitation, proposing feasible implementation between induction chemotherapy (60.4%; n = 40) and first HCT clinic (83.3%; n = 55). Only 12.5% (n = 3) of centres had a dedicated prehabilitation service. Nutrition (87.9%; n = 58), emotional wellbeing (92.4%; n = 61) and exercise (81.8%; n = 54) were considered very important constituents. HCPs within half of the HCT centres (n = 12 centres) reported routine use of nutrition screening pre-HCT with a validated tool; 66.7% of HCPs (n = 36) reported using the malnutrition universal screening tool (MUST). Sixty-two percent (n = 41) of HCPs reported those at risk, received nutritional assessments, predominantly by dietitians (91.6%; n = 22) using the dietetic care process (58.3%; n = 14). Body mass index (BMI) was the most frequently reported body composition measure used by HCPs (70.2%, n = 33). Of 59 respondents, non-dietitians most routinely provided dietary advice pre-HCT (82.4%; n = 28 vs. 68%; n = 17, p = 0.2); including high-energy/protein/fat and neutropenic diet advice. Prophylactic enteral feeding pre-HCT was rare, indicated by low BMI and significant unintentional weight loss. Just under half (n = 25 of 59, 42.4%) HCPs reported exercise advice was given routinely pre-HCT. CONCLUSIONS:Nutrition and prehabilitation pre-HCT are considered important and deliverable by HCPs, but current provision in UK centres is limited and inconsistent.

From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers' performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013-2016. A second phase was delivered in July 2021 covering 2015-2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this 'work in progress', as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.