329 results on '"Snowden, JA"'
Search Results
2. Collection of hematopoietic stem cells from patients with autoimmune diseases
- Author
-
Burt, RK, Fassas, A, Snowden, JA, van Laar, JM, Kozak, T, Wulffraat, NM, Nash, RA, Dunbar, CE, Arnold, R, Prentice, G, Bingham, S, Marmont, AM, and McSweeney, PA
- Published
- 2001
- Full Text
- View/download PDF
3. Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide
- Author
-
Snowden, JA, Hill, GR, Hunt, P, Carnoutsos, S, Spearing, RL, Espiner, E, and Hart, DNJ
- Published
- 2000
- Full Text
- View/download PDF
4. Autologous haematopoietic stem cell transplants for autoimmune disease – feasibility and transplant-related mortality
- Author
-
Tyndall, A, Fassas, A, Passweg, J, Ruiz de Elvira, C, Attal, M, Brooks, P, Black, C, Durez, P, Finke, J, Forman, S, Fouillard, L, Furst, D, Holmes, JA, Joske, D, Jouet, JP, Kötter, I, Locatelli, F, Prentice, HG, Marmont, AM, McSweeney, P, Musso, M, Peter, HH, Snowden, JA, Sullivan, K, Tichelli, A, Vavriec, J, Wulffraat, NM, Schmitz, N, and Gratwohl, A
- Published
- 1999
- Full Text
- View/download PDF
5. A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis
- Author
-
Snowden, JA, Biggs, JC, Milliken, ST, Fuller, A, Staniforth, D, Passuello, F, Renwick, J, and Brooks, PM
- Published
- 1998
- Full Text
- View/download PDF
6. Prolonged remission of longstanding systemic lupus erythematosus after autologous bone marrow transplant for non-Hodgkin’s lymphoma
- Author
-
Snowden, JA, Patton, WN, O’Donnell, JL, Hannah, EE, and Hart, DNJ
- Published
- 1997
- Full Text
- View/download PDF
7. Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis.
- Author
-
Das, J, Snowden, JA, Burman, J, Freedman, MS, Atkins, H, Bowman, M, Burt, RK, Saccardi, R, Innocenti, C, Mistry, S, Laud, PJ, Jessop, H, and Sharrack, B
- Subjects
- *
HEMATOPOIETIC stem cell transplantation , *MAGNETIC resonance imaging , *MULTIPLE sclerosis - Abstract
Background: Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with 'aggressive' MS is yet to be established. Objectives: The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with 'aggressive' MS. Methods: All patients with 'aggressive' MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated. Results: Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1–20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5–9.5). After a median follow-up of 30 (12–118) months, the median EDSS score improved to 2.0 (0–6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans. Conclusion: AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with 'aggressive' MS. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
8. Allogeneic bone marrow transplantation from a donor with severe active rheumatoid arthritis not resulting in adoptive transfer of disease to recipient
- Author
-
Snowden, JA, Atkinson, K, Kearney, P, Brooks, P, and Biggs, JC
- Published
- 1997
- Full Text
- View/download PDF
9. Human parainfluenza type 4 infection: a case report highlighting pathogenicity and difficulties in rapid diagnosis in the post-transplant setting
- Author
-
Miall, F, Rye, A, Fraser, M, Hunter, A, and Snowden, JA
- Published
- 2002
- Full Text
- View/download PDF
10. Allogeneic PBPC transplantation: an effect on incidence and distribution of chronic graft-versus-host disease without long-term survival benefit?
- Author
-
Snowden, JA, Nivison-Smith, I, Atkinson, K, Fay, K, Concannon, A, Dodds, A, Milliken, S, and Biggs, J
- Published
- 2000
- Full Text
- View/download PDF
11. Autologous blood stem cell transplantation for autoimmune diseases
- Author
-
Snowden, JA, Biggs, JC, and Brooks, PM
- Published
- 1996
- Full Text
- View/download PDF
12. Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.
- Author
-
Atsuta Y, Baldomero H, Neumann D, Sureda A, DeVos JD, Iida M, Karduss A, Purtill D, Elhaddad AM, Bazuaye NG, Bonfim C, De la Camara R, Chaudhri NA, Ciceri F, Correa C, Frutos C, Galeano S, Garderet L, Gonzalez-Ramella O, Greco R, Hamad N, Hazenberg MD, Horowitz MM, Kalwak K, Ko BS, Kodera Y, Koh MB, Liu K, McLornan DP, Moon JH, Neven B, Okamoto S, Pasquini MC, Passweg JR, Paulson K, Rondelli D, Ruggeri A, Seber A, Snowden JA, Srivastava A, Szer J, Weisdorf D, Worel N, Greinix H, Saber W, Aljurf M, and Niederwieser D
- Subjects
- Humans, Health Services Accessibility, Tissue Donors supply & distribution, Global Health, Registries, Hematopoietic Stem Cell Transplantation methods, Unrelated Donors
- Abstract
Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (6 World Health Organization regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT numbers increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA-identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/10 million population was observed for autologous HCT (correlation coefficient [r]=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation was detected from related donors (r=0.48 for HLA-identical sibling; r=0.45 for other). The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.
- Published
- 2024
- Full Text
- View/download PDF
13. Adenovirus infections after allogeneic hematopoietic cell transplantation in children and adults: a study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.
- Author
-
Styczynski J, Tridello G, Knelange N, Wendel L, Ljungman P, Mikulska M, Gil L, Cesaro S, Averbuch D, von dem Borne P, Xhaard A, Mielke S, Neven B, Snowden JA, Dalle JH, Rubio MT, Crawley C, Maertens J, Kuball J, Chevallier P, Michel G, Gabriel M, Burns D, Wynn RF, Renard C, Blijlevens N, Jubert C, Gedde-Dahl T, Collin M, Labussiere-Wallet H, Kalwak K, Broers AEC, Yakoub-Agha I, Itäla-Remes M, and de la Camara R
- Subjects
- Humans, Child, Adult, Male, Female, Adolescent, Child, Preschool, Middle Aged, Infant, Transplantation, Homologous, Risk Factors, Young Adult, Europe, Aged, Hematopoietic Stem Cell Transplantation adverse effects, Adenoviridae Infections etiology, Adenoviridae Infections mortality
- Abstract
The objective of the study was the analysis of clinical types, outcomes, and risk factors associated with the outcome of adenovirus (ADV) infection, in children and adults after allo-HCT. A total number of 2529 patients (43.9% children; 56.1% adults) transplanted between 2000 and 2022 reported to the EBMT database with diagnosis of ADV infection were analyzed. ADV infection manifested mainly as viremia (62.6%) or gastrointestinal infection (17.9%). The risk of 1-year mortality was higher in adults (p = 0.0001), and in patients with ADV infection developing before day +100 (p < 0.0001). The 100-day overall survival after diagnosis of ADV infections was 79.2% in children and 71.9% in adults (p < 0.0001). Factors contributing to increased risk of death by day +100 in multivariate analysis, in children: CMV seropositivity of donor and/or recipient (p = 0.02), and Lansky/Karnofsky score <90 (p < 0.0001), while in adults: type of ADV infection (viremia or pneumonia vs gastrointestinal infection) (p = 0.0004), second or higher HCT (p = 0.0003), and shorter time from allo-HCT to ADV infection (p = 0.003). In conclusion, we have shown that in patients infected with ADV, short-term survival is better in children than adults. Factors directly related to ADV infection (time, clinical type) contribute to mortality in adults, while pre-transplant factors (CMV serostatus, Lansky/Karnofsky score) contribute to mortality in children., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
14. Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial.
- Author
-
Cook G, Ashcroft AJ, Senior E, Olivier C, Hockaday A, Richards J, Cavenagh JD, Snowden JA, Drayson MT, de Tute R, Roberts L, Owen RG, Yong K, Garg M, Boyd K, Sati H, Gillson S, Cook M, Cairns DA, and Parrish C
- Abstract
Background: The efficacy of consolidation and maintenance in the context of salvage autologous haematopoietic stem-cell transplantation (HSCT) for relapsed multiple myeloma remains unclear. We aimed to assess whether consolidation after salvage autologous HSCT, using ixazomib, thalidomide, and dexamethasone, followed by maintenance with single agent ixazomib is superior to observation., Methods: This is an interim analysis of Myeloma XII (ACCorD; referred to as ACCorD hereafter), an open-label, randomised, controlled, phase 3 trial done at 79 hospitals in the UK. Eligible patients were aged 18 years or older, had relapsed multiple myeloma with measurable disease, an ECOG performance status of 2 or less with adequate renal, hepatobiliary, pulmonary, and cardiac function, and required treatment for first progressive disease occurring at least 12 months after first autologous HSCT. In a first randomisation, patients were assigned (1:1) to receive either conventional autologous HSCT with melphalan or augmented autologous HSCT with melphalan and ixazomib. In the second randomisation, reported here, patients were assigned (1:1) to consolidation using ixazomib, thalidomide, and dexamethasone (oral ixazomib 4 mg per day on days 1, 8, and 15, oral thalidomide 100 mg per day on days 1-28, and oral dexamethasone 40 mg per day on days 1, 8, 15 and 22 of 28-day cycles), followed by maintenance with single agent ixazomib (oral ixazomib 4 mg per day on days 1, 8, and 15 of 28-day cycles until disease progression or intolerance), or observation. The primary endpoint was progression-free survival, analysed by intention-to-treat. Safety was analysed per-protocol. This study is registered with ISRCTN, ISRCTN10038996, and EudraCT, 2016-000905-35, and recruitment is complete., Findings: Between Dec 12, 2017, and April 21, 2023, 206 patients entered the second randomisation (103 in the consolidation and maintenance group and 103 in the observation group). This prespecified interim analysis (data cutoff April 21, 2023), was done at a median follow-up of 27 months (IQR 13-38). Median progression-free survival was 20 months (95% CI 15-29) in the consolidation and maintenance group and 13 months (11-18) in the observation group (hazard ratio 0·55 [95% CI 0·39-0·78]; p=0·0006). Serious adverse events were reported in 29 (32%) of 92 patients in the consolidation and maintenance group compared with seven (7%) of 103 patients in the observation group. The most common serious adverse events were infections and infestations in both the consolidation and maintenance group and the observation group. The most common grade 3, 4, or 5 adverse events for patients in the consolidation and maintenance group were upper respiratory infection (seven [8%] of 92 patients). No deaths in the consolidation and maintenance group were deemed treatment related., Interpretation: ACCorD provides evidence that an orally administered, deliverable, and tolerable post-salvage autologous HSCT treatment regimen can improve the durability of response for transplantation-eligible patients at first relapse. The findings are of relevance to patients who had durable disease control from autologous HSCT in the first line, representing a viable alternative to continuous parentally-administered relapse therapies., Funding: Cancer Research UK, Takeda Oncology., Competing Interests: Declaration of interests GC reports research funding from Janssen, Takeda Oncology, Amgen, and BMS/Celgene; and consultancy fees from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche, and BMS/Celgene. AJA reports speaker fees and participation on advisory boards for Janssen and participation on advisory boards for Takeda. ES reports receipt of unrestricted educational grants to his institution from Takeda Oncology, Celgene Corporation, Merck, Amgen, and Sanofi. CO reports receipt of unrestricted educational grants to her institution from Takeda Oncology, Celgene Corporation, Merck, Amgen, and Sanofi. AH reports receipt of unrestricted educational grants to his institution from Takeda Oncology, Celgene Corporation, Merck, Amgen, and Sanofi; and speaker fees from Abbvie. JR reports receipt of unrestricted educational grants to her institution from Takeda Oncology, Celgene Corporation, Merck, Amgen and Sanofi. JS reports speaker fees from Janssen, Jazz, Mallinckrodt, and Sanofi; participation on advisory boards for Medac and Vertex; and Independent Data Monitoring Committee membership for a Kiadis Pharma clinical trial. MG reports participation on advisory boards for Amgen, Sanofi, Celgene, Stemline therapeutics, Janssen, and Novartis; research grants from Janssen; speaker honoraria from Janssen, Amgen and Alnylam; and travel expenses to attend educational meetings from Novartis, Janssen, and Takeda. KB reports participation on advisory boards at Takeda, Janssen, and Celgene/BMS; speaker honoraria from Janssen, Sanofi, and Celgene/BMS; and travel expenses to attend educational meetings from Janssen, GSK, and Takeda. SG reports receipt of unrestricted educational grants to her institution from Takeda Oncology, Celgene Corporation, Merck, Amgen, and Sanofi. DAC reports receipt of unrestricted educational grants to his institution from Takeda Oncology, Celgene Corporation, Merck, Amgen, and Sanofi; payment to their institution for educational lectures from Janssen; participation on a Data Safety Monitoring Board for a multiple myeloma study; and personal payment for meeting attendance from European Myeloma Network, Rotterdam. LR is a patient and public contributor. CP reports speaker honoraria from Janssen, Amgen, and Novartis; and participation on advisory boards at Pfizer and Sanofi. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
15. The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases.
- Author
-
Brittain G, Roldan E, Alexander T, Saccardi R, Snowden JA, Sharrack B, and Greco R
- Subjects
- Humans, Nervous System Diseases therapy, Nervous System Diseases immunology, Receptors, Chimeric Antigen immunology, Immunotherapy, Adoptive methods, Immunotherapy, Adoptive adverse effects
- Abstract
Despite the use of 'high efficacy' disease-modifying therapies, disease activity and clinical progression of different immune-mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy-based therapy with a range of short- and long-term side-effects. Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of B-cell and other hematological malignancies, conferring long-term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early-phase trials of CAR-T therapies in immune-mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR-T therapy in other immune-mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long-term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR-T in such conditions. ANN NEUROL 2024;96:441-452., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2024
- Full Text
- View/download PDF
16. Patient engagement in hematopoietic stem cell transplantation and cell therapy: a survey by the EBMT patient engagement task force & transplantation complications working party.
- Author
-
Schoemans H, Burns LJ, Liptrott SJ, Murray J, Kenyon M, Barata A, Bolaños N, Scholl I, Hamilton B, Phelan R, Buchbinder D, Penack O, Moiseev I, Boreland W, Peczynski C, De Geest S, Sureda A, Snowden JA, Shaw B, Peric Z, and Kroeger N
- Subjects
- Humans, Male, Female, Cross-Sectional Studies, Surveys and Questionnaires, Middle Aged, Adult, Patient Reported Outcome Measures, Cell- and Tissue-Based Therapy methods, Hematopoietic Stem Cell Transplantation methods, Patient Participation
- Abstract
The EBMT (European Blood and Marrow Transplantation Society) aims to connect patients, the scientific community, and other stakeholders to improve hematopoietic stem cell transplantation and cellular therapy outcomes. We performed a cross-sectional online survey to understand the perceptions regarding Patient Reported Outcomes (PROs) and Patient Active Involvement in Research (PAIR) in over 800 stakeholders (n = 813). Patients (n = 278) and health care professionals (HCPs) (n = 351) were compared. We observed high openness for EBMT PRO collection (n = 680, 84.5% across stakeholders' groups; patients n = 256, 93.1% versus HCPs n = 273, 78.4% [p < 0.001]) and PAIR (n = 702, 87.3% across stakeholder groups; patients n = 256, 92.4% versus HCPs n = 296, 85.8% [p = 0.009]), with a significantly higher proportion of patients expressing interest compared to HCPs. Priority domains for PROs data-collection identified were the assessment of symptom experience, psychosocial and cognitive functioning. The most important issues for patients specifically were the data-collection of PROs reflecting cognitive function, the option of reporting data at home, the importance of identifying actionable targets to improve their recovery, and receiving feedback on their input when participating in research projects. Our multistakeholder approach suggests an added value to embracing patient engagement in the development of meaningful research and service design within the transplantation and cellular therapy community., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
17. ATG and other serotherapy in conditioning regimens for autologous HSCT in autoimmune diseases: a survey on behalf of the EBMT Autoimmune Diseases Working Party (ADWP).
- Author
-
Ismail A, Nitti R, Sharrack B, Badoglio M, Ambron P, Labopin M, Alexander T, Snowden JA, and Greco R
- Published
- 2024
- Full Text
- View/download PDF
18. Health professional attitudes and perceptions of prehabilitation and nutrition before haematopoietic cell transplantation.
- Author
-
Miller LJ, Halliday V, Snowden JA, Aithal GP, Lee J, and Greenfield DM
- Subjects
- Humans, United Kingdom, Surveys and Questionnaires, Male, Female, Adult, Preoperative Care methods, Health Personnel psychology, Health Personnel statistics & numerical data, Middle Aged, Nutritional Status, Nutrition Therapy methods, Preoperative Exercise, Hematopoietic Stem Cell Transplantation psychology, Attitude of Health Personnel
- Abstract
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., (© 2024 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)
- Published
- 2024
- Full Text
- View/download PDF
19. Correction: Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
- Author
-
Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
- Published
- 2024
- Full Text
- View/download PDF
20. Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).
- Author
-
Garderet L, Gras L, Koster L, Baaij L, Hamad N, Dsouza A, Estrada-Merly N, Hari P, Saber W, Cowan AJ, Iida M, Okamoto S, Takamatsu H, Mizuno S, Kawamura K, Kodera Y, Ko BS, Liam C, Ho KW, Goh AS, Tan SK, Elhaddad AM, Bazarbachi A, Chaudhry QUN, Alfar R, Bekadja MA, Benakli M, Ortiz CAF, Riva E, Galeano S, Bass F, Mian HS, McCurdy A, Wang FR, Meng L, Neumann D, Koh M, Snowden JA, Schönland S, McLornan DP, Hayden PJ, Sureda A, Greinix HT, Aljurf M, Atsuta Y, and Niederwieser D
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Adult, Registries, Treatment Outcome, Lenalidomide therapeutic use, Lenalidomide administration & dosage, Survival Rate, Multiple Myeloma therapy, Multiple Myeloma mortality, Hematopoietic Stem Cell Transplantation, Transplantation, Autologous
- Abstract
Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
21. Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?
- Author
-
Scheid C, Eikema DJ, van Gelder M, Salmenniemi U, Maertens J, Passweg J, Blaise D, Byrne JL, Kröger N, Sockel K, Chevallier P, Bourhis JH, Cornelissen JJ, Sengeloev H, Finke J, Snowden JA, Gedde-Dahl T, Cornillon J, Schanz U, Patel A, Koster L, de Wreede LC, Hayden P, Raj K, Drozd-Sokolowska J, Gurnari C, Onida F, McLornan DP, Robin M, and Yakoub-Agha I
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Prognosis, Adult, Neoplasm Staging, Treatment Outcome, Young Adult, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Hematopoietic Stem Cell Transplantation methods
- Abstract
Abstract: In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
22. Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
- Author
-
Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
- Subjects
- Humans, Middle Aged, Male, Female, Adult, Aged, Transplantation Conditioning methods, Transplantation, Homologous methods, Graft vs Host Disease mortality, Busulfan analogs & derivatives, Busulfan therapeutic use, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Hematopoietic Stem Cell Transplantation methods, Registries
- Abstract
We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39-0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41-1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38-0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39-0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24-0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28-1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
23. 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).
- Author
-
Sanchez-Guijo F, Vives J, Ruggeri A, Chabannon C, Corbacioglu S, Dolstra H, Farge D, Gagelmann N, Horgan C, Kuball J, Neven B, Rintala T, Rocha V, Sanchez-Ortega I, Snowden JA, Zwaginga JJ, Gnecchi M, and Sureda A
- Subjects
- Humans, Europe, Registries, Societies, Medical, Accreditation methods, Genetic Therapy methods, Cell- and Tissue-Based Therapy methods
- Abstract
Cell and gene therapy poses evolving challenges. The current article summarizes the discussions held by European Regional Committee of the International Society for Cell & Gene Therapy and the European Society for Blood and Marrow Transplantation (EBMT) on the current challenges in this field, focusing on the European setting. This article emphasizes the imperative assessment of real-world cell and gene therapy activity, advocating for expanded registries beyond hematopoietic transplantation and chimeric antigen receptor-T-cell therapy. Accreditation's role in ensuring standardized procedures, as exemplified by JACIE (The Joint Accreditation Committee of ISCT-Europe and EBMT), is crucial for safety. Access to commercial products and reimbursement variations among countries underscore the need for uniform access to advanced therapy medical products (ATMPs). Academic product development and point-of-care manufacturing face barriers to patient access. Hospital Exemption's potential, demonstrated by some initial experiences, may increase patient accessibility in individual situations. Regulatory challenges, including the ongoing European ATMPs legislation review, necessitate standardized criteria for Hospital Exemption and mandatory reporting within registries. Efforts to combat unproven therapies and fraud involve collaboration between scientific societies, regulatory bodies and patient groups. Finally, is important to highlight the vital role of education and workforce development in meeting the escalating demand for specialized professionals in the ATMP field. Collaboration among scientific societies, academic institutions, industry, regulatory bodies and patient groups is crucial for overcoming all these challenges to increase gene and cell therapy activity in Europe., Competing Interests: Declaration of Competing Interest FSG, JV, DF, JJZ and MG are members of the International Society for Cellular Therapy (ISCT-EU) Executive Committee. AR, CC, SC, HD, NG, CH, JHEK, BN, TR, ISG, JAS and AS are members of European Society for Blood and Marrow Transplantation (EBMT) executive committee or working groups representatives. FSG has received research support from Novartis, Gilead. Honoraria from Novartis, Gilead, Pfizer, BMS-Celgene and Pierre-Fabré. CC has received honoraria (personal and institutional) and travel support from Bellicum Pharmaceuticals, BMS, Jazz Pharmaceuticals, Kite / Gilead, Novartis and Sanofi SA as a compensation for speaker's bureau and advisory boards. JK was shareholder of Gadeta and is inventor on multiple patents dealing with engineered immune cells, and has received research support from Novartis, Milteny Biotech and Gadeta. JAS has received consultancy honoraria from Kiadis, Medac, Vertex and Jazz. AS has received research support from Takeda and honoraria from Takeda, BMS/Celgene, MSD, Novartis, Gilead Kite, Sanofi, Pierre Fabre, Janssen and Jazz Pharmaceuticals. All other authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. European flow cytometry quality assurance guidelines for the diagnosis of primary immune deficiencies and assessment of immune reconstitution following B cell depletion therapies and transplantation.
- Author
-
Kelleher P, Greathead L, Whitby L, Brando B, Barnett D, Bloxham D, deTute R, Dunlop A, Farren T, Francis S, Payne D, Scott S, Snowden JA, Sorour Y, Stansfield E, Virgo P, and Whitby A
- Abstract
Over the last 15 years activity of diagnostic flow cytometry services have evolved from monitoring of CD4 T cell subsets in HIV-1 infection to screening for primary and secondary immune deficiencies syndromes and assessment of immune constitution following B cell depleting therapy and transplantation. Changes in laboratory activity in high income countries have been driven by initiation of anti-retroviral therapy (ART) in HIV-1 regardless of CD4 T cell counts, increasing recognition of primary immune deficiency syndromes and the wider application of B cell depleting therapy and transplantation in clinical practice. Laboratories should use their experience in standardization and quality assurance of CD4 T cell counting in HIV-1 infection to provide immune monitoring services to patients with primary and secondary immune deficiencies. Assessment of immune reconstitution post B cell depleting agents and transplantation can also draw on the expertise acquired by flow cytometry laboratories for detection of CD34 stem cell and assessment of MRD in hematological malignancies. This guideline provides recommendations for clinical laboratories on providing flow cytometry services in screening for immune deficiencies and its emerging role immune reconstitution after B cell targeting therapies and transplantation., (© 2024 The Author(s). Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)
- Published
- 2024
- Full Text
- View/download PDF
25. Results from UKALL60+, a phase 2 study in older patients with untreated acute lymphoblastic leukemia.
- Author
-
Patel B, Kirkwood AA, Rowntree CJ, Alapi KZ, Barretta E, Clifton-Hadley L, Creasey T, Lee S, Marks DI, Moorman AV, Morley N, Patrick P, Rana Z, Rijneveld A, Snowden JA, and Fielding AK
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
- Full Text
- View/download PDF
26. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial.
- Author
-
Goodyear CS, Patel A, Barnes E, Willicombe M, Siebert S, de Silva TI, Snowden JA, Lim SH, Bowden SJ, Billingham L, Richter A, Carroll M, Carr EJ, Beale R, Rea D, Parry H, Pirrie S, Lim Z, Satsangi J, Dunachie SJ, Cook G, Miller P, Basu N, Gilmour A, Hodgkins AM, Evans L, Hughes A, Longet S, Meacham G, Yong KL, A'Hearne MJ, Koh MBC, Burns SO, Orchard K, Paterson C, McIlroy G, Murray SM, Thomson T, Dimitriadis S, Goulston L, Miller S, Keillor V, Prendecki M, Thomas D, Kirkham A, McInnes IB, and Kearns P
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Antibodies, Viral blood, Prospective Studies, Immunization, Secondary, 2019-nCoV Vaccine mRNA-1273 immunology, Adult, T-Lymphocytes immunology, United Kingdom, ChAdOx1 nCoV-19 immunology, COVID-19 prevention & control, COVID-19 immunology, Immunocompromised Host immunology, SARS-CoV-2 immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, Immunogenicity, Vaccine, BNT162 Vaccine immunology, BNT162 Vaccine administration & dosage
- Abstract
Background: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies., Methods: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete., Findings: Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3-7990·0] compared with median 11·5 AU/mL [0·4-63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related., Interpretation: A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose., Funding: Medical Research Council, Blood Cancer UK., Competing Interests: Declaration of interests DR reports research funding from Roche, Biotheranostics, RNA diagnostics, and Celgene; and honoraria or consultancy fees from Novartis, Pfizer, Lily, Roche, and AstraZeneca–Diiachi Sankyo. EB reports research funding from Vaccitech; consultancy fees from Roche, Vaccitech, and AstraZeneca; and holds patents in ChAdOx1 hepatitis B virus and hepatitis C virus vaccines. HP reports honoraria from AstraZeneca. IBM reports research funding or consultancy fees from AbbVie, Amgen, Bristol-Myers Squibb (BMS), Causeway Therapeutics Cabaletta, Eli Lilly, Evelo Biosciences, Gilead, GSK, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB; consultancy fees from AbbVie, Amgen, BMS, Causeway Therapeutics Cabaletta, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB; and is on the board of directors of Evelo Biosciences. KO reports royalties to his institution from Telix Pharmaceuticals for Radiolabelled anti-CD66 antibody; consulting fees from Sanofi and Takeda; and stocks in GSK. KLY reports honoraria from Sanofi Genzyme, Takeda, and Amgen; support for meeting attendance from Takeda; and participation on a trial steering committee for Sanofi and an advisory board for Janssen. MJA reports research funding from Pfizer. MW reports research funding from Oxford Immunotech. MBCK reports honoraria from Gilead. MC reports consultancy fees from VacciTech. PK reports research funding from Bayer; and consultancy fees from AstraZeneca, Merck, and BMS. SM reports stock options in TCB BioPharm. SHL reports honoraria from AstraZeneca. SS reports research funding from Amgen, Boehringer-Ingelheim, BMS, GSK, Janssen, and UCB; and consultancy fees or honoraria from AbbVie, Eli Lilly, GSK, Janssen, and UCB. SOB reports research funding from CSL Behring; and consultancy fees, honoraria, or support for attending meetings from GSK, Baxalta US, and Biotest. JAS reports honoraria from Novartis and Gilead; advisory board fees from the Kiadis clinical trial, Medac, and NHS England National Specialised Commissioning Clinical Reference Group for Blood and Marrow Transplantation; and unpaid roles as President of British Society of Blood and Marrow Transplantation and Cellular Therapy, secretary of the European Society for Blood and Marrow Transplantation and as a board member of the British Society of Haematology. SJD is a Scientific Advisor to the Scottish Parliament on COVID-19 for which she receives a fee. All other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
27. The role of registries in hematological disorders.
- Author
-
Baldomero H, Neumann D, Hamad N, Atsuta Y, Sureda A, Iida M, Karduss A, Elhaddad AM, Bazuaye NG, Bonfim C, Camara R, Chaudhri NA, Ciceri F, Correa C, Frutos C, Galeano S, Garderet L, Greco R, Jaimovich G, Kodera Y, Koh MB, Liu K, Ljungman P, McLornan DP, Nair G, Okamoto S, Pasquini MC, Passweg J, Paulson K, Ruggeri A, Seber A, Snowden JA, Srivastava A, Worel N, Saber W, Rondelli D, Aljurf M, and Niederwieser D
- Subjects
- Humans, Registries, Hematopoietic Stem Cell Transplantation, Hematologic Diseases therapy
- Abstract
Hematopoietic cell transplantation (HCT) was developed more than 65 years ago to treat malignant blood disorders and irreversible bone marrow failures, with the aim of replacing a diseased hematopoietic system with a healthy one (allogeneic HCT). Decades later, the procedure was adapted to apply maximal chemotherapy or radiotherapy, which would result in bone marrow failure, but could be remedied by an infusion of a patient's own cryopreserved bone marrow (autologous HCT). Both treatments are high-risk and complex, especially during the initial phases. However, concerted efforts, vision, and collaboration between physicians and centers worldwide have resulted in HCT becoming a standard of care for many hematological disorders with progressive improvements in outcomes. Registries and the collaboration of societies worldwide have enabled the delivery of this curative therapy to many patients with fatal hematological diseases. More than 1.5 million HCT were performed between 1957 and 2019, and activity is continuously increasing worldwide., Competing Interests: Declaration of cometing interest NH reports advisory board honoraria from Janssen, Novartis, Takeda, Abbvie, Roche, Astellas and Bigene. YA reports consulting fees from JCR Pharmaceuticals Co., Ltd. and Kyowa Kirin Co., Ltd., lecture fees from Otsuka Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd., Novartis Pharma KK, AbbVie GK, and honorarium from Meiji Seika Pharma Co., Ltd. MI is affiliated with the Department of Promotion for Blood and Marrow Transplantation at the Aichi Medical University School of Medicine, and the department is endowed by AIR WATER INC., Clinigen K.K., and JCR Pharmaceuticals Co., Ltd. CF reports support for attending meetings from Casa Bollar and support for attending meetings and travel from Diaz Gill Lab and Prosalud. LG reports consulting fees from Sanofi, Janssen Pharmaceutical, Bristol Myers Squibb, and GlaxoSmithKline Pharmaceuticals and support for attending meetings and travel from Pfizer and Sanofi. KK reports honoraria from Pierre Fabre, Medac, and Novartis. J Snowden reports consulting fees from Jazz Pharmaceuticals, Medac Pharma, Vertex Pharmaceuticals, and participation in a Data Safety Monitoring Board in Kiadis Pharma. NW reports consulting and speakers fees from BMS Celgene, Kite Gilead, Miltenyi BioTec, Novartis, Piere Fabre and Therakos Mallinckrodt. The other authors report no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
28. Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR-T activity continues to grow; transplant activity has slowed: a report from the EBMT.
- Author
-
Passweg JR, Baldomero H, Ciceri F, de la Cámara R, Glass B, Greco R, Hazenberg MD, Kalwak K, McLornan DP, Neven B, Perić Z, Risitano AM, Ruggeri A, Snowden JA, and Sureda A
- Subjects
- Humans, Europe, Male, Female, Hematopoietic Stem Cell Transplantation methods
- Abstract
In 2022, 46,143 HCT (19,011 (41.2%) allogeneic and 27,132 (58.8%) autologous) in 41,854 patients were reported by 689 European centers. 4329 patients received advanced cellular therapies, 3205 of which were CAR-T. An additional 2854 patients received DLI. Changes compared to the previous year were an increase in CAR-T treatments (+27%) and decrease in allogeneic (-4.0%) and autologous HCT (-1.7%). Main indications for allogeneic HCT were myeloid malignancies (10,433; 58.4%), lymphoid malignancies (4,674; 26.2%) and non-malignant disorders (2572; 14.4%). Main indications for autologous HCT were lymphomas (7897; 32.9%), PCD (13,694; 57.1%) and solid tumors (1593; 6.6%). In allogeneic HCT, use of sibling donors decreased by -7.7%, haploidentical donors by -6.3% and unrelated donors by -0.9%. Overall cord blood HCT decreased by -16.0%. Use of allogeneic, and to a lesser degree autologous HCT, decreased for lymphoid malignancies likely reflecting availability of new treatment modalities, including small molecules, bispecific antibodies, and CAR-T cells. Pediatric HCT activity remains stable (+0.3%) with differences between allogeneic and autologous HCT. Use of CAR-T continues to increase and reached a cumulative total of 9039 patients treated with wide differences across European countries. After many years of continuous growth, increase in application of HCT seems to have slowed down., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
29. Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group.
- Author
-
Alexander T, Tassy N, Domenech A, Kramer E, Jessop H, Kenyon M, Sharrack B, Saccardi R, Bolanos N, Snowden JA, and Greco R
- Abstract
Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT., Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment., Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT., Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey., Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders., Competing Interests: This work was led and supported by the Autoimmune Diseases Working Party, Nurses Group, and Patient Advocacy Committee of the EBMT. The EBMT provided resources via the working party, data office, and registry. Other than EBMT support, there is no funding body supporting this work, commercial or otherwise. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
30. Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial.
- Author
-
Lindsay JO, Hind D, Swaby L, Berntsson H, Bradburn M, Bannur C U, Byrne J, Clarke C, Desoysa L, Dickins B, Din S, Emsley R, Foulds GA, Gribben J, Hawkey C, Irving PM, Kazmi M, Lee E, Loban A, Lobo A, Mahida Y, Moran GW, Papaioannou D, Parkes M, Peniket A, Pockley AG, Satsangi J, Subramanian S, Travis S, Turton E, Uttenthal B, Rutella S, and Snowden JA
- Subjects
- Adult, Humans, Standard of Care, State Medicine, Ulcer etiology, Treatment Outcome, Cyclophosphamide adverse effects, Granulocyte Colony-Stimulating Factor therapeutic use, Crohn Disease drug therapy, Hematopoietic Stem Cell Transplantation adverse effects, Renal Insufficiency
- Abstract
Background: A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population., Methods: This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m
2 with granulocyte colony-stimulating factor (G-CSF) 5 μg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2 , cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440., Findings: Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure., Interpretation: Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease., Funding: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership., Competing Interests: Declaration of interests JOL reports grants for investigator-initiated research from the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation research grant for the current project, AbbVie, Gilead Sciences, Takeda UK, and Shire; honoraria for consulting or advisory boards from AbbVie, Allergan, Atlantic Healthcare, Bristol Meyers Squibb, Celgene, Celltrion, Lilly, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, GlaxoSmithKline, Janssen, MSD, Napp Pharmaceuticals, Norgine BV, Pfizer, Shire, Takeda UK, and Vifor Pharma Management; honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Bristol Meyers Squibb, Ferring Pharmaceuticals, Galapagos NV, Janssen, Norgine BV, Pfizer, Shire, Takeda UK, and Cornerstone Healthcare Group; and support for attending meetings, travel, or both from AbbVie, Takeda UK, MSD, Ferring Pharmaceuticals, and Janssen, outside the submitted work. DH reports part funding for salary through the NIHR Efficacy and Mechanism Evaluation research grant for this project. RE reports participation in the NIHR Clinical Trials Unit Standing Advisory Committee (2020 to present), and the Health Technology Assessment Clinical Evaluation and Trials Committee (2017–21). LD reports various NIHR grants, none of which relate to Crohn's disease or investigate treatments similar to those in ASTIClite. SD reports salary funding from NHS Research Scotland via NHS Lothian to support clinical trial work; grants from the Edinburgh & Lothian Health Foundations Award, the Pathological Society of Great Britain & Northern Ireland, Helmsley Charitable Trust–Gut Cell Atlas Normal and Crohn's Disease, and Helmsley Charitable Trust CDTREAT and BIOPIC studies; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Jannsen, Ferring, Takeda, and AbbVie; and support for attending meetings, travel, or both from Janssen, Dr Falk Symposium, and AbbVie. SD also reports participation on a data safety monitoring board or advisory board for AbbVie and MHRA; and leadership or fiduciary role on other board, society, committee, or advocacy groups for the British Society of Gastroenterology, the Royal College of Physicians of Edinburgh, and the Scottish Government. JG reports consulting fees from AbbVie, AstraZeneca, Bristol Meyers Squibb, Gilead Sciences, Janssen, MorphoSys AG, and Novartis AG; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Bristol Meyers Squibb, Gilead Sciences, and Janssen; and participation on a data safety monitoring board or advisory board for AstraZeneca, outside the submitted work. PI reports grants or contracts from MSD, Takeda UK, Celltrion, and Pfizer; consulting fees from Bristol Meyers Squibb, AbbVie, Arena, Boehringer-Ingelheim, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Bristol Meyers Squibb, Celgene, Celltrion, Dr Falk Pharma GmbH, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, MSD, Janssen, Pfizer, Takeda UK, Tillotts Pharma AG, Sapphire Medical, Sandoz, Shire, and Warner Chilcott UK, outside the submitted work. EL reports various other NIHR grants, none of which relate to Crohn's disease or investigate treatments similar to those in ASTIClite; and participation in two data monitoring and ethics committees and two trial steering committees for NIHR trials outside the submitted work, none of which relate to Crohn's disease. MP reports grants or contracts from Pfizer, Gilead Sciences, and Crohn's & Colitis UK, outside the submitted work; and a leadership role as Director of Cambridge Biomedical Research Centre, outside the submitted work (2020 to present). AL reports consulting fees from Takeda UK, Vifor Pharma Management, Janssen, and PredictImmune; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda UK, Janssen, and Celltrion; support for attending meetings, travel, or both from Janssen, Tillotts Pharma AG, Takeda UK, and Vifor Pharma Management; and is Director of the non-executive IBD Registry Board. AGP reports being the Chief Executive Officer of multimmune GmbH, Chief Scientific Officer of Alphageneron Pharmaceuticals, and a member of the scientific advisory board of Cytomos, none of which relate to Crohn's disease and all are outside the submitted work. SS reports grants or contracts from Crohn's & Colitis UK and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda UK, Janssen, AbbVie, Celltrion, Boehringer Ingelheim International GmbH, and Bristol Meyers Squibb, outside the submitted work; and participation on a data safety monitoring board or advisory board for Takeda UK, Janssen, AbbVie, Celltrion, Boehringer Ingelheim International GmbH, Bristol Meyers Squibb, and Vifor Pharma Management, outside the submitted work. JS reports grant funding for IBD research from the European Crohn's & Colitis Organization (ECCO), The Leona M and Harry B Helmsley Charitable Trust, Crohn's & Colitis UK, Crohn's & Colitis Foundation, Action Medical Research, the NIHR Efficacy and Mechanism Evaluation, European Commission FP-7, and Horizon 2020 programmes, outside the submitted work; and payment or honoraria for a lecture for the Falk Foundation, and a leadership role on the UK IBD Registry Management Board. ST reports grants or contracts from ECCO, the Leona M and Harry B Helmsley Charitable Trust, Ferring Pharmaceuticals, Janssen, Lilly, Pfizer, Takeda UK, and the Norman Collisson Charitable Trust; and consulting fees from ai4gi Joint Venture, Allergan, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim International GmbH, Bristol Meyers Squibb, Bühlmann Laboratories AG, Celgene, ChemoCentryx, Cosmo Pharmaceuticals NV, Enterome, Equillium, Ferring Pharmaceuticals, Genentech–Roche, Gilead Sciences, Glenmark Pharmaceuticals, Grünenthal, GlaxoSmithKline, Immunometabolism, Indigo Diabetes, Janssen, Lilly, Merck KGaA, Mestag Therapeutics, Novartis AG, Pfizer, PharmaVentures, Phesi, Satisfai Health, Sensyne Health, Sorriso, SynDermix, Synthon, Takeda UK, Topivert, UCB SA, Vertex Pharmaceuticals, VHsquared, and Vifor Pharma Management, outside the submitted work. ST also reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Biogen, Dr Falk Pharma GmbH, Ferring Pharmaceuticals, Janssen, Pfizer, Shire, Takeda UK, and UCB SA; payment for expert testimony from Cosmo; support for attending meetings, travel, or both from AbbVie, Amgen, Biogen, Dr Falk Pharma GmbH, Ferring Pharmaceuticals, Janssen, Pfizer, Shire, Takeda UK, and UCB SA; and participation on a data safety monitoring board or advisory board for Amgen, outside the submitted work. SR reports research funding from MacroGenics and Kura Oncology, outside the submitted work. BU reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for Gilead and Novartis; and support for attending meetings, travel, or both from Takeda and Gilead. JS reports support for the current work through a NIHR Efficacy and Mechanism Evaluation grant; consulting fees from Medac (not directly related to Crohn's disease); and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Jazz Pharmaceuticals, Mallinckrodt Pharmaceuticals, Janssen, Gilead Sciences, Vertex, and Actelion, none of which directly relate to Crohn's disease, outside the submitted work. JS also reports participation on the Kiadis Pharma trial Independent Data Monitoring Committee, which does not directly relate to Crohn's disease, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
31. Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT.
- Author
-
Gurnari C, Koster L, Baaij L, Heiblig M, Yakoub-Agha I, Collin M, Passweg J, Bulabois CE, Khan A, Loschi M, Carnevale-Schianca F, Crisà E, Caravelli D, Kuball J, Saraceni F, Olivieri A, Rambaldi A, Kulasekararaj AG, Hayden PJ, Badoglio M, Onida F, Scheid C, Franceschini F, Mekinian A, Savic S, Voso MT, Drozd-Sokolowska J, Snowden JA, Raj K, Alexander T, Robin M, Greco R, and McLornan DP
- Subjects
- Transplantation, Homologous, Humans, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes, Skin Diseases, Genetic
- Published
- 2024
- Full Text
- View/download PDF
32. Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation.
- Author
-
Pagliuca S, Kulasekararaj AG, Eikema DJ, Piepenbroek B, Iftikhar R, Satti TM, Griffin M, Laurino M, Kupesiz A, Bertrand Y, Fattizzo B, Yakoub-Agha I, Aljurf M, Corti P, Massaccesi E, Lioure B, Calabuig M, Klammer M, Unal E, Wu D, Chevallier P, Forcade E, Snowden JA, Ozdogu H, Risitano A, and De Latour RP
- Subjects
- Humans, Adult, Child, Androgens, Bone Marrow, Prospective Studies, Retrospective Studies, Bone Marrow Failure Disorders, Anemia, Aplastic therapy
- Abstract
Androgens represent the historical therapeutic backbone of bone marrow failure (BMF) syndromes. However, their role has rarely been analyzed in a prospective setting, and systematic and long-term data regarding their usage, effectiveness and toxicity in both acquired and inherited BMF are currently unavailable. Here, taking advantage of a unique disease-specific international dataset, we retrospectively analyzed the largest cohort so far of BMF patients who received androgens before or in the absence of an allogeneic hematopoietic cell transplantation (HCT), re-evaluating their current use in these disorders. We identified 274 patients across 82 European Society for Blood and Marrow Transplantation (EBMT) affiliated centers: 193 with acquired (median age 32 years) and 81 with inherited (median age 8 years) BMF. With a median duration of androgen treatment of 5.6 and 20 months, respectively, complete and partial remission rates at 3 months were 6% and 29% in acquired and 8% and 29% in inherited disorders. Five-year overall survival and failure-free survival (FFS) were respectively 63% and 23% in acquired and 78% and 14% in inherited BMF. Androgen initiation after second-line treatments for acquired BMF, and after >12 months post diagnosis for inherited BMF were identified as factors associated with improved FFS in multivariable analysis. Androgen use was associated with a manageable incidence of organ-specific toxicity, and low rates of solid and hematologic malignancies. Sub-analysis of transplant-related outcomes after exposure to these compounds showed probabilities of survival and complications similar to other transplanted BMF cohorts. This study delivers a unique opportunity to track androgen use in BMF syndromes and represents the basis for general recommendations on this category of therapeutics on behalf of the Severe Aplastic Anemia Working Party of the EBMT.
- Published
- 2024
- Full Text
- View/download PDF
33. Impact of minimal residual disease (MRD) in salvage autologous stem cell transplantation for relapsed myeloma: results from the NCRI Myeloma X (intensive) trial.
- Author
-
de Tute RM, Cook G, Cairns DA, Brown JM, Cavenagh J, Ashcroft AJ, Snowden JA, Yong K, Tholouli E, Jenner M, Hockaday A, Drayson MT, Morris TCM, Rawstron AC, and Owen RG
- Subjects
- Humans, Neoplasm Recurrence, Local, Neoplasm, Residual, Stem Cell Transplantation methods, Transplantation, Autologous, Clinical Trials as Topic, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
- Published
- 2024
- Full Text
- View/download PDF
34. Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee.
- Author
-
Greco R, Alexander T, Del Papa N, Müller F, Saccardi R, Sanchez-Guijo F, Schett G, Sharrack B, Snowden JA, Tarte K, Onida F, Sánchez-Ortega I, Burman J, Castilla Llorente C, Cervera R, Ciceri F, Doria A, Henes J, Lindsay J, Mackensen A, Muraro PA, Ricart E, Rovira M, Zuckerman T, Yakoub-Agha I, and Farge D
- Abstract
Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated., Competing Interests: RG discloses speaking honoraria from Biotest, Pfizer, Medac, Neovii and Magenta. TA received study support from Amgen, Janssen and honoraria from Neovii, GSK, Astra-Zeneca, Abbvie. FM received honoraria & travel support from BMS, Janssen, Gilead, Miltenyi, Novartis, Astra-Zeneca, Biontech, received research support from Gilead, and discloses advisory board from Biontech. JAS discloses consultancy for Vertex, Medac and Jazz, and advisory board from Kiadis. PA discloses study support by NIHR, payment for expert testimony by Pinsent Mason and Bugge Valentin and consulting to Cellerys AG. RS discloses speaking honoraria from Novartis and Gilead. CCL received travel support for attending meeting by Gilead and discloses consultancy for Nektar Therapeutics and Gilead. FSG received study support from Novartis and Gilead, speaking honoraria from Astra-Zeneca and travel support from Abbvie, Gilead and Pierre-Fabre. FO discloses speaking honoraria from Takeda, Medac, Kyowa Kirin, Menarini-Stemline, and travel support from Medac, Jazz and Janssen. JOL received study support from Abbvie, Gilead, Takeda, consultancy & honoraria from AbbVie, BMS, Celgene, Celtrion, Engytix, Ferring, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Pfizer, Shire, Takeda, travel support by Abbvie, Takeda, Celltrion. AM received study support from Kyverna, Miltenyi and honoraria from Miltenyi, and participated to advisory board from Century Therapeutics. RC discloses speaking honoraria from GSK, AstraZeneca, Werfen, Rubió, Eli-Lilly, Pfizer. IYA discloses speaking honoraria from Kite, Novartis and BMS. None of the mentioned conflicts of interest were related to financing of the content of this manuscript. The remaining authors have nothing to declare., (© 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
35. Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.
- Author
-
Brittain G, Petrie J, Duffy KEM, Glover R, Hullock K, Papaioannou D, Roldan E, Beecher C, Bursnall M, Ciccarelli O, Coles AJ, Cooper C, Giovannoni G, Gabriel I, Kazmi M, Kyriakou C, Nicholas R, Paling D, Peniket A, Scolding N, Silber E, de Silva T, Venneri A, Walters SJ, Young C, Muraro PA, Sharrack B, and Snowden JA
- Subjects
- Humans, Cladribine therapeutic use, Alemtuzumab therapeutic use, Transplantation, Autologous, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Humanized
- Abstract
Introduction: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS., Methods and Analysis: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs., Ethics and Dissemination: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences., Trial Registration Number: ISRCTN88667898., Competing Interests: Competing interests: GB, JP, KEMD, RG, KH, DPap, ER, CB, MG, OC, CC, GG, MK, CK, RN, DPal, AP, NS, ES, TdS, AV, SW, BS report no relevant competing interests. AC reports no relevant disclosures since 2017. RH reports attendance at paid advisory boards with Novartis, Biogen and Roche. CAY reports personal compensation for serving on scientific advisory boards, conference support or speaker honoraria from BMS, Biogen, Celgene, Cytokinetics, GW Pharmaceuticals, Novartis, Roche and Teva. Pharmaceuticals. PAM reports grants from National Institute of Health Research, non-financial support from National Institute of Health Research, grants from Benaroya Research Institute and National Institute of Allergy and Infectious Diseases of the National Institutes of Health, during the conduct of the study; personal fees from Jasper Therapeutics, personal fees from Magenta Therapeutics, personal fees from Rubius Therapeutics, outside the submitted work. JAS declares consultancy for Jazz, Medac, Vertex and Kiadis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
36. Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.
- Author
-
Duque-Afonso J, Finke J, Ngoya M, Galimard JE, Craddock C, Raj K, Bloor A, Nicholson E, Eder M, Kim O, Valerius T, Snowden JA, Tholouli E, Crawley C, Collin M, Wilson KMO, Gadisseur A, Protheroe R, Wagner-Drouet EM, Savani BN, Spyridonidis A, Ciceri F, Nagler A, and Mohty M
- Subjects
- Humans, Adult, Melphalan pharmacology, Melphalan therapeutic use, Carmustine, Thiotepa pharmacology, Thiotepa therapeutic use, Busulfan, Antineoplastic Combined Chemotherapy Protocols adverse effects, Transplantation Conditioning methods, Transplantation, Homologous adverse effects, Recurrence, Pathologic Complete Response, Alkylating Agents, Retrospective Studies, Leukemia, Myeloid, Acute, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology, Vidarabine analogs & derivatives
- Abstract
Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m
2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2 . We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT., (© 2023. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
37. Autologous hematopoietic stem cell transplantation for pediatric autoimmune neurologic disorders.
- Author
-
Kirgizov K, Burman J, Snowden JA, and Greco R
- Subjects
- Humans, Child, Autoimmune Diseases of the Nervous System therapy, Autoimmune Diseases of the Nervous System immunology, Neuromyelitis Optica therapy, Neuromyelitis Optica immunology, Pediatrics methods, Hematopoietic Stem Cell Transplantation methods, Transplantation, Autologous methods
- Abstract
Autologous hematopoietic stem cell transplantation (aHSCT) may be effective in carefully selected pediatric patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and chronic inflammatory demyelinating polyneuropathy (CIDP). aHSCT for pediatric MS (same as for adults) is performed to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Its therapeutic effect in MS relies on various mechanisms: (1) the immunosuppressive conditioning regimen prior to aHSCT was able to eradicate the autoreactive cells and (2) the regeneration/renewal of the immune system to reset the aberrant immune response against self-antigens. The aHSCT procedure includes the following different steps, as described in this chapter: patient selection through careful pretransplant screening, "wash-out" period from previous treatments, mobilization of hematopoietic stem cells (HSC), conditioning regimen, HSC infusion, and posttransplant monitoring for early and late complications. Moreover, specific aspects of pediatric population undergoing aHSCT are described. According to the available evidence, aHSCT appears to be safe in pediatric MS, obtaining disease control for a prolonged time after the procedure. A reasonable approach in this setting includes the application of less toxic treatments while reserving aHSCT procedure for patients with severe/refractory forms of the disease. The EBMT considers MS, NMO, and CIDP in pediatric patients within the category of the clinical option (CO), where candidates for aHSCT can be selected on the basis of careful consideration of individual case history in the multidisciplinary setting., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
38. Economics of hematopoietic stem cell transplant in immune-mediated neurologic autoimmune diseases.
- Author
-
Hughes SL, Prettyjohns MJ, Snowden JA, and Sharrack B
- Subjects
- Humans, Cost-Benefit Analysis, Autoimmune Diseases of the Nervous System economics, Autoimmune Diseases of the Nervous System therapy, Autoimmune Diseases of the Nervous System immunology, Hematopoietic Stem Cell Transplantation economics, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic procedure for autoimmune diseases which suppresses inflammation and resets the immune system, thereby halting disease activity and disability progression in treatment-resistant patients. This chapter reviews existing guidelines and health economic evaluations of AHSCT for multiple sclerosis (MS) and presents a cost-utility analysis from the UK NHS and personal social services perspective comparing AHSCT with disease-modifying therapies (DMTs) in patients with highly active relapsing-remitting MS (RRMS) based on the only published randomized controlled trial, "MIST," in this population. Over a 5-year time horizon, AHSCT was dominant (more effective and less costly) over the DMTs in MIST. At a threshold of £20,000 per QALY, there was a 100% probability that AHSCT was cost-effective. This result is explained by the high ongoing costs of DMTs compared with the up-front cost of AHSCT, combined with the high effectiveness of AHSCT. When compared with natalizumab, the result did not change; AHSCT remained dominant. These results support current guideline recommendations regarding AHSCT for highly active RRMS. The cost-effectiveness of AHSCT in progressive and aggressive MS and other immune-mediated neurologic diseases remains uncertain due to a lack of health economic analyses, reflecting the limited clinical evidence base., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
39. Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations.
- Author
-
Rejeski K, Subklewe M, Aljurf M, Bachy E, Balduzzi A, Barba P, Bruno B, Benjamin R, Carrabba MG, Chabannon C, Ciceri F, Corradini P, Delgado J, Di Blasi R, Greco R, Houot R, Iacoboni G, Jäger U, Kersten MJ, Mielke S, Nagler A, Onida F, Peric Z, Roddie C, Ruggeri A, Sánchez-Guijo F, Sánchez-Ortega I, Schneidawind D, Schubert ML, Snowden JA, Thieblemont C, Topp M, Zinzani PL, Gribben JG, Bonini C, Sureda A, and Yakoub-Agha I
- Subjects
- Consensus, Immunotherapy, Adoptive, Immunologic Factors, Hematopoietic Stem Cell Transplantation, Hematology
- Abstract
Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell-associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management., (© 2023 by The American Society of Hematology.)
- Published
- 2023
- Full Text
- View/download PDF
40. Implementation of the updated NICE haematological cancers (NG47) improving outcomes guidelines across Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) in England: a UK NEQAS LI survey.
- Author
-
Cartwright A, Snowden JA, Whitehouse H, Scott S, and Whitby L
- Subjects
- Humans, England, Surveys and Questionnaires, Diagnostic Services, Patient Care, Hematologic Neoplasms diagnosis, Hematologic Neoplasms therapy
- Abstract
Aims: Haematological malignancies represent a diverse group of diseases with complex diagnostic requirements. National Institute for Health and Care Excellence (NICE) Haematological Cancer: Improving Outcomes Guidance was published in 2003 and updated in 2016 (NG47), providing recommendations for service delivery including Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDSs). This survey assessed the implementation of NG47 guidelines, with a specific focus on implementation in relation to laboratory SIHMDS delivery., Methods: A survey was issued to the 17 SIHMDSs identified in England. The questionnaire covered laboratory configuration, information systems, integrated reporting and multidisciplinary team (MDT) working recommendations., Results: In the 10 responding SIHMDS, full implementation of recommendations was not achieved. Higher levels of implementation were reported in 'colocated' services compared with 'networked' SIHMDS. Increased guideline implementation was reported with longer duration since initial establishment of a SIHMDS and for laboratory based as opposed to clinical (MDT) reporting recommendations., Conclusions: Our survey highlights variable implementation of NICE guidance across SIHMDS, with likely inequity of access, standardisation and quality in haemato-oncology diagnostics. Provision of a more structured framework for guideline implementation could assist in increasing compliance to meet the goals of quality and equity of access to harmonised haemato-oncology diagnostics across the NHS in England. This would provide a basis for evaluating the clinical benefits and health economic impact of the SIHMDS model on patient care and outcomes., Competing Interests: Competing interests: JAS served as Clinical Lead for the 2016 Update of NICE Haematological Cancers: Improving Outcomes Guideline Committee (NG47)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
41. Automating outcome analysis after stem cell transplantation: The YORT tool.
- Author
-
von Asmuth EGJ, Putter H, Mohseny AB, Schilham MW, Snowden JA, Saccardi R, and Lankester AC
- Subjects
- Humans, Child, Recurrence, Transplantation Conditioning methods, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods
- Abstract
Hematopoietic stem cell transplantation is a high-risk procedure. Auditing and yearly outcome reviews help keep optimal quality of care and come with increased survival, but also has significant recurring costs. When data has been entered in a standardized registry, outcome analyses can be automated, which reduces work and increases standardization of performed analyses. To achieve this, we created the Yearly Outcome Review Tool (YORT), an offline, graphical tool that gets data from a single center EBMT registry export, allows the user to define filters and groups, and performs standardized analyses for overall survival, event-free survival, engraftment, relapse rate and non-relapse mortality, complications including acute and chronic Graft vs Host Disease (GvHD), and data completeness. YORT allows users to export data as analyzed to allow you to check data and perform manual analyses. We show the use of this tool on a two-year single-center pediatric cohort, demonstrating how the results for both overall and event-free survival and engraftment can be visualized. The current work demonstrates that using registry data, standardized tools can be made to analyze this data, which allows users to perform outcome reviews for local and accreditation purposes graphically with minimal effort, and help perform detailed standardized analyses. The tool is extensible to be able to accommodate future changes in outcome review and center-specific extensions., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
42. Correction: An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
- Author
-
Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
- Published
- 2023
- Full Text
- View/download PDF
43. An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
- Author
-
Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
- Subjects
- Humans, Cohort Studies, Neoplasm Recurrence, Local, Transplantation Conditioning, Melphalan, Transplantation, Autologous, Multiple Myeloma therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m
2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
- Full Text
- View/download PDF
44. Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.
- Author
-
Styczynski J, Tridello G, Koster L, Knelange N, Wendel L, van Biezen A, van der Werf S, Mikulska M, Gil L, Cordonnier C, Ljungman P, Averbuch D, Cesaro S, Baldomero H, Chabannon C, Corbacioglu S, Dolstra H, Glass B, Greco R, Kröger N, de Latour RP, Mohty M, Neven B, Peric Z, Snowden JA, Sureda A, Yakoub-Agha I, and de la Camara R
- Subjects
- Humans, Cause of Death, Chronic Disease, Retrospective Studies, Hematopoietic Stem Cell Transplantation methods, Communicable Diseases etiology, Lymphoma, Leukemia, Myeloid, Acute etiology
- Abstract
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
45. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.
- Author
-
Barnes E, Goodyear CS, Willicombe M, Gaskell C, Siebert S, I de Silva T, Murray SM, Rea D, Snowden JA, Carroll M, Pirrie S, Bowden SJ, Dunachie SJ, Richter A, Lim Z, Satsangi J, Cook G, Pope A, Hughes A, Harrison M, Lim SH, Miller P, Klenerman P, Basu N, Gilmour A, Irwin S, Meacham G, Marjot T, Dimitriadis S, Kelleher P, Prendecki M, Clarke C, Mortimer P, McIntyre S, Selby R, Meardon N, Nguyen D, Tipton T, Longet S, Laidlaw S, Orchard K, Ireland G, Thomas D, Kearns P, Kirkham A, and McInnes IB
- Subjects
- Humans, COVID-19 Vaccines, BNT162 Vaccine, ChAdOx1 nCoV-19, Vaccination, Antibodies, Viral, SARS-CoV-2, COVID-19
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml
-1 ). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
46. Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis.
- Author
-
Kalincik T, Sharmin S, Roos I, Freedman MS, Atkins H, Burman J, Massey J, Sutton I, Withers B, Macdonell R, Grigg A, Torkildsen Ø, Bo L, Lehmann AK, Havrdova EK, Krasulova E, Trnený M, Kozak T, van der Walt A, Butzkueven H, McCombe P, Skibina O, Lechner-Scott J, Willekens B, Cartechini E, Ozakbas S, Alroughani R, Kuhle J, Patti F, Duquette P, Lugaresi A, Khoury SJ, Slee M, Turkoglu R, Hodgkinson S, John N, Maimone D, Sa MJ, van Pesch V, Gerlach O, Laureys G, Van Hijfte L, Karabudak R, Spitaleri D, Csepany T, Gouider R, Castillo-Triviño T, Taylor B, Sharrack B, Snowden JA, Mrabet S, Garber J, Sanchez-Menoyo JL, Aguera-Morales E, Blanco Y, Al-Asmi A, Weinstock-Guttman B, Fragoso Y, de Gans K, and Kermode A
- Subjects
- Female, Humans, Adult, Natalizumab therapeutic use, Fingolimod Hydrochloride therapeutic use, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS)., Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials., Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics., Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab., Main Outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement., Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%)., Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.
- Published
- 2023
- Full Text
- View/download PDF
47. Practice harmonization workshops of EBMT: an expert-based approach to generate practical and contemporary guidelines within the arena of hematopoietic cell transplantation and cellular therapy.
- Author
-
Yakoub-Agha I, Greco R, Onida F, de la Cámara R, Ciceri F, Corbacioglu S, Dolstra H, Glass B, Kenyon M, McLornan DP, Neven B, de Latour RP, Peric Z, Ruggeri A, Snowden JA, Sureda A, and Sánchez-Ortega I
- Subjects
- Humans, Systematic Reviews as Topic, Consensus, Hematopoietic Stem Cell Transplantation
- Abstract
For hematopoietic cell transplantation (HCT) and cellular therapy (CT), clinical patient care is localized, and practices may differ between countries and from center to center even within the same country. Historically, international guidelines were not always adapted to the changing daily clinical practice and practical topics there were not always addressed. In the absence of well-established guidelines, centers tended to develop local procedures/policies, frequently with limited communication with other centers. To try to harmonize localized clinical practices for malignant and non-malignant hematological disorders within EBMT scope, the practice harmonization and guidelines (PH&G) committee of the EBMT will co-ordinate workshops with topic-specific experts from interested centers. Each workshop will discuss a specific issue and write guidelines/recommendations that practically addresses the topic under review. To provide clear, practical and user-friendly guidelines when international consensus is lacking, the EBMT PH&G committee plans to develop European guidelines by HCT and CT physicians for peers' use. Here, we define how workshops will be conducted and guidelines/recommendations produced, approved and published. Ultimately, there is an aspiration for some topics, where there is sufficient evidence base to be considered for systematic reviews, which are a more robust and future-proofed basis for guidelines/recommendations than consensus opinion., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
48. Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey.
- Author
-
Passweg JR, Baldomero H, Ciceri F, Corbacioglu S, de la Cámara R, Dolstra H, Glass B, Greco R, McLornan DP, Neven B, de Latour RP, Perić Z, Ruggeri A, Snowden JA, and Sureda A
- Subjects
- Humans, Child, SARS-CoV-2, Pandemics, Europe epidemiology, Receptors, Chimeric Antigen, COVID-19 therapy, Hematopoietic Stem Cell Transplantation, Neoplasms therapy
- Abstract
In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.4%, autologous HCT +3.9%, more pronounced in non-malignant disorders. Main indications for allogeneic HCT were myeloid malignancies 10,745 (58%), lymphoid malignancies 5127 (28%) and non-malignant disorders 2501 (13%). Main indications for autologous HCT were lymphoid malignancies 22,129 (90%) and solid tumors 1635 (7%). In allogeneic HCT, use of haploidentical donors decreased by -0.9% while use of unrelated and sibling donors increased by +4.3% and +9%. Cord blood HCT decreased by -5.8%. Pediatric HCT increased overall by +5.6% (+6.9% allogeneic and +1.6% autologous). Increase in the use of CAR-T was mainly restricted to high-income countries. The drop in HCT activity reported in 2020 partially recovered in 2021, the second year of the SARS-CoV-2 pandemic. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual EBMT report reflects current activities useful for health care resource planning., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
49. Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE).
- Author
-
Saccardi R, Putter H, Eikema DJ, Busto MP, McGrath E, Middelkoop B, Adams G, Atlija M, Ayuk FA, Baldomero H, Beguin Y, de la Cámara R, Cedillo Á, Balari AMS, Chabannon C, Corbacioglu S, Dolstra H, Duarte RF, Dulery R, Greco R, Gusi A, Hamad N, Kenyon M, Kröger N, Labopin M, Lee J, Ljungman P, Manson L, Mensil F, Milpied N, Mohty M, Oldani E, Orchard K, Passweg J, Pearce R, de Latour RP, Poirel HA, Rintala T, Rizzo JD, Ruggeri A, Sanchez-Martinez C, Sanchez-Guijo F, Sánchez-Ortega I, Trnková M, Ferreiras DV, Wilcox L, de Wreede LC, and Snowden JA
- Subjects
- Humans, Bone Marrow, Reproducibility of Results, Europe, Accreditation, Benchmarking, Hematopoietic Stem Cell Transplantation
- Abstract
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., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
50. Autoimmune manifestations in VEXAS: Opportunities for integration and pitfalls to interpretation.
- Author
-
Bruno A, Gurnari C, Alexander T, Snowden JA, and Greco R
- Subjects
- Male, Humans, Algorithms, Hematopoietic Stem Cells, Mutation, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation
- Abstract
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a novel entity manifesting with a multiplicity of clinical features. Somatic mutations of the UBA1 gene in hematopoietic stem cells constitute the genetic basis of VEXAS. As an X-linked disorder, most cases occur in men, classically developing symptoms during the fifth to sixth decade of life. Considering its multidisciplinary nature involving numerous branches of internal medicine, VEXAS has elicited a wide medical interest and several medical conditions have been associated with this disease. Even so, its recognition in everyday clinical practice is not necessarily straightforward. Close collaboration between different medical specialists is mandatory. Patients with VEXAS may manifest a range of features from manageable cytopenias to disabling and life-threatening autoimmune phenomena with limited responses to therapy, with the potential for progression to hematological malignancies. Diagnostic and treatment guidelines are exploratory and include a range of rheumatological and supportive care treatments. Allogeneic hematopoietic stem cell transplantation is potentially curative, but its risks are significant and its position in the treatment algorithm is yet to be defined. Herein, we present the variegated manifestations of VEXAS, provide practice criteria for diagnostic testing of UBA1, and discuss potential treatment options, including allogeneic hematopoietic stem cell transplantation, current evidence, and future directions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.