17 results on '"Snowden, JA"'
Search Results
2. Gender gaps in transplantation.
- Author
-
Gratwohl A, Snowden JA, and Brand R
- Subjects
- Female, Humans, Male, Gender Identity, Hematopoietic Stem Cell Transplantation methods, Organ Transplantation methods, Transplantation Conditioning methods
- Published
- 2020
- Full Text
- View/download PDF
3. Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Cell Transplantation Program, Part I: Minimum Requirements and Beyond.
- Author
-
Pasquini MC, Srivastava A, Ahmed SO, Aljurf M, Atsuta Y, Doleysh C, Galeano S, Gluckman E, Greinix H, Hale GA, Hari P, Hashmi SK, Kamani N, Laughlin MJ, Niederwieser D, Seber A, Szer J, Snowden JA, Van Biesen K, Watry P, Weisdorf DJ, and Apperley J
- Subjects
- Humans, Practice Guidelines as Topic, Transplantation, Autologous, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Societies, Medical, Transplantation Conditioning
- Abstract
Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Structured recommendations are not commonly available, however. The Transplant Center and Recipient Issues Standing Committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements for establishing a transplantation program. First, we solicited components from committee members and grouped them into domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services, and quality). Subsequently, reviewers scored each element on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). An independent group of 5 experienced transplantation physicians reviewed the rankings. The minimum requirements for establishing any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores of >2.0 to 4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤ 7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplantation program and set the stage for expansion and further development., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
4. The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies.
- Author
-
Passweg JR, Baldomero H, Basak GW, Chabannon C, Corbacioglu S, Duarte R, Kuball J, Lankester A, Montoto S, de Latour RP, Snowden JA, Styczynski J, Yakoub-Agha I, Arat M, Mohty M, and Kröger N
- Subjects
- Female, History, 21st Century, Humans, Male, Surveys and Questionnaires, Hematopoietic Stem Cell Transplantation methods, Neoplasms therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
- Published
- 2019
- Full Text
- View/download PDF
5. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019.
- Author
-
Duarte RF, Labopin M, Bader P, Basak GW, Bonini C, Chabannon C, Corbacioglu S, Dreger P, Dufour C, Gennery AR, Kuball J, Lankester AC, Lanza F, Montoto S, Nagler A, Peffault de Latour R, Snowden JA, Styczynski J, Yakoub-Agha I, Kröger N, and Mohty M
- Subjects
- Europe, History, 21st Century, Humans, Hematologic Diseases therapy, Hematopoietic Stem Cell Transplantation methods, Immune System Diseases therapy, Neoplasms therapy, Transplantation Conditioning methods
- Abstract
This is the seventh special EBMT report on the indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on transplant indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. In over two decades since the first report, the EBMT indications manuscripts have incorporated changes in transplant practice coming from scientific and technical developments in the field. In this same period, the establishment of JACIE accreditation has promoted high quality and led to improved outcomes of patient and donor care and laboratory performance in transplantation and cellular therapy. An updated report with operating definitions, revised indications and an additional set of data with overall survival at 1 year and non-relapse mortality at day 100 after transplant in the commonest standard-of-care indications is presented. Additional efforts are currently underway to enable EBMT member centres to benchmark their risk-adapted outcomes as part of the Registry upgrade Project 2020 against national and/or international outcome data.
- Published
- 2019
- Full Text
- View/download PDF
6. Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation.
- Author
-
Ros-Soto J, Snowden JA, Salooja N, Gilleece M, Parker A, Greenfield DM, Anthias C, Alfred A, Harrington A, Peczynski C, Peggs K, Madrigal A, Basak GW, and Schoemans H
- Subjects
- Europe, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, Surveys and Questionnaires, Transplantation, Homologous methods, Vitamin D pharmacology, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Vitamin D therapeutic use, Vitamin D Deficiency therapy
- Abstract
Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
7. Allogeneic HSCT for Autoimmune Diseases: A Retrospective Study From the EBMT ADWP, IEWP, and PDWP Working Parties.
- Author
-
Greco R, Labopin M, Badoglio M, Veys P, Furtado Silva JM, Abinun M, Gualandi F, Bornhauser M, Ciceri F, Saccardi R, Lankester A, Alexander T, Gennery AR, Bader P, Farge D, and Snowden JA
- Subjects
- Acute Disease, Adolescent, Adult, Age Factors, Allografts, Child, Child, Preschool, Female, Humans, Incidence, Infant, Male, Middle Aged, Retrospective Studies, Sex Factors, Autoimmune Diseases epidemiology, Autoimmune Diseases immunology, Autoimmune Diseases therapy, Graft vs Host Disease epidemiology, Graft vs Host Disease immunology, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning
- Abstract
Background: This retrospective study assessed the use and long-term outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe autoimmune diseases (ADs), reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Methods: Between 1997 and 2014, 128 patients received allogeneic HSCT for various hematological ( n = 49) and non-hematological ( n = 79) refractory ADs. The median age was 12.7 years (0.2-62.2). Donors were syngeneic for seven, matched related for 46, unrelated for 51, haploidentical for 15, and cord blood for nine patients. Results: The incidence of grades II-IV acute graft-vs.-host disease (GvHD) was 20.8% at 100 days. Cumulative incidence of chronic GvHD was 27.8% at 5-years. Non-relapse mortality (NRM) was 12.7% at 100-days. Overall survival (OS) and Progression-Free Survival (PFS) were 70.2 and 59.4% at 5-years, respectively. By multivariate analysis, age <18 years, males, and more recent year of transplant were found to be significantly associated with improved PFS. Reduced conditioning intensity was associated with a lower NRM. On a subgroup of 64 patients with detailed information a complete clinical response was obtained in 67% of patients at 1-year. Conclusions: This large EBMT survey suggests the potential of allogeneic HSCT to induce long-term disease control in a large proportion of refractory ADs, with acceptable toxicities and NRM, especially in younger patients.
- Published
- 2019
- Full Text
- View/download PDF
8. Vitamin D: is it important in haematopoietic stem cell transplantation? A review.
- Author
-
Ros-Soto J, Anthias C, Madrigal A, and Snowden JA
- Subjects
- Hematopoietic Stem Cell Transplantation methods, Humans, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects, Vitamin D metabolism, Vitamin D Deficiency complications
- Abstract
Vitamin D has effects on several body systems, from well-established role in bone metabolism to emerging effects on the immune system. Increasing evidence supports an immunomodulatory effect including inhibition of the pro-inflammatory lymphocyte subsets while enhancing their anti-inflammatory counterpart, in favour of a more tolerogenic status. Vitamin D deficiency is increasingly recognised in association with autoimmune and inflammatory diseases, also with evidence from the field of asthma where vitamin D supplementation may overcome steroid resistance. In the HSCT setting, vitamin D deficiency has been variably associated with increased complications, including graft-versus-host disease (GvHD), with a potential impact on survival outcomes. In this review we provide an overview and critical appraisal of the current literature of the role of vitamin D (and its deficiency) in relation to immunity in both allogeneic and autologous HSCT settings. We conclude that the evidence base is mixed, but a greater understanding of the role of vitamin D in relation to immune reconstitution following HSCT is warranted. Given its potential benefits, its inexpensive cost and favourable side effect profile, consideration of vitamin D levels and its supplementation could be easily incorporated into prospective studies in GvHD, including clinical trials of novel therapeutics, supportive care and biomarkers.
- Published
- 2019
- Full Text
- View/download PDF
9. Recommendations from the European Society for Blood and Marrow Transplantation (EBMT) for a curriculum in hematopoietic cell transplantation.
- Author
-
Mohty M, Duarte RF, Kuball J, Bader P, Basak GW, Bonini C, Carreras E, Chabannon C, Dufour C, Gennery A, Lankester A, Lanza F, Ljungman P, Montoto S, Nagler A, Snowden JA, Styczynski J, Sureda A, and Kröger N
- Subjects
- Europe, Humans, Bone Marrow Transplantation methods, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Hematopoietic cell transplantation (HCT) is increasingly used worldwide. This treatment approach is complex and requires specific knowledge and training. The European Society for Blood and Marrow Transplantation (EBMT) identified the need for a set of international recommendations for the clinical training of physicians to qualify them as being competent in performing HCT procedures as well as novel cellular immune therapies and taking care of such patients. The goal is to implement an EBMT HCT-focused global curriculum (EBMT-GC) that can serve as a tool for the development of the HCT sub-specialty worldwide. Despite the diversity and heterogeneity of health and educational systems around the globe, this set of recommendations can be fairly adopted by any national educational and health authorities and can be adjusted to specific conditions and resources of a given country, if needed. The ultimate goal of the EBMT-GC is to define standards for personal knowledge in allogeneic stem cell transplantation for physicians worldwide in order to ensure that all patients will receive treatment by well-trained physicians.
- Published
- 2018
- Full Text
- View/download PDF
10. The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial.
- Author
-
Striha A, Ashcroft AJ, Hockaday A, Cairns DA, Boardman K, Jacques G, Williams C, Snowden JA, Garg M, Cavenagh J, Yong K, Drayson MT, Owen R, Cook M, and Cook G
- Subjects
- Antineoplastic Agents adverse effects, Boron Compounds adverse effects, Clinical Trials, Phase III as Topic, Drug Administration Schedule, Female, Glycine administration & dosage, Glycine adverse effects, Humans, Maintenance Chemotherapy adverse effects, Maintenance Chemotherapy mortality, Male, Multicenter Studies as Topic, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Neoplasm, Residual, Progression-Free Survival, Proteasome Inhibitors adverse effects, Quality of Life, Randomized Controlled Trials as Topic, Recurrence, Salvage Therapy, Stem Cell Transplantation adverse effects, Stem Cell Transplantation mortality, Time Factors, Transplantation Conditioning adverse effects, Transplantation Conditioning mortality, Transplantation, Autologous, Treatment Outcome, United Kingdom, Antineoplastic Agents administration & dosage, Boron Compounds administration & dosage, Glycine analogs & derivatives, Maintenance Chemotherapy methods, Multiple Myeloma therapy, Proteasome Inhibitors administration & dosage, Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance., Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCT
Con , using high-dose melphalan, or ASCTAug , using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression., Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM., Trial Registration: ISRCTN, ISRCTN10038996 . Registered on 15 December 2016.- Published
- 2018
- Full Text
- View/download PDF
11. Conditioning regimens for autologous haematopoietic stem cell transplantation - can natural killer cell therapy help?
- Author
-
Snowden JA and Hill GR
- Subjects
- Humans, Immunotherapy, Adoptive, Killer Cells, Natural, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning
- Published
- 2017
- Full Text
- View/download PDF
12. Lineage-specific chimerism monitoring after allogeneic haematopoietic stem cell transplantation: do we really know what we are measuring?
- Author
-
Watson MB, Clouston HJ, Snowden JA, Wilson G, Durkie M, Ward R, Kaur H, Travis D, and Barnett D
- Subjects
- Chimerism, Female, Humans, Male, Transplantation Conditioning mortality, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Transplantation, Homologous methods
- Published
- 2017
- Full Text
- View/download PDF
13. Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols.
- Author
-
Hough R, Danby R, Russell N, Marks D, Veys P, Shaw B, Wynn R, Vora A, Mackinnon S, Peggs KS, Crawley C, Craddock C, Pagliuca A, Cook G, Snowden JA, Clark A, Marsh J, Querol S, Parkes G, Braund H, and Rocha V
- Subjects
- Algorithms, Clinical Protocols, Cord Blood Stem Cell Transplantation methods, Histocompatibility Testing methods, Humans, United Kingdom, Cord Blood Stem Cell Transplantation standards, Donor Selection, Transplantation Conditioning methods
- Abstract
Allogeneic haemopoietic stem cell transplantation offers a potentially curative treatment option for a wide range of life-threatening malignant and non-malignant disorders of the bone marrow and immune system in patients of all ages. With rapidly emerging advances in the use of alternative donors, such as mismatched unrelated, cord blood and haploidentical donors, it is now possible to find a potential donor for almost all patients in whom an allograft is indicated. Therefore, for any specific patient, the transplant physician may be faced with a myriad of potential choices, including decisions concerning which donor to prioritize where there is more than one, the optimal selection of specific umbilical cord blood units and which conditioning and graft-versus-host disease prophylactic schedule to use. Donor choice may be further complicated by other important factors, such as urgency of transplant, the presence of alloantibodies, the disease status (homozygosity or heterozygosity) of sibling donors affected by inherited disorders and the cytomegalovirus serostatus of patient and donor. We report UK consensus guidelines on the selection of umbilical cord blood units, the hierarchy of donor selection and the preferred conditioning regimens for umbilical cord blood transplantation, with a summary of rationale supporting these recommendations., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
14. Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation.
- Author
-
Marsh JC, Pearce RM, Koh MB, Lim Z, Pagliuca A, Mufti GJ, Perry J, Snowden JA, Vora AJ, Wynn RT, Russell N, Gibson B, Gilleece M, Milligan D, Veys P, Samarasinghe S, McMullin M, Kirkland K, and Cook G
- Subjects
- Adolescent, Adult, Aged, Alemtuzumab, Bone Marrow Cells cytology, Child, Child, Preschool, Female, Graft Survival, Graft vs Host Disease, Humans, Infant, Male, Middle Aged, Registries, Retrospective Studies, Risk Factors, Siblings, Tissue Donors, Treatment Outcome, United Kingdom, Young Adult, Anemia, Aplastic therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antilymphocyte Serum therapeutic use, Bone Marrow Transplantation methods, Peripheral Blood Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.
- Published
- 2014
- Full Text
- View/download PDF
15. Improving safety in autologous HSCT for systemic sclerosis.
- Author
-
Snowden JA, Akil M, and Kiely DG
- Subjects
- Female, Humans, Male, Cause of Death, Heart Failure mortality, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation mortality, Pericarditis, Constrictive mortality, Peripheral Blood Stem Cell Transplantation methods, Peripheral Blood Stem Cell Transplantation mortality, Scleroderma, Diffuse mortality, Scleroderma, Diffuse therapy, Scleroderma, Limited mortality, Scleroderma, Limited therapy, Sepsis mortality, Transplantation Conditioning
- Published
- 2013
- Full Text
- View/download PDF
16. Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.
- Author
-
Chantry AD, Snowden JA, Craddock C, Peggs K, Roddie C, Craig JI, Orchard K, Towlson KE, Pearce RM, and Marks DI
- Subjects
- Acute Disease, Adolescent, Adult, Age Factors, Aged, Busulfan administration & dosage, Busulfan adverse effects, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Etoposide administration & dosage, Etoposide adverse effects, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Registries statistics & numerical data, Remission Induction, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation Conditioning methods, United Kingdom epidemiology, Whole-Body Irradiation statistics & numerical data, Bone Marrow Transplantation statistics & numerical data, Leukemia, Myeloid surgery, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Salvage Therapy, Transplantation Conditioning statistics & numerical data, Transplantation, Autologous statistics & numerical data
- Abstract
Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.
- Published
- 2006
- Full Text
- View/download PDF
17. The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial
- Author
-
Striha, A, Ashcroft, AJ, Hockaday, A, Cairns, DA, Boardman, K, Jacques, G, Williams, C, Snowden, JA, Garg, M, Cavenagh, J, Yong, K, Drayson, MT, Owen, R, Cook, M, and Cook, G
- Subjects
Boron Compounds ,Male ,Neoplasm, Residual ,Time Factors ,Transplantation Conditioning ,Glycine ,Antineoplastic Agents ,Transplantation, Autologous ,Drug Administration Schedule ,Randomised ,Maintenance Chemotherapy ,Study Protocol ,Recurrence ,Multiple myeloma ,Journal Article ,Humans ,Multicenter Studies as Topic ,ASCT ,Randomized Controlled Trials as Topic ,Augmented ASCT ,Salvage Therapy ,lcsh:R5-920 ,Progression-Free Survival ,United Kingdom ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Quality of Life ,Female ,lcsh:Medicine (General) ,Proteasome Inhibitors ,Depth of response ,Haematology ,Stem Cell Transplantation - Abstract
Background Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM. Trial registration ISRCTN, ISRCTN10038996. Registered on 15 December 2016. Electronic supplementary material The online version of this article (10.1186/s13063-018-2524-8) contains supplementary material, which is available to authorized users.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.