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The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (

Background: Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. Design: The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field. Results: Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post- authorisation safety surveillance and regulatory issues. Conclusions: We provide practical, clinically relevant recommendations on the use of these high- cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic. Keywords: B-cell acute lymphoblastic leukemia (B ALL) ; CAR T-cells ; cytokine release syndrome (CRS) ; immune effector cell associated neurotoxicity syndrome (ICANS) ; large B-cell lymphoma (LBCL) ; multiple myeloma (MM).

PURPOSE: Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. \ud \ud \ud \ud METHODS: Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). \ud \ud \ud \ud RESULTS: A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment ( P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment ( P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. \ud \ud \ud \ud CONCLUSION: Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

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. ispartof: Biology Of Blood And Marrow Transplantation vol:25 issue:10 pages:2079-2085 ispartof: location:United States status: published

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.

Objectives:\ud To investigate the characteristics, methodology, quality, and efficacy of psychological interventions for distress in adult patients undergoing haematopoietic stem cell\ud transplantation (HSCT).\ud \ud Methods:\ud A systematic review of relevant studies was conducted using six databases with supplementary hand searching. Included studies employed an experimental or quasiexperimental\ud design, interventions included at least one psychological component, and outcomes involved psychological distress in affective terms. Data were abstracted and study\ud quality was assessed using Cochrane Foundation criteria amended to include confounder and common factors control. Data were examined and synthesised using a narrative approach and meta-analysis.\ud \ud Results:\ud Eleven articles for nine interventions met the inclusion criteria out of 11741 abstracts. The studies varied in quality, general, intervention, and methodological characteristics while findings were mixed. Interventions tended to show better efficacy when incorporating a\ud major psychological component involving cognitive behavioural or emotional processing methods with substantial interventionist input. However, this was also associated with methodological limitations and threats to internal validity such as poor confounder and common factors control. A meta-analysis yielded a small but significant pooled effect size estimate in favour of interventions with inconsequential heterogeneity. Risk of bias remained a concern. \ud \ud Conclusions:\ud Psychological interventions may provide some benefit in alleviating distress in HSCT but conclusions remain tentative in light of methodological limitations and risk of bias. Further research is needed to evidence the individual contribution of intervention components and mechanism of change together with improving intervention efficiency and\ud methodological quality.

We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow harvests and 174 peripheral blood stem cell mobilizations were performed on 187 patients. Disease indications were multiple sclerosis (76 patients), rheumatoid arthritis (37 patients), scleroderma (26 patients), systemic lupus erythematosus (19 patients), juvenile chronic arthritis (13 patients), idiopathic autoimmune thrombocytopenia (8 patients), Behcet's disease (3 patients), undifferentiated vasculitis (3 patients), polychondritis (1 patient) and polymyositis (1 patient). Bone marrow harvests were used in the Peoples Republic of China and preferred worldwide for children. PBSC mobilization was the preferred technique for adult stem cell collection in America, Australia, and Europe. Methods of PBSC mobilization included G-CSF (5, 10, or 16 mug/kg/day) or cyclophosphamide (2 or 4 g/m(2)) with either G-CSF (5 or 10 mug/kg/day) or GM-CSF (5 mug/kg/day). Bone marrow harvests were without complications and did not affect disease activity. A combination of cyclophosphamide and G-CSF was more likely to ameliorate disease activity than G-CSF alone (P

Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis.The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire.Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer.Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.

Over the past 15 years, SCT has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies recently provided the proof-of-concept that restoration of immunological tolerance can be achieved by haematopoietic SCT in chronic autoimmunity through eradication of the pathologic, immunologic memory and profound reconfiguration of the immune system, that is, immune ‘resetting’. Nevertheless, a number of areas remain unresolved and warrant further investigation to refine our understanding of the underlying mechanisms of action and to optimize clinical SCT protocols. Due to the low number of patients transplanted in each centre, it is essential to adequately collect and analyse biological samples in a larger cohort of patients under standardized conditions. The European society for blood and marrow transplantation Autoimmune Diseases and Immunobiology Working Parties have, therefore, undertaken a joint initiative to develop and implement guidelines for ‘good laboratory practice’ in relation to procurement, processing, storage and analysis of biological specimens for immune reconstitution studies in AD patients before, during and after SCT. The aim of this document is to provide practical recommendations for biobanking of samples and laboratory immune monitoring in patients with ADs undergoing SCT, both for routine supportive care purposes and investigational studies.