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Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize its safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Yet, structured recommendations are not commonly available. Here, the Transplant Center and Recipient Issues Standing Committee for the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements to establish a transplant program. First, we solicited components from committee members and grouped them in domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services and quality). Subsequently, reviewers scored all elements on a 7-point scale, from an absolute requirement (score of 1) to not required (score of 7). An independent group of five experienced transplant physicians reviewed the rankings. Minimum requirements to establish 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 >2.0-4.0 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 transplant program and to set the path for expansion and further development., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

An increasing cohort of haematopoietic cell transplantation (HCT) survivors has raised awareness of long-term and late effects. Updated recommendations for HCT late effects screening were published in 2012 [Majhail et al. Biology of Blood and Marrow Transplantation, 18 (2012):348]. We aimed to assess the clinical efficacy of a dedicated screening clinic to identify problems in HCT survivors using the international guidelines. Clinic letters and test results of the first 59 consecutive patients attending the screening clinic were evaluated. 30 females and 29 males (mean age of 49 years, range 22-74) were included. The mean time since transplant was 6 years (0.5-18). 49/65 transplants were allogeneic. Primary indications for HCT were myeloid (56%), lymphoid (37%), solid tumour (5%) and auto-immune diseases (2%). 134 complications were reported (mean 2, range 0-8), with 114 documented further actions/referrals. The most commonly reported concerns were pain 18/59 (31%), fatigue 14/59 (24%), sexual function 14/59 (24%) and sleep disturbance 11/59 (19%). Second primary malignancies were recorded in five cases. Implementation and audit of the international late effect screening guidelines confirm the need for systematic long-term physical and psychological screening and care, thus ensuring timely and efficient identification of problems and the opportunity to minimise morbidity effects and optimise health., (© 2016 John Wiley & Sons Ltd.)

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process.

Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT.

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.

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.

Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

We report a patient who underwent allogeneic bone marrow transplantation from a sibling with longstanding untreated severe active rheumatoid arthritis. After 4 years of follow-up there is no evidence of adoptive transfer of rheumatoid arthritis to the recipient. This case, along with another recently reported case, provides reassurance that haemopoietic stem cell transplantation from a donor with systemic autoimmune disease may not necessarily result in adoptive transfer of the disease. All previous reports of transfer of autoimmunity in humans have been of organ-specific autoimmune diseases and we speculate that pathophysiological differences might account for why systemic autoimmune disease is not transferred.

Transfer of donor immunity has been demonstrated in animal models of both allogeneic and syngeneic bone marrow transplantation (BMT). Clinical case reports have suggested that human autoimmune disease may be similarly transferred. However, it is difficult to completely exclude autoimmune phenomena associated with graft-versus-host disease (GVHD) as previously reported cases are of allogeneic BMT. In addition, the onset of autoimmunity has been distantly related to the timing of the transplant, perhaps because of the immunosuppression used for prophylaxis and treatment of GVHD. We describe a patient in whom the development of psoriasis shortly after receiving syngeneic bone marrow from a psoriatic donor and its recurrence with arthropathy following a second syngeneic BMT provide more direct evidence for the adoptive transfer of human autoimmune disease, probably by T cells.

We describe a patient with longstanding steroid-dependent systemic lupus erythematosus (SLE) in whom clinical and serological remission was achieved following high-dose therapy and autologous bone marrow rescue for high-grade non-Hodgkin's lymphoma. However, 3 years later, autoimmune disease re-presented in the form of immune thrombocytopenia (ITP), which had not previously been a feature of the SLE, necessitating reintroduction of steroid immunosuppression. Relapse of SLE is most likely, although de novo ITP post-BMT is also a possibility. The case suggests that severe long-standing autoimmune disease may be controlled by high-dose therapy and autologous stem cell reconstitution. However, further studies are required to determine the mechanism of re-emergence of autoimmunity and to evaluate optimal regimens and the potential value of such therapy in severe autoimmune diseases.