Bone Marrow Transplantation (2019) 54:933–942 https://doi.org/10.1038/s41409-019-0430-7 PERSPECTIVE General information for patients and carers considering haematopoietic stem cell transplantation (HSCT) for severe autoimmune diseases (ADs): A position statement from the EBMT Autoimmune Diseases Working Party (ADWP), the EBMT Nurses Group, the EBMT Patient, Family and Donor Committee and the Joint Accreditation Committee of ISCT and EBMT (JACIE) Helen Jessop1 Dominique Farge 2,3,4,5 Riccardo Saccardi6 Tobias Alexander7 Montserrat Rovira8 ● ● ● ● ● Basil Sharrack9 Raffaella Greco10 Nico Wulffraat11 John Moore12 Majid Kazmi13 Manuela Badoglio ● ● ● ● ● 14 ● Gillian Adams15 Bregje Verhoeven15 John Murray16 John A. Snowden 1 ● ● ● Received: 10 October 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published online: 31 January 2019 © The Author(s) 2019. This article is published with open access 1234567890();,: 1234567890();,: Abstract Over the last 20 years, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with severe autoimmune and inflammatory diseases whose response to standard treatment options has been limited, resulting in a poor long-term prognosis in terms of survival or disability. The vast majority of patients have received autologous HSCT where an increasing evidence-base supports its use in a wide range of autoimmune diseases, particularly relapsing remitting MS, systemic sclerosis and Crohn’s disease. Compared with standard treatments for autoimmune diseases, HSCT is associated with greater short-term risks, including a risk of treatment-related mortality and long-term complications. There is a need for a careful appraisal of potential benefits and risks by disease and transplant specialists working closely together with patients and carers to determine individual suitability for HSCT. HSCT should be conducted in accredited transplant centres with robust arrangements for long-term follow-up with both disease and transplant specialists. The aim of this open-access position statement is to provide plainly worded guidance for patients and non-specialist clinicians considering HSCT for an autoimmune disease, especially when treatment abroad is being considered. Recent technical publications in the field have been referenced to support the statement and provide more detail for clinicians advising patients. Introduction connective tissue diseases affect many organs, typically causing inflammation and scarring of the skin, heart, Autoimmune diseases (ADs) are a broad group of illnesses lungs, kidneys and other organs. Multiple sclerosis (MS) where the body’s immune system reacts against its own affects the brain and spinal cord, whereas Crohn’s disease tissues and organs. The immune attack is followed by affects the gut. chronic inflammation and abnormal healing, which may be Treatment with immunosuppressant drugs, including associated with permanent organ damage, disability and disease modifying treatments (DMTs), may be successful in poor quality of life. In some cases, severe ADs may shorten controlling the AD, but there is an increased susceptibility life expectancy or even be immediately life-threatening. to infection and organ damage, which add to the problems The types of organs affected vary between ADs. For of living with an AD. example, systemic sclerosis, lupus, vasculitis and other Some patients have very aggressive forms of auto- immune disease which are poorly controlled by standard therapies. In some of these severely affected patients, there * John A. Snowden may be benefit in considering bone marrow transplantation john.snowden@sth.nhs.uk (BMT), or, as it is now more commonly known, haemato- Extended author information available on the last page of the article poietic stem cell transplantation (HSCT) [1–3]. 934 H. Jessop et al. HSCT: general background 2. Stem cells collected from peripheral blood HSCT is commonly used for the treatment of serious blood diseases, including leukaemia, myeloma and lymphomas. 3. Stem cells frozen Many haematology departments will provide HSCT as a 1. Mobilise stem cells until required using growth factor and treatment for these common indications, having carefully chemotherapy weighed up the survival benefits and serious risks of HSCT against the non-transplant treatment options, such as che- 7. Further follow-up as outpatient for 2-3 months motherapy and modern biological agents [4, 5]. with regular blood tests 4. Conditioning chemotherapy to The process of HSCT involves giving high doses of and medication suppress immune system chemotherapy and/or radiotherapy and then infusing mobilized blood, cord blood or marrow-derived (i.e.,’ hae- 6. Support with blood 5. Stem cells thawed matopoietic’) stem cells from the patients themselves products and antibiotics and re-infused (approximately 2 weeks) (autologous or auto-transplant) or from donors (allogeneic Fig. 1 Summary of autologous HSCT procedure. In addition, robust or allo-transplant) to rebuild the bone marrow and the long-term follow-up arrangements should be individualised with each immune system, hopefully without the disease. patient with both disease and transplant specialists The HSCT process is summarised in Fig. 1. Recognised early complications include acute toxicities experienced during the procedure, such as infection, bleeding, anaemia and much more challenging to treat when established. and organ toxicities. Blood transfusions are usually needed Patients need to be monitored, and provided with a con- to support the patients during this phase of the treatment. sistent supply of prophylactic (preventative) antibiotics, Complications may be life-threatening and irreversible and which reduce hospitalisation for serious and sometimes therefore HSCT should only be performed after a full dis- life-threatening complications. Vaccination should be con- cussion of the risks and how they may be justified in terms sidered according to current guidelines for immunocom- of potential benefits from the treatment. Treatment-related promised patients [9]. mortality (TRM) risks depend on the type of transplant, the Long-term monitoring is essential. The so-called ‘late disease being treated and the individual patient. Even in effects’ of HSCT are common and may involve many patients treated in accredited transplant centres, TRM risk organ systems, including glandular (endocrine), bone, ranges from around 1% in good risk patients undergoing cardiovascular, respiratory and neurological. HSCT can autologous HSCT to considerably higher in patients with also result in an increased risk of ‘new’ cancers, and have more risk factors (e.g., severe organ damage or disability) an impact on patients’ psychological and emotional well- and with allogeneic HSCT, where TRM risk commonly being. Reproductive impairment can be frequent, and exceeds 10%. Responsible treating clinicians need to openly programmes for prevention of chemotherapy-associated discuss and individualise these risks for patients as part of sterility should therefore be proposed prior to HSCT. the informed consent process. Allogeneic HSCT may also be associated with risks of The risks of the HSCT procedure are not limited to the graft-versus-host disease, a potentially severe immune inpatient phase prior to recovery of blood counts [6–8]. complication that may affect several organs. There is even Following hospital discharge after the HSCT procedure, a risk of new ADs (known as ‘secondary’ autoimmune given the risk of ongoing complications, especially the risk diseases) after both autologous and allogeneic HSCT. In of sudden onset of serious and life-threatening complica- recognition of these ‘late effects’, the EBMT and other tions including infection, there should always be robust organisations have produced recommendations for long- plans for follow up and urgent management of complica- term follow-up of patients who should have life-long tions. Patients should be able to self-refer into a haematol- follow-up by clinicians familiar with ‘late effects’ fol- ogy or other department familiar with HSCT on a 7-day, lowing HSCT, irrespective of where the procedure has 24-h basis, and the transplant unit should organise regular been performed [6–9]. outpatient monitoring in the first 2 years following the Transplant centres should have approval of their ‘quality’ procedure and thereafter if needed. The risks of infection by external accreditation organisations (Joint Accreditation persist for long periods after HSCT, and ‘prophylactic’ Committee of ISCT & EBMT, JACIE, or its North Amer- (preventative) antibiotics are recommended for many ican equivalent, the Foundation for Cellular Therapy, months, or sometimes even life-long. Even though patients FACT), and there is published evidence supporting may feel well, some complications, including certain types improved safety and survival outcomes with accreditation of pneumonia, may be rapid in their onset and progression [10, 11]. General information for patients and carers considering haematopoietic stem cell transplantation (HSCT). . . 935 Haematopoietic stem cell transplantation In view of these toxicities and risks, it is very important that (HSCT) for ADs patients have a full discussion with their transplant and autoimmune disease specialist teams. Over the last 20 years, HSCT has also been used to treat The individual patient’s response to HSCT is dependent on severe ADs, as it is an effective means by which to suppress the specific AD and the stage of the disease at the time of the abnormal inflammation and associated scarring [1–3]. It treatment e.g., whether the inflammatory disease process can is also possible that HSCT can rebuild an altered immune be ‘switched off’ before it has become irreversible or has system that does not regenerate the original AD, or at least caused permanent organ damage. Some patients have had leads to a milder form and better disease control. To date, very profound responses lasting many years, far more than several thousand patients with ADs have been treated expected from treatment with standard therapies, but others worldwide with HSCT, with almost 3000 patients registered respond less well or experience a relapse of their AD soon in the EBMT registry (summarised in Table 1). after the transplant. The benefit of HSCT in some ADs (MS, The main ADs treated are currently relapsing remitting SSc and Crohn’s disease) has been shown in randomized MS, systemic sclerosis (SSc), systemic lupus erythematosus controlled trials (RCTs) against the best available conventional (SLE or ‘lupus’) and Crohn’s disease. Other rare immune therapy for an AD. However, there is always need for more disorders have been treated in smaller numbers. The vast evidence to help improve outcomes, and, when possible, AD majority of patients have been treated with autologous patients should be treated on ethically approved clinical HSCT, with MS, SSc and Crohn’s disease being the main studies. current indications, reflected by the registrations for the years following the publication of the EBMT ADWP guidelines and recommendations [12] in 2012 (Table 1). A Specific advice to patients considering HSCT small proportion of patients have received allogeneic for their AD HSCT, predominantly for rare diseases in the paedatric age group. We recommend that before starting treatment, patients It should be emphasized that HSCT is not a form of should inform themselves firstly about current disease and ‘regenerative’ stem cell therapy in the same way as many treatment guidelines, secondly about the professional com- scientists hope that stem cells may be used to rebuild new petence of the clinicians and thirdly the experience and organs. HSCT may lead to ‘re-setting‘ or ‘re-booting’ of the accreditation status of the transplant centre. immune system, which in turn may lead to improvement in The European Society of Blood & Marrow Transplan- damaged organs and tissues. HSCT works best if active tation (EBMT) has published a number of guidelines and inflammation can be switched off, but the effect of HSCT may recommendations for the use of HSCT in ADs [11–13]. be limited (or nothing at all) if there is no active inflammation. Other organisations and individual health professionals There is no proof that the blood stem cells can directly rebuild have also made recommendations in specific diseases specialised tissues, although in the absence of inflammation [14–17]. Whereas these guidelines are primarily intended some damaged tissues and organs may heal over time. The for a professional readership and therefore written in a potential mechanism by which autologous HSCT leads to a re- technical language, they are openly accessible to all. setting or re-balancing of the immune system in autoimmune Timing of HSCT is central to decision-making. The disease is summarised in Fig. 2. severity of the autoimmune disease, its treatment-resistance Although HSCT is common in many haematology and and availability of other treatment options are essential con- oncology departments, use of HSCT in ADs is relatively siderations. However, HSCT needs to be considered before rare and only a small number of transplant centres in each organ damage caused by the autoimmune disease becomes country have a good level of experience in working with irreversible (limiting benefits) and before the risks of HSCT disease specialists to select the most appropriate patients are significantly increased by compromised vital organ with AD and then deliver the HSCT treatment as safely as function. Balancing potential benefits and risks for individual possible. patients is often complex and requires disease specialists and The type of HSCT almost always used in patients with transplant clinicians to work closely together. severe ADs is autologous HSCT (or ‘auto-transplant’). The EBMT recommend that patients ask their transplant Auto-transplant is more safely delivered compared with and disease specialists to explain any aspect of the guide- allogeneic HSCT (or ‘allo-transplant’), which is a much lines, including whether treatment is in line with the pub- more complex procedure requiring a donor. Even so, there lished recommendations. are significant risks and toxicities with autologous HSCT, Treating clinicians should be active in the EBMT and/or which are an important consideration, especially if the AD other national and international professional societies, has already caused significant organ damage and disability. which means that they should follow published guidelines, 936 H. Jessop et al. Table 1 Summary of major Autologous HSCT for each category Total adult Total children (≤18 years Total patients treated categories and types of of autoimmune disease patients (1994– at the time of transplant, in the last 6 years (all autoimmune diseases treated 2018) 1994–2018) ages, 2012–2017) with HSCT in the EBMT registry, as per August 2018 All diseases 2387 162 1090 Neurological diseases Multiple sclerosis 1232 27 679 Other neurological diseases 94 3 51 Rheumatological diseases Systemic sclerosis 534 12 222 Systemic lupus erythematosus 89 18 9 (SLE or ‘lupus’) Other connective tissue diseases 46 5 8 Inflammatory arthritis (including 97 67 8 rheumatoid arthritis) Vasculitis (inflammation of the 39 4 10 blood vessels) Inflammatory bowel diseases Crohn’s and other 177 15 83 Haematological autoimmune diseases (causing low blood counts) Autoimmune cytopenia, haemolytic 41 8 8 anaemia, Evans syndrome, neutropenia and other Type 1 diabetes mellitus 20 0 3 Miscellaneous other autoimmune 18 3 9 diseases The table summarises activity in autologous HSCT, which accounts for the vast majority of procedures. Since 1996, 145 allogeneic transplants (from related and unrelated donors) have been performed for autoimmune diseases, approximately three quarters (73%) in children under the age of 18 for a range of haematological, rheumatological and other conditions Bold type denotes the sum total for each column Fig. 2 Mechanism of immune Cryopreservation re-setting with autologous Infections Genetic HSCT in autoimmune diseases tendency Other Dietary environmental Stem cell harvest Stem cell infusion triggers factors Self-reactive cells g rin chemotherapy + antibodies attacking normal to tissues o ni m nt Immune suppressive tie pa Autoimmune Patient ut Chemotherapy O Growth factor disease selection and workup Inpatient recovery Immune imbalance Mobilization Conditioning Immune resetting and rebalancing Weeks –4 –2 –1 0 4 26 52 report their outcomes to the EBMT (or equivalent profes- Importantly, patients should ask about short- and long- sional society) and maintain their professional competencies term side-effects of the treatment and the level of risk of in this highly specialized field. EBMT membership infor- death from the treatment and the severe AD to make a mation is available from www.EBMT.org and accreditation balanced decision. Patients should ask their transplant and status on www.JACIE.org websites. disease specialists about the experience of their transplant General information for patients and carers considering haematopoietic stem cell transplantation (HSCT). . . 937 unit in general, whether the transplant unit is accredited (by may not only have financial implications, but there may be JACIE, FACT or equivalent) and their specific experience exposure to unnecessary risks to their health and well-being. of treating your particular AD with HSCT. Ideally, the If treatment is unavailable in a patient’s home country, it is transplant centres should have accreditation and have a more satisfactory if they travel and receive treatment with good track record of experience and academic publication in the full support of a disease specialist and transplant spe- the disease for which HSCT is being considered. cialist who knows them well and is familiar with the Patients may also want to ask for an independent spe- centre providing the treatment, or at least their general cialist opinion or whether their case has had a documented practitioner. This may enable direct communication with discussion with a wider group of professionals within a transplant and disease specialist teams undertaking the multidisciplinary team setting (i.e., an MDT meeting). transplant. Independent self-referral by patients is strongly Ideally patients should be seen and followed up in a com- discouraged. bined clinic involving both disease and transplant specia- Even if the initial phase of the transplant is a success, lists. Updates on specific ADs are provided on the EBMT patients should be aware that risks of treatment, such as websites listed at the end of this position statement. infection and organ damage, last for many months and, in One exception for being treated outside established some cases, years after the transplant procedure. As with guidelines is treatment on a clinical trial approved by a HSCT in other settings, ongoing follow-up and support is research ethics committee (REC) or institutional review recommended, along with the need for rapid self-referral to a board (IRB), which may, for example, be testing whether a locally available transplant or other specialist haematology new technique might provide an advantage over existing unit in case of infections or other emergencies. The follow-up treatments. In this instance, patients will be counselled and should include the provision of monitoring for ‘late effects’ of asked to provide an informed consent for the trial. HSCT. These aspects of essential care may be compromised Even if patients are not on a clinical trial, full informed if initial HSCT treatment is delivered outside of their home consent for treatment and also for data reporting is an EBMT country, especially if communication between clinicians is requirement for good clinical practice and data protection. In limited. It is, therefore, important that patients specifically order for the transplant community to gain a better under- address these issues prior to HSCT treatment as they may standing of the long-term side-effects of this treatment, it is require ongoing engagement with clinical services near their important that transplant centres report data relating to home (in both planned or unplanned settings, i.e., emergency transplant treatments to the EBMT or an equivalent registry. or urgent care). In the EBMT, patient data will be handled in an anonymous Following return to home, some health services may not (and/or pseudonymised) fashion and in line with current support monitoring and follow-up following HSCT, general data protection regulation (GDPR). and this may lead to further financial commitment from Figure 3a–d summarises recent activity and JACIE the patient. The EBMT therefore recommend that before accreditation status in EBMT reporting centres for autologous proceeding to transplants, patients carefully assess HSCT procedures in ADs, both overall and for specific dis- arrangements and support for medium- and long-term ease categories. The information is primarily intended as a monitoring and follow-up in their locally available health resource for clinicians in transplant centres and disease spe- services. cialists who wish to make contact with experienced EBMT centres for advice, support, referral or other partnership Summary arrangements aimed at optimising patient care whilst accommodating geographical considerations. The information ● Haematopoietic stem cell transplantation (HSCT) has may also be useful to patients and other carers; however, been used in patients with severe autoimmune and independent self-referral is strongly discouraged. inflammatory diseases whose response to standard treatment options has been limited and associated with a poor long-term prognosis in terms of survival and/or Treatment abroad disability. The vast majority of patients have received autologous HSCT, with the use of allogeneic HSCT Patients should do their best to enquire whether treatment is being rare and mainly in paediatric patients. available within their own health service, and, if not, they ● Although a wide range of autoimmune diseases have should question why. It may be that treatment is available been treated, the evidence base is greatest for the use of under specific circumstances that do not cover specific types autologous HSCT in relapsing remitting MS, diffuse of AD or a disease specialist may not consider it a best systemic sclerosis and Crohn’s disease. option. If treatment is planned outside of their home country ● HSCT may work by ‘re-setting‘ or ‘re-booting’ the patients should think carefully about their decision, as it immune system, which in turn may lead to improvement H. Jessop et al. 4 4 2 64 64 33 Centre activity, MS and other neurological AD, 2012-2017 (≥5 autologous HSCT procedures) IC 3 IC 82 IC 9 *-C 20 *-C IC 2 o* -C 28 us C us nt IC Centre activity for rheumatological AD, 2012-2017 (≥3 autologous HSCT procedures) lni CI 5 lni *-C 3 ra -C Other neurol disorders Vi n*- 30 Vi cia 81 g* Centre activity for AD overall, 2012-2017 (≥10 autologous HSCT procedures) To or 3 ide IC 92 len CIC 7 eb 76 *JACIE accreditation Le *-C C 3 4 Va o*- 19 et IC Centre activity, MS and other neurological AD, 2012-2017 (≥5 autologous HSCT procedures) *JACIE accreditation o rin -C 61 I ila n CI C 34 2 4 65 Go * -C To mo* IC Centre activity for rheumatological AD, 2012-2017 (≥3 autologous HSCT procedures) M n*- IC on 02 ler g*- C e rg re- *-CI C C nd 2 Centre activity for AD overall, 2012-2017 (≥10 autologous HSCT procedures) Other rheumatological AD 24 Lo C Pa bur IC 1 Be o CI 4 Other AD ap ecc 37 e l*- 62 m -C ng se CI C Ha um* 07 206 Si e~L IC 7 Ba NMO s e- *JACIE accreditation ch IC 2 CIC C 0 ) us CD Bo ica a- 74 ulo 5 *-C n* - Tr lon IC (Ped 23 ris ge 09 p To IC m g-C 11 -C 30 4 Pa nha C 2 89 Pa pin C 4 lo* pe CI ko CI 5 IC 2 Os -C Co en*- CIC Lin w- 0 4 e* 4 uv g* - 63 co IC 3 52 nz 64 CIDP os re SSc Le bor IC 6 M o*-C -CIC 89 Fi IC 12 MG MS e 7 *-C IC 7 et *-C 23 rin rg* 2 us Go ncia IC To lbe -CIC 206 lni *-C Vi rg SSc le n*-C 5 ide rg* IC bu MS 9 Va e 6 He ebo n*-C rz 23 eg IC 2 223 et ge 92 ue IC 2 jm W t*- C 67 Ni o*-C CIC 24 Go nha IC 3 ch IC n - 4 ila n* 5 pe -C 61 re -C 4 M nge -CIC Co mo* IC Ut rg 52 i ou IC eb rg * ler *-C 63 ra sb *-C Tu lbe 283 4 Pa burg IC 6 St rg 7 ide IC 21 m -C lbe 67 He *-C CIC Ha ia* 3 ide IC c 28 7 He ce-C 3 nd a*- 17 len C 1 Lu n 2 Va *-CI C 2 wi 20 elo IC I 78 to rc -C 05 nd -C Ka *-CI C Ba va* IC 2 Lu va* IC 7 n 12 4 no -C 78 no *-C 8 ide IC Ge on* C 7 I Ge ield 38 Le *-C f nd *-C 212 ef CIC 05 um 07 Lo ld C Sh y- 2 ch 2 fie -CI 4 e C Bo IC ef * dn CI 04 Sh olm C 3 0 Sy n*- 3 *-C 5 k I o C 2 ris 26 oc *-C 763 nd CI 21 Pa IC 7 St e Lo e*- IC -C 23 nz IC nz *-C 3 n* IC re -C 266 re 6 ila -C Fi on* Fi olm C 7 M e n* 22 3 C k I 66 nd CI oc -C eg IC Lo la*- 388 St on* IC 2 jm -C a Ni en ps CIC 77 nd -C 77 ing 8 Up ey- IC 6 Lo ala* C 6 eb 38 I IC dn -C ps -C Tu -C Sy ice Up ice ey to w to w dn Ka Ka Sy 120 100 80 60 40 20 0 120 100 80 60 40 20 0 30 20 10 0 Auto-HSCT a b c Auto-HSCT Auto-HSCT 938 General information for patients and carers considering haematopoietic stem cell transplantation (HSCT). . . 939 d Centre activity for gastrointestinal AD, 2012-2017 (≥2 autologous HSCT procedures) 20 Crohn Coeliac disease *JACIE accreditation 15 Auto-HSCT 10 5 0 Ba Le Ed M M Lo No Am Co Lo Ga Lu Ni Pr ila ad eu ag uv nd nd eb rc inb ttin rd lw st e no rid elo we ue en ob on on ec ay ur gh rd *-C *-C -C *-C k- a- -C ge *-C *-C na gh am am CI CI IC IC IC in- *-C IC *-C IC IC IC C *-C * C -C CI 31 40 26 61 IC 20 IC 76 76 36 23 C IC IC 8 8 5 5 9 3 8 7 21 22 8 20 71 58 4 8 0 7 8 Centre activity for gastrointestinal AD, 2012-2017 (≥2 autologous HSCT procedures) Fig. 3 a–d Activity and JACIE accreditation status in EBMT reporting as a resource for clinicians in transplant centres and disease specialists centres for autologous HSCT in autoimmune diseases. a Overall. b MS who wish to make contact with experienced EBMT centres for advice, and neurological diseases. c Systemic sclerosis and rheumatological support, referral or other partnership arrangements aimed at optimising diseases. d Crohn’s disease and gastrointestinal diseases. Activity is patient care whilst accommodating geographical considerations. The for autologous procedures from 2012–2017 inclusive, i.e., reflecting information may also be useful to patients and other carers; however, practice after the publication of EBMT ADWP Guidelines [12]. independent self-referral is strongly discouraged. MS multiple sclero- Accreditation status is indicated by asterisks as active and/or with re- sis, SSc systemic sclerosis, CD Crohn’s disease, MG myasthenia accreditation in progress as per December 2018 (www.JACIE.org). gravis, CIDP chronic inflammatory demyelinating polyneuropathy, Centre identities according to CIC code are available on https://www. NMO neuromyelitis optica ebmt.org/ebmt-membership-list. The information is primarily intended in damaged organs and tissues. HSCT works best if ● The EBMT and other professional societies have active inflammation can be switched off, but the summarised the evidence and produced guidelines and effect of HSCT may be limited (or no benefit at all) if recommendations as a resource to support centres and there is no active inflammation. There is no proof that good clinical practice. the blood stem cells can directly rebuild specialised ● HSCT should be conducted in accredited units with tissues, although the absence of inflammation may robust arrangements for early referral for urgent care enable some damaged tissues and organs to heal over after the transplant and long-term follow up with both time. disease and transplant specialists. Centres should ● Compared with most standard treatments, HSCT is routinely submit data on transplanted patients to associated with greater short-term risks, including a risk international registries, such as EBMT. of treatment related mortality (TRM), and long-term ● Treatment and follow-up on a clinical trial should complications (so called ‘late effects’) due to the always be considered, if available within a reasonable intensity of the treatment. The risk of complications is geographical reach of the patient’s home. higher with autologous HSCT in some types of diseases ● Patients considering HSCT treatment abroad for their and in allogeneic HSCT. Risks increase with age, more AD are strongly advised to ensure that expectations in advanced disease and the presence of other conditions this position statement are met by the centre offering which affect patients’ fitness. Decisions should be treatment and that robust referral and follow-up individualised for each patient. arrangements are made with their local disease and ● Before decisions to proceed with HSCT can be made, it transplant specialists. Independent self-referral is strongly is essential to carry out a careful joint appraisal of discouraged. potential benefits and risks by disease and transplant specialists working closely together with patients and carers. Alternative non-transplant treatments should Acknowledgements We acknowledge the support of Eoin McGrath, JACIE Operations Manager. always be a consideration in decision-making. 940 H. Jessop et al. Compliance with ethical standards The EBMT patient, family and donor committee https://www.ebmt.org/patient-family-and-donor- Conflict of interest JAS declares honoraria for speaking at educational committee meetings from Sanofi, Jazz, Janssen and Mallinckrodt. The remaining The objectives of the EBMT patient, family and donor authors declare that they have no conflict of interest. committee include supporting national patient advocacy Publisher’s note: Springer Nature remains neutral with regard to groups, providing a pan-European platform for patient jurisdictional claims in published maps and institutional affiliations. advocacy groups including a patient dedicated link on EBMT website and providing advice on how to optimise Open Access This article is licensed under a Creative Commons EBMT patient centred activities. In addition, the committee Attribution 4.0 International License, which permits use, sharing, aims to increase the numbers of international patients, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the family members and donors to access the EBMT patient, source, provide a link to the Creative Commons license, and indicate if family and donor day at the annual meeting by promoting changes were made. The images or other third party material in this the use of online webcasts and translation. article are included in the article’s Creative Commons license, unless Joint Accreditation Committee ISCT-Europe & indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended EBMT (JACIE) use is not permitted by statutory regulation or exceeds the permitted https://www.ebmt.org/accreditation/about-jacie use, you will need to obtain permission directly from the copyright https://www.ebmt.org/information-patients-donors holder. To view a copy of this license, visit http://creativecommons. JACIE develops and maintain global standards for the org/licenses/by/4.0/. provision of quality medical and laboratory practice in cellular therapy. Based on these standards, JACIE offers accreditation to transplant programmes in order to encou- Appendix rage health institutions and facilities to establish and maintain quality management systems impacting on all The EBMT Autoimmune Diseases Working Party aspects of their activities and to engage in continuous (ADWP) improvement. JACIE's primary aim is to promote high- https://www.ebmt.org/working-parties/autoimmune- quality patient care and laboratory performance in collec- diseases-working-party-adwp# tion, processing and transplantation centres through an The EBMT ADWP is dedicated to promoting clinical internationally recognised system of accreditation. activities, teaching and performing translational research. Paris EBMT Office Our focus is mainly on autologous/allogeneic HSCT, More technical information for clinicians, including together with of novel forms of cellular therapy and new contact with key centres, is available from the Paris EBMT immunosuppressive drugs in a specific challenge to induce Office via Manuela Badoglio, ADWP Study Coordinator, tolerance, with the ultimate objective of better under- manuela.badoglio@upmc.fr who has access to haematolo- standing the possibility of resetting the immune response gists and disease specialists working in your region and during treatment of severe autoimmune diseases. The countries via the EBMT registry and can liaise with mem- EBMT ADWP also has the strategic task of interacting with bers of the EBMT. other autoimmune diseases (AD) specialists and their respective scientific societies. The EBMT Nurses Group References https://www.ebmt.org/nurses-group The EBMT Nurses Group (NG) plays an essential role in 1. Alexander T, Farge D, Badoglio M, Lindsay JO, Muraro PA, Snowden JA. Autoimmune Diseases Working Party (ADWP) of haematology and haematological stem cell transplantation the European Society for Blood and Marrow Transplantation nursing. The group was created 33 years ago and now has (EBMT). Hematopoietic stem cell therapy for autoimmune dis- over 750 members in more than 60 countries worldwide eases - Clinical experience and mechanisms. J Autoimmun. 2018; with a principal nurse identified in almost each EBMT S0896-8411:30182–3. 2. Snowden JA, Sharrack B, Akil M, Kiely D, Lobo A, Kazmi M, et al. centre. The EBMT NG’s mission is to enhance and value Autologous haematopoietic stem cell transplantation (aHSCT) for the nurses’ role all over the world, supporting and sharing severe resistant autoimmune and inflammatory diseases; a guide for knowledge through communication, advocacy, research, the generalist. Clin Med (Lond). 2018;18:329–34. training and education. The group is dedicated to improving 3. Mancardi G, Sormani MP, Muraro PA, Boffa G, Saccardi R. Intense immunosuppression followed by autologous haematopoietic stem the care of patients receiving stem cell transplantation and cell transplantation as a therapeutic strategy in aggressive forms of works towards promoting excellence in care through multiple sclerosis. Mult Scler. 2018;24:245–55. recognizing, building upon and providing evidence-based 4. Michelle Kenyon & Aleksandra Babic Editors. The European practice. Blood and Marrow Transplantation Textbook for Nurses: Under General information for patients and carers considering haematopoietic stem cell transplantation (HSCT). . . 941 the Auspices of EBMT. This Springer imprint is published by the 11. Snowden JA, Badoglio M, Labopin M, Giebel S, McGrath E, registered company Springer International Publishing AG part of Marjanovic Z, et al. European society for blood and marrow Springer Nature (Switzerland) open access. ISBN 978-3-319- transplantation (EBMT) autoimmune diseases working party 50025-6 ISBN 978-3-319-50026-3 (eBook). https://link.springer. (ADWP); EBMT paediatric working party (PWP); joint accred- com/book/10.1007/978-3-319-50026-3. itation committee of the international society for cellular therapy 5. Passweg JR, Baldomero H, Bader P, Basak GW, Bonini C, Duarte (ISCT); EBMT (JACIE). Evolution, trends, outcomes, and eco- R, et al.; European Society for Blood and Marrow Transplantation nomics of hematopoietic stem cell transplantation in severe (EBMT). Is the use of unrelated donor transplantation leveling off in autoimmune diseases. Blood Adv. 2017;1:2742–55. Europe? The 2016 European Society for Blood and Marrow 12. Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Transplant activity survey report. Bone Marrow Transplant. 2018 Cervera R, et al. on behalf of the EBMT Autoimmune Disease https://doi.org/10.1038/s41409-018-0153-1. [e-pub ahead of print]. 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Update of EULAR research and treatment of cancer (EORTC), the immunocompro- recommendations for the treatment of systemic sclerosis. Ann mised host society (ICHS) and the European leukemianet (ELN). Rheum Dis. 2017;76:1327–39. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia 16. Sullivan KM, Majhail NS, Bredeson C, Carpenter PA, Chatterjee in patients with haematological malignancies and stem cell trans- S, Crofford LJ, et al. Systemic sclerosis as an indication for plant recipients. J Antimicrob Chemother. 2016;71:2397–404. autologous hematopoietic cell transplantation: position statement 9. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tom- from the American society for blood and marrow transplantation. blyn M, et al. Infectious diseases society of America.2013 IDSA Biol Blood Marrow Transplant. 2018;S1083-8791:30362–8. clinical practice guideline for vaccination of the immunocom- https://doi.org/10.1016/j.bbmt.2018.06.025. promised host. Clin Infect Dis. 2014;58:309–18. 17. von Wunster B, Bailey S, Wilkins A, Marks DI, Scolding NJ, Rice 10. Snowden JA, McGrath E, Duarte RF, Saccardi R, Orchard K, CM. Advising patients seeking stem cell interventions for multiple Worel N, et al. JACIE accreditation for blood and marrow sclerosis. Pract Neurol. 2018. pii: practneurol-2018-001956. transplantation: past, present and future directions of an interna- https://doi.org/10.1136/practneurol-2018-001956. [e-pub ahead tional model for healthcare quality improvement. Bone Marrow of print]. Transplant. 2017;52:1367–71. Affiliations Helen Jessop1 Dominique Farge 2,3,4,5 Riccardo Saccardi6 Tobias Alexander7 Montserrat Rovira8 ● ● ● ● ● Basil Sharrack9 Raffaella Greco10 Nico Wulffraat11 John Moore12 Majid Kazmi13 Manuela Badoglio ● ● ● ● ● 14 ● Gillian Adams15 Bregje Verhoeven15 John Murray16 John A. Snowden 1 ● ● ● 1 Department of Haematology, Sheffield Teaching Hospitals NHS 4 EA 3518, Université Denis Diderot, Paris 7, France Foundation Trust, Sheffield S10 2JF, UK 5 2 Department of Internal Medicine, McGill University, Unité de Médecine Interne: Maladies Auto-immunes et Pathologie Montréal, Canada Vasculaire (UF 04), Hôpital St-Louis, AP-HP, 1 avenue Claude 6 Vellefaux, Paris, France Haematology Department, Careggi University Hospital, 3 Florence, Italy Centre de Référence des Maladies auto-immunes systémiques Rares 7 d’Ile-de-France, Filière FAI2R, Paris, France Klinik fur Rheumatologie und Klinische Immunologie, Charite- 942 H. Jessop et al. Universitatsmedizin, Berlin, Germany Netherlands 8 12 Department of Haematology, Institute of Haematology and Department of Haematology, St Vincents Hospital Sydney, Oncology, IDIBAPS, Hospital Clinic, University of Barcelona, Darlinghurst, NSW, Australia Josep Carreras Leukaemia Research Foundation, Barcelona, Spain 13 Kings Healthcare Partners, Department of Haematology, Guys 9 Department of Neurology, Sheffield Neuroscience BRC, Sheffield Hospital, London SE1 9RT, UK Teaching Hospitals NHS Foundation Trust, University of Sheffield, 14 Sheffield S10 2JF, UK EBMT Paris study office/CEREST-TC, Department of Haematology, Saint Antoine Hospital – INSERM, Paris, France 10 Hematology and BMT Unit, San Raffaele Scientific Institute, Via 15 Olgettina 60, 20132 Milano, Italy EBMT Executive Office, Eddific Dr. Frederic Duran i Jorda, Passeig Taulat, 116. 08005, Barcelona, Spain 11 Divisie Kinderen, Cluster Immunologie, Reumatologie, Hematologie 16 en Infectiologie, Wilhelmina Kinderziekenhuis, Utrecht, The Christie Hospital NHS Foundation Trust, Manchester, UK