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Report of the Autoimmune Diseases Working Party Educational Meeting – 22-23 September 2022 - London

Autoimmune Diseases Working Party (ADWP)

Summary report written by:

Giacomo Boffa Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, IT
Gavin Brittain Department of Neurosciences, University of Sheffield and Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
Giorgio Orofino Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milano, Italy; San Raffaele Vita-Salute University, Milano, Italy
Rhiannon Sweeney Staff Nurse, Haematology, Department of Specialised Medicine and Communicable Diseases, Sheffield Teaching Hospitals, Sheffield, United Kingdom
Davide Bonomi Staff Nurse, Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milano, Italy

ADWP Educational Meeting 2022_Group Photo

Scientific session I: Hematopoietic Stem Cell Transplant (HSTC) activity – Update from the EBMT registry

Raffaella Greco (IT) gave an update from the EBMT registry on the use of HSCT for autoimmune disorders. The evolution, the trends, and the primary indications of HSCT in the last years were discussed. The activity of countries and centres collaborating to the EBMT registry have been presented. It has been noted that multiple sclerosis and systemic sclerosis are the fastest growing indication for HSCT in this field. The possibility in the next future of delivering more advanced cellular therapies, such as regulatory T cells and CAR-T cell therapies, in patients affected by autoimmune disorders, has been finally discussed.

Scientific session II: Immunologic mechanisms

Chairs: Paolo Muraro (UK) & Jörg Henes (DE)

Maria Teresa Cencioni (IT) gave an overview of the current knowledge on the immune reconstitution processes after aHSCT in people with multiple sclerosis. It has been highlighted that although immune reconstitution has been extensively studied for T cells, only limited evidence exists for the B cells compartment. Preliminary data on B cell renewal in people with multiple sclerosis have been presented, showing that naïve B cells are predominant in the first years after aHSCT and present regulatory, anti-inflammatory characteristics.

Josefine Ruder (CH) presented new data on the dynamics of the immune reconstitution after aHSCT in people with multiple sclerosis, highlighting that it consists of a multi-phase process, with an expansion of pre-existing, exhausted effector memory T cells in the early phase and a later renewal of naïve T cells through increased thymic output.

Marc Schmalzing (DE) gave an overview of the immunological adverse events after HSCT in systemic sclerosis, with a special focus on engraftment syndrome and secondary autoimmune disorders. Risks factors, incidence, treatment strategies and outcomes were discussed.

Kelen Cristina Ribeiro Malmegrim de Farias (BR) presented data on the immune reconstitution after aHSCT in people with systemic sclerosis. She reported that naïve B cells predominate after aHSCT, showing improvements in immunoregulatory and anti-fibrotic mechanisms, which may contribute to re-establishment of self-tolerance and clinical remission.

Matteo Doglio (IT) gave an account of the incidence, the risk factors, and the clinical characteristics of hemophagocytic lymphohistiocytosis after HSCT and CAR-T cells therapy. Although it represents a rare adverse event in these settings, there is need for evidence-based approaches to the recognition and treatment of hemophagocytic lymphohistiocytosis following HSCT and CAR-T cell therapy.

Session III: Mobilization and conditioning regimen in HSCT for autoimmune diseases: how can we adapt it to improve outcomes?

Chairs: John Snowden (UK) & Matilde Inglese (IT)

Basil Sharrack (UK) reviewed the evidence free zone of the impact of disease modifying therapies (DMT) on mobilisation outcomes and considerations for washout periods in multiple sclerosis. It is theorised that prior DMT use may influence mobilisation of stem cells, although little has been studies previously. The raft of new DMTs were outlined and the wide spectrum of washout periods used in previous trials, including MIST, and current trials discussed. There is a need for a formal study to advance our understanding.

Riccardo Saccardi (IT) gave an account of the various conditioning regimens used during autologous transplantations for patients with multiple sclerosis. In general, there has been a move to intermediation conditions regimens with cyclophosphamide and anti-thymocyte globulin (Cy + ATG) showing low transplant related mortality, in parallel with the BEAM plus ATG regimen (carmustine -BCNU, etoposide, cytarabine and melphalan). CD34 graft selection is controversial among studies.

Jaap van Laar (NL) presented the various conditioning regimens used in autologous transplantations for patients with systemic sclerosis. Whilst there is no significant difference in outcomes between lymphoablative and myeloablative regimens, there does appear to be a reduced relapse rate following adjunctive rituximab. It is unclear whether CD34 graft selection alters outcome. The importance of cardiopulmonary screening during patient selection was highlighted and patients who have never smoked and have a body mass index within normal range doing better.

Raffaella Greco (IT) provided an update on allogeneic haematopoietic stem cell transplantations for autoimmune diseases. Allogeneic transplantation has been used rarely as compared to autologous HSCT within this field, and mainly in the pediatric setting. Previous transplants have been performed across a heterogenous group of diseases, in patients whose condition has been refractory. Drawing on experience from the field of hemato-oncology the move to a reduced intensity/reduced toxicity regimens was highlighted.  In this context, the introduction of post transplantation cyclophosphamide appears to be reducing the incidence of graft versus host disease.

Session IV: State-of-the-art: HSCT for major indications

Chairs: Dominique Farge (FR) & Montserrat Rovira (SP)

Richard Burt (US) provided a comprehensive overview of the 507 cases of multiple sclerosis (MS) treated at a single center level. The experience of a variety of difference regimens was shared and the suggestion that higher doses of ATG and CD34 selection appear to lead to more Epstein-Barr virus reactivations. Overall survival was around 99% at 5 years. Post transplant secondary autoimmune diseases were idiopathic thrombocytopenia (ITP) and hypo or hyperthyroidism. ITP was highest with alemtuzumab-based regimens. Overall, in patients with relapsing remitting MS, autologous non-myeloablative HSCT is an effective one-time therapy.

Nicoletta del Papa (IT) reviewed the use of HSCT in systemic sclerosis. Broadly, the introduction of autologous HSCT (aHSCT) has led to a reduction in all cause mortality. They specifically pointed to the use of aHSCT as an important treatment in patients with interstitial lung disease, although patients should be treated early in their disease course with young age being a protective factor. Adequate patient selection and cardiopulmonary assessment are mandatory in this population.

James Lindsay (UK) provided an overview of the two recent trials of HSCT within Crohn’s Disease (CD). Whilst the first trial was stopped early due to adverse effects, which occurred in a medically refractory group of patients, clinical improvements and endoscopic improvements were demonstrated.

Tobias Alexander gave an overview of the current treatment options available in Systemic Lupus Erythematosus (SLE). With an increasing pool of biologics, recent registry data showed lower HSCT numbers for this indication. Cyclophosphamide and ATG appears to be the regimen of choice due to improved outcomes. Results have demonstrated that CD34 selection reduces relapse rate. The role of HSCT in other rare rheumatological disorders, such as Bechet’s and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, was highlighted.

Session V: Cross-fertilization session

Chairs: Raffaella Greco (IT) ADWP chair & Rafael de la Cámara (ES) IDWP chair

Varun Mehra (UK) introduced the role of EBV and CMV reactivations in patients with MS undergoing HSCT. Few data regarding viral reactivations in autoimmune disease patients are available in literature, even though CMV and EBV disease represent common viral infections in the general HSCT population. Accurate viral monitoring and precocious treatment is essential for preventing the risk of infectious complications.

Malgorzata Mikulska (IT) discussed about the role of viral prophylaxis and vaccination strategy in HSCT recipient, and finally resumed the current challenges associated with Covid 19 pandemic for patients and clinicians involved in the transplant field.

Sofia Forslund (DE) highlighted the importance of microbiome in patients, discussing about the role of the host microbiome in autoimmune diseases, especially the role microbial metabolites involved in disease progression. New microbiome biomarkers predicting outcomes in patients undergoing HSCT may be crucial to forecast the course of the disease.

Andreas Mackensen (DE) introduced his results about CAR T cells in Systemic Lupus Erythematotus (SLE) patients. He described new data about safety and efficacy of anti-CD19 CAR T Cells in SLE patient. CD19 CAR T-cell therapy appears well tolerated and induces rapid remission in patients with severe refractory SLE; 5 out of 5 patients stopped all SLE medications, including steroids, with complete remission of symptoms. Long-term follow up is warranted. This work may pave the role for a new era in autoimmune disease, with CAR T cells potentially available also for other indications in this field.

Parallel nurse section: taking care of HSCT patients with AD

Chairs: Ariadna Domènech (ES) & Helen Jessop (UK)

Gillian O’Dell explained that there are observable differences in the support needs of patients with MS  in the transplant pathway compared with hematological patients. To reduce traveling and the associated burdens, the HSCT process tends to happen in a shorter time frame which gives MS patients less time to come to terms with the process. During admission, mobility and fluid management needs to be closely managed, and require to have physiotherapy involvement from an early stage. The key difference in caring for MS patients is that the ATGs given as part of the treatment regime can cause fevers which can cause pseudo-flare-ups of their prior MS symptoms.  Meanwhile, follow-up needs consist of managing and balancing the combined MS fatigue and HSCT fatigue, improving community services for non-cancers patients, and the remote management of follow-up and finally CMV/EBV monitoring. Finally, it is important nurses are managing patients’ expectations and educate them on the chances of early MS relapse, early menopause, and ensuring fertility reviews are completed.

Iris Cirera highlighted that before HSCT, Crohn’s patients tend to be chemo naïve and require fertility preservation and additional emotional support.

During conditioning, nursing priorities regard monitoring vital signs, daily weights, abdominal perimeter, stools, and fluid balance charts and ensuring daily blood tests and a low bacterial diet are maintained. The main difference between caring for Crohn’s HSCT is that on Day 0, Crohn’s patients should become nil by mouth and commence TPN (hence the need for a three-way CVC) until they have engrafted and should commence prophylactic intravenous antibiotics on Day 1. HSCT-Related complications that nurses need to be aware of are neutropenic fever, infections, perianal abscess, and abdominal sepsis.

Lisa-Marie Heininger and Hahn explained that heart involvement is a common but unrecognized side effect of SSc which makes these patients high-risk transplants. Nursing priorities in this patient regard the risk of malnutrition, skin defects, chronic wounds, and dyspnea. Malnutrition is a side effect, due to swallowing disorders which can be worsened by HSCT, and for this reason, is fundamental to include the nutrition team from an early stage. Due to thick skin caused by high collagen production, SSc patients tend to have skin defects and ulcers, often located at fingertips and elbows, which can worsen during HSCT, therefore nursing staff must be closely monitoring the wounds, involving PT/OT, and assisting with activities of daily living. One of the most severe complications is dyspnea and an increased risk of pulmonary edema and cardiac stress due to fluid overload, which is harder to identify due to the lack of skin edema. Nurses should ensure twice daily weights and maintain a fluid balance to monitor for overload.

Colette Edward’s research has allowed for the formation of recommendations to be applied by nursing staff which include: easier access to psychological support during any stage of treatment, information on possible side effects of treatment, educating patients on the fact that old symptoms of MS may flare up during or post-treatment and for more education to be provided to hematology nursing staff on MS. The main area for improvement Edward’s identified was follow-up post-HSCT, improvements include providing patients with a flow chart of who the key contact is at every stage, clearer communication pathways between the medical team and GPS/ local centers, better communication related to revaccination and information on long term side effects.

Patient, Nurses and Physician Trainee Joint Session

Chairs: Ariadna Domenech (ES), Majid Kazmi (UK) & Rosamaria Nitti (IT)

Helen Jessop explained the design of the study being carried out under the umbrella of the ADWP to collect data on reimbursement of HSCT costs in patients with autoimmune diseases. The importance of being able to complete this study is to have objective data that show the status of this question and whether there are differences between countries despite the existence of clear indications regarding HSCT in autoimmune diseases.

Nina Salooja addressed the preservation of fertility in patients as it is an issue that must be taken into account when we are faced with a patient who is going to receive chemotherapy or undergo an HSCT. In some cases, like in patients with malignant hemopathies, there is no time to address preservation, but in the case of patients with autoimmune diseases it is an issue that we must raise, and it is crucial to discuss the different treatments and options. One of the conclusions we reached after the data offered by Salooja is that although it is an aspect in which we have made progress, we still have room for improvement in how we address this subject among our patients.

Davide Bonomi presented the range of conditioning regimes used to treat AD HSCT patients, the associated toxicities and side effects, and how to manage these from a nurse's perspective.

Bonomi focused on the specific complications for ADs post-HSCT, such as in MS patients who are at an increased risk of falls, requiring ongoing physiotherapy and worsening of neurological symptoms. He also highlighted the increased risk of deep vein thrombosis, caused by immobility, requiring early mobilization and anti-coagulant drugs and urinary tract infections due to the altered balder function and the use of catheters, which should be treated with hydration and anti-microbial drugs. Gastrointestinal toxicity is common post-HSCT, resulting in suboptimal dietary intake which consequently results in 35% of patients becoming malnourished.