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Report of the Transplant Complications Working Party Educational Meeting - 14-16 September 2023 - Copenhagen, Denmark

Transplant Complications Working Party (TCWP)

Summary report written by Ivan Moiseev, TCWP Secretary, RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russian Federation

This year, the Transplant Complications Working Party Educational Meeting followed a fine established tradition of very practical educational meetings. Experts among physicians, nurses and patient advocates shared their expertise in decision-making for major hematopoietic cell transplantation (HCT) and CAR-T complications. The sessions were organized as panel discussions based on clinical case presentations. The vast majority of topics regarding complications were covered, including patient path through HCT, graft-versus host disease (GVHD), veno-occlusive disease (VOD), transplant-associated microangiopathy (TMA), late events, survivorship, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The meeting program also incorporated “difficult patient” cases from young physicians, Sheila Torrado Gonzalez, Julio Ropero, Sharon Lionel and Jonas Wißkirchen, which were chosen from a number of submitted cases and awarded with a travel grant.  

The meeting started with a welcome from Zinaida Peric and Ivan Moiseev, introducing TCWP activities and an overview of the program, and Lars Klingen Gjærde welcoming everyone to Copenhagen. This year the meeting had more than 40 registered physicians and nurses.  

Patient journey through allogeneic transplant complications by Lars Klingen Gjærde, Henrik Sengeløv, Ann-Mari Berthelsen, Jacob Riedel Svendsen.

The discussion panel started by Lars Klingen Gjærde presenting the path of a patient to transplant in Denmark, including the mechanisms of initial referral, decision to transplant a patient, amount of information provided to a patient before and during transplantation. Panel members and attendees shared their experience on approaches to providing information about complications and HCT procedures. The panel covered aspects of shared responsibility on decision to transplant and establishment of a trusting relationship between a patient and a transplant team. Henrik Sengeløv presented a case with multiple complications requiring long care in the HCT clinic and a long rehabilitation process. Panel members discussed how to support and move a patient towards re-socialization in the case of multiple complications. The importance of transparent patient-physician relationship was highlighted. Then patient advocate Jacob Riedel Svendsen told his story of going through early complications and chronic GVHD. He emphasized the importance of exercise, support of family and friends, early return to work and occupational activities and coping strategies that a medical care provider can advise to their patient. Ann-Mari Berthelsen shared her experience on interaction with a patient and patient’s family during evaluation by nursing stuff before and after HCT and aspects that doctors sometimes miss.

Sheila Torrado Gonzalez presented a case of pediatric acute lymphoblastic leukemia undergoing second HCT after multiple lines of therapy. The patient had various complications including veno-occlusive disease, sepsis, viremia, cytopenia. The panel members suggested the approaches to optimize treatment and prognosis in such patients.    

Patient journey through GVHD by Hildegard Greinix, Daniel Wolff, John Murray, Andrea Linke

The session was started by Hildegard Greinix who, with patient examples, showed how to diagnose and stage acute GVHD, distinguish overlap and late acute GVHD from chronic. Approaches to second-line treatment were presented, including selection between ruxolitinib, extracorporeal photopheresis (ECP) and other anti-cytokine therapies. Focus was made on assessment of response. Panel members shared their experience in acute GVHD. Daniel Wolff continued with case-based discussion of chronic GVHD covering atypical manifestation and recently published consensus on uncommon organ involvement. Goals of therapy and evaluation of response in chronic GVHD were covered. Special focus was made on genital chronic GVHD, which is often missed during evaluation. Daniel Wolff highlighted the importance of timely evaluations of response, selection of agents based on current recommendations and presented a difficult case with neglected manifestations of lung GVHD that could be avoided. During these case presentations, John Murray shared his professional tricks during evaluation of chronic GVHD with a focus on symptoms, which patients tend to underreport. Patient advocate Andrea Linke during the session shared her personal experience of going through GVHD and importance of actively discussing with a patient such manifestations as fatigue, sexual problems and disability to perform routine daily activities.

The session was concluded by presentation of selected case by young physician Pedro Baptista. He presented the case with steroid-refractory chronic lymphocytic leukemia patient with steroid-refractory gastrointestinal grade III acute GVHD and persistence of minimal residual disease (MRD). The case describes efficacy of ECP and mycophenolate mofetil combination to achieve complete response of acute GVHD while maintaining graft-versus-leukemia effect and facilitating MRD-negative status.

Patient journey through early complications after alloSCT by Ivan Moiseev, Daniele Avenoso, Sophie Van Lancker, Michelle Kenyon

Daniele Avenoso started the session by presenting the case of the patient with myelodysplastic syndrome. With this case, he went through major VOD risk factors, early signs and grading of VOD and indications for treatment. The panel discussed the importance of extended ultrasound evaluation, utility of biomarkers and specific clinical signs that should noticed by nursing stuff and doctors early on in pediatric and adult patients. Daniele Avenoso discussed with the panel practical aspects of response evaluation and adverse events of defibrotide treatment. The session was continued by Ivan Moiseev, who showed the case of TA-TMA, involving early signs, aspects of new Harmonization consensus criteria, histological evaluation, and differential diagnosis. Interaction with the audience and nurses highlighted the need for additional education in this complication. Several approaches to treating TA-TMA were discussed, like switching calcineurin inhibitors to other agents and administration of anti-complement therapies.

The session was concluded by Julio Ropero presenting a case of the pediatric patient with acute lymphoblastic leukemia developing severe TA-TMA with multiorgan failure. The characteristic feature of this case was the presence of C3 mutation, resistance to immunosuppression modulation and eculizumab and response to narsoplimab. The case highlights the possibility of break-through TA-TMA manifestations during C5 blockade, like those happening in paroxysmal nocturnal hemoglobinuria.

Coaching session to foster patient-centred survivorship care by Hélène Schoemans, Zinaida Peric, Kristina Nørskov, Elke Stienissen

During the session, patient advocate Elke Stienissen and Helene Schoemans gave a unique perspective on late complications both from the point of view of physicians and patients. With an interactive case, the session gave an overview of quality of life, secondary malignancies and their screening, fertility and social rehabilitation, sexual life of survivors and aspects of returning to work and social life. This session covered usually underestimated and underreported problems like fatigue, chronic anxiety, problems with social contacts and maintaining family relationships. Various tools for patient-reported outcomes were discussed. The importance of building trustful relationships between transplant center and local care provider was illuminated. Kristina Nørskov also shared her experience in building long-term relationships and asking uncomfortable questions during nurse-patient interactions through long-term care. 

The session ended by presentation of the case by Sharon Lionel, who described very late onset post-transplantation lymphoproliferative disorder with solely bone marrow involvement starting from unusual fatigue, fever and cytopenia. The case illustrated the successful story of fast diagnosis and cooperation between local medical care providers and transplantation clinic.

Industry Symposium kindly sponsored by Therakos "Understanding the evolving practices of utilising ECP in the current treatment of GvHD” by Therakos.

Industry symposium was presented by Olaf Penack and Robert Zeiser and the main focus of it was on combination regimens involving ruxolitinib and ECP. Olaf Penack started the session by overview of novel EBMT recommendations on GVHD that will be published in 2023. He highlighted based on current evidence ruxolitinib, while not still available in some countries, should be the first choice of therapy. Then he presented the study based on expert panel answers demonstrating that there is still a subgroup of patients where ECP can be the first choice over ruxolitinib and presented the situations where experts deemed combination therapy with ECP appropriate. Then Robert Zeiser shared his experience with ECP-ruxolitinib combination in second line as well as ruxolitinib-refractory cases responding to ECP addition to therapy. The speakers emphasized a very good safety profile of combination treatments. The speakers and audience discussed the advantages and risks of multiple therapies used at once for chronic GVHD.    

Impact of novel tools on complication management: artificial intelligence and more by Amin Turki, Shahrukh Hashmi

The second day started with the session on artificial intelligence (AI) tools that can help physicians in decision making. Amin Turki went through the currently existing body of evidence supporting the use of AI for HCT complications. He demonstrated the importance of not only pre-transplant data, but also incoming laboratory and clinical data during transplant to reach high probability of prediction. Shahrukh Hashmi has given his perspective on the path to implementation of AI tools. He emphasized the importance of clinical study to test AI efficacy like for any other medical drug or device. Nonetheless he acknowledged the difficulties to go through randomized trials with AI tools, given their heterogeneity and fast development. Shahrukh Hashmi presented the number of AI tools that are either already registered in the US for medical use or are approaching registration. The session was concluded by discussing the importance of ethical considerations when implementing AI tools in the HCT field, since information provided by AI to patients may cause additional distress during transplant.

Patient journey through CAR T-cell therapy. Practical guide to managing CAR-T complications by Christian Schultze-Florey, Olaf Penack, Christian Könecke, Ruth Clout

The session was started by Christian Könecke. Based on interactive cases he presented the approaches to staging CRS, changing landscape of therapies for CRS, more extensive and early use of steroids, anakinra and ruxolitinib. Christian Könecke then presented the clinical manifestation of macrophage activation syndrome, and key laboratory and clinical features necessary to recognize them. The session was continued by Christian Schultze-Florey who demonstrated a case of ICANS, how to evaluate mental status in patients with ICANS, how to choose therapy based on the results of mental screening tests and when to switch to second line therapies. Christian Schultze-Florey presented the results of second-line anakinra for ICANS and stated the importance of using high doses of this agent upfront. The importance of monitoring for other complications like Parkinson’s-like syndrome after anti-BCMA CAR-T was stated. The session was continued by Olaf Penack giving an overview on the problem of cytopenia after CAR-T. He presented the results of the study evaluating practices in cytopenic patients after CAR-T, the use of boost, growth factors and the timing for intervention. The current body of evidence indicates that intervention for grade for 4 cytopenia is required as early as 2 weeks after the start of this complication. The panel discussed the use of primary antibacterial and antifungal prophylaxis in this group of patients. During the session Ruth Clout shared her experience on monitoring CRS and ICANS from the nurse perspective.

Nurse's perspective

Summary report written by Sophie Van Lancker, TCWP Nurse Representative, Ghent University Hospital, Belgium

Besides a large representation of doctors and junior doctors, a nice number of nurses and patient advocates were present. As a result, the discussions were viewed from a multidisciplinary angle.

Each part of the sessions was guided by a panel including a doctor, a nurse and a patient.

A trainee doctor could present a difficult case after which there was reflection on whether a different approach would be possible, whether other options would have been taken. This is very valuable also for nurses. As a nurse you discover this way that the therapy given can be very diverse depending on a lot of individual factors, as well as factors that are pharmaceutically guided, experience of the local doctor.

The TCWP is engaged in developing studies in different subfields regarding complication after stem cell transplantation or CAR T. The meeting was also divided in this way.

The first session involved a patient journey through allogeneic transplant complications.

The path of a transplant of a patient in Denmark was presented. Afterwards there was a good discussion between physicians, nurses and patient advocates about the amount of information, the time to give the information. In the same session, a physician guided us through a journey of a patient with multiple complications. The session ended with a story told by a patient. He underlined the importance of family, friends, early re socialisation and the importance of having a good relation with you physician, post-transplant team. The nurse in this session talked about the importance of information given by the nursing staff to the patient and his family.

The following session guided us through different aspect of GvHD and the new approaches and therapies. Important to remember is that some GvHD signs are under reported like male genital GvHD but also changes in taste, changes in view.

Next session was focused on early complications like VOD, TMA and how to diagnose. The importance of the timing of the ultrasound, biomarkers, was highlighted and also the role of the nurse to foresee a good fluid balance and observation of the patient.

At the end of the day, a patient advocate gave a clear overview of complications she struggled with after an allotransplantation. She shared her thoughts and feelings that there is an underreporting of fatigue, anxiety, social rehabilitation and maintaining relationships next. This is something, nurses in the ward, are not knowing enough of it. There is a life after HSCT, but mostly not the same life as before. The question could be if patients want to know this up front or not. In one of the other sessions the patient advocates asked that you poll this in earlier patient contacts, so you can give advice on demand.

This is a meeting that is accessible for nurses. I hope that next year, more nurses can join this meeting. It is a good method to go into discussions with other caregivers, other centre and not at least with long term survivors.