Physician Programme
Summary written by Selim Corbacioglu, PDWP Chair; Josu de la Fuente, PDWP Vice Chair and Katharina Kleinschmidt, PDWP Secretary.
The formerly well-established Regensburg’s “Sickle Cell Meeting” has been extended this year to a general meeting on Haemoglobinopathies, organised by the EBMT-PDWP with Selim Corbacioglu (Chair), Josu de la Fuente (Vice-Chair), Katharina Kleinschmidt (Secretary) and Hilda Mekelenkamp (Nurses Group). From November 10-12, more than 130 participants from 24 countries joined to attend this international meeting of experts in the field of hemoglobinopathies. The faculty included around 30 experts and recognized leaders in their respective fields and presented a comprehensive state of the art overview on all important aspects of Sickle Cell Disease (SCD) and thalassemia syndromes.
Thursday, 10th November 2022
The meeting was opened by the welcome words from the chair of the PDWP, Selim Corbacioglu, and started immediately with a fascinating session on “The Genomics of Sickle Cell Disease”, chaired by Lakshmanan Krishnamurti. Josu de la Fuente gave a comprehensive overview on the current natural history of haemoglobinopathies and outcomes of transplantation. It is evident that SCD remains a significant problem in the era of widespread hydroxycarbamide and transfusion therapy, as therapeutic standards of care do not adequately control acute pain events for many patients. Transplantation outcomes are excellent if performed early (before the age of 13) and with an HLA-identical sibling donor, however this “paradigm” is increasingly questioned with the rising experience in haploidentical HSCT. Courtney Fitzhugh reported on clonal evolution in SCD. The observation is that the incidence of hematological malignancy, that ranges around 0.021 per 100 person-years, is highest in adults with graft failure, mixed chimerism and after a treatment of gene therapy. Possible reasons might be an older patient population, more severe disease, longer duration of follow-up and the use of TBI versus Chemotherapy-based conditioning.
As one highlight of the first day, Prof. Douglas Higgs from Oxford University presented a fascinating keynote lecture on “Genomic control of haemoglobin switching”. The enthusiasm of Higgs for science in general and his personal area of research in particular, lead to an excellent lecture on the great variability of possible (re)activation of mostly embryonic globin gene expressions, that might be adopted for treatment for severe forms of a-thalassemia.
Session II then was dedicated to targeted treatment options for hemoglobinopathies. Maria Cappellini from Milan, Italy, joint via video-presentation with new therapeutic options on ß-thalassemia. Several lentiviral trials have been conducted so far, as well as the CRISPR-Cas based concept that is now close to commercialization. Several molecular agents such as Luspatercept, mitavipat and ferroportin inhibitors offer alternatives in treatment, where SCT or gene therapy might not (yet) be feasible. The day closed with the presentation of Miguel Abboud from Lebanon on novel targeted agents for SCD: Exa-Cel (CRISPR-Cas based gene therapy), Voxelotor and GBT02160 as HbS polymerization inhibitors are new “kids on the block” in the treatment of SCD. Furthermore, Inclacumab as a new P-selectin inhibitor is currently being evaluated in phase 3 studies for the reduction of vaso-occlusive crises (VOCs) in patients with SCD. Arginine, targeting the NO pathway, and mitavipat/etavopivat, targeting pyruvate kinase, offer additional options for a pharmaceutical therapeutic approach.
Friday, 11th November 2022
Part 1 of Session III addressed all aspects of gene editing, gene therapy and gene correction. Initiated by Matthew Porteus, the question: “Gene Correction: The gold standard of gene therapy for Sickle Cell Disease?” was actively discussed. In this presentation of high interest, Porteus showed extensively how HR (homologous recombination) based genome editing has tremendous versatility in genome engineering and that it can be used to generate natural human genetic variants. Technological improvements will certainly continue in the upcoming years; yet economical aspects and accessibility need to be discussed. The impact of gene editing is significant even with current conditioning regimens, but might be exponentially broader for genetically engineered HSC therapies when non-chemo based myeloablation becomes available.
Julie Kanter-Washko from University of Alabama Birmingham subsequently presented an update on gene therapy with BBB: Lovo-Cel is a LentiGlobin based approach directed to add a new gene for healthy hemoglobin to stem cells without removing, changing or correcting the HbS gene. The 36 months event-free survival rate was 96.3% (95% CI: 76.5, 99.5) with no graft failure observed. Occurrence of MDS/AML were similar to that seen in autologous transplant setting (in other disorders) and the allogeneic transplant setting in adults with SCD. Josu de la Fuente and Selim Corbacioglu presented furthermore an update on gene editing for SCD and transfusion-dependent-thalassemia (TDT), respectively. In contrast to the BBB approach, Exa-Cel is a therapy that uses non-viral, ex vivo CRISPR/Cas9-mediated editing of BCL11A to increase HbF levels. A single dose of exa-cel lead to an early increase in HbF with consecutive transfusion independence in 42/44 TDT patients and 100% VOC-free survival in 31 SCD patients.
Part 2 of Session III continued with gene editing, gene therapy and gene correction. Stavros Loukogeorgakis from Great Ormond Street Hospital presented an exciting talk on nanotechnology for gene correction. In the setting of HSCT, nanoparticles are aimed to increase homing and the repopulation capacity of transplanted HSCTs.
James Davies from University of Oxford completed this session with an excellent presentation on the development of base editing approaches for haemoglobinopathies and the characterization off-target effects.
During the industry symposium (Vertex), a roundtable discussion considering treatment decisions for patients with haemoglobinopathies was conducted with strong involvement of the audience, leading to an animated discussion between the audience and the speakers.
Session IV was dedicated to all transplant aspects, mainly alternative approaches in hemoglobinopathies. Suradej Hongeng from Ramathibodi Hospital (Mahidol University) presented a comprehensive overview on haploidentical HSCT for TDT patients with the post-transplant Cyclophosphamide (PTCY) approach; the same topic was further discussed in a detailed manner for SCD by Adetola Kassim (Vanderbilt Clinic, Nashville) via video presentation. Erfan Nur from Amsterdam University Medical Centers focused on an almost orphaned patient population, adult SCD patient. Although an allogeneic SCT is feasible in adult SCD patients, concerns about graft failure and poor donor chimerism are emerging. Finding the balance between conditioning toxicity and graft failure represents a particular challenge.
In Part 2 of Session IV, Selim Corbacioglu presented the “T-Haplo for SCD” trial; a phase 2 international multicenter trial to assess haploidentical a/ß T-depleted stem cell transplantation in patients with SCD with no available sibling donor. Based on the data from the pilot study, aß/CD19 T-haplo HSCT showed to be feasible with no acute rejection, and EFS/OS rates similar to outcomes in MSD HSCT. Moreover, very low rates of aGvHD and cGvHD with no significant viral infections render the haploidentical approach increasingly attractive.
During this particularly intense session, Shalini Shenoy from Washington University presented furthermore data on unrelated HSCT in SCD, followed by Suhag Parikh (Atlanta, USA) on cord blood. Satya Yadav from India presented highly relevant data on pre-transplant immunosuppression enabling transplantation in immunized patients. Desensitization with Tacrolimus/MMF, Rituximab, plasma exchange etc. can help to reduce rejection in the high-risk category of TDT patients (class III).
Greg Guilcher, known from the STAR alliance and working at university of Calgary, focused on the non-myeloablative approach in children with SCD, followed by Akshay Sharma (St. Jude Children’s Hospital) who completed the topic of reduced intensity conditioning, reporting that a regimen using alemtuzumab, thiotepa and low dose TBI resulted in reduced toxicity and improved outcomes in patients with SCD.
Saturday, 12th November 2022
In Session V, global curative approaches for HGB were discussed from numerous different perspectives: Abdullah Aljefri presented the Saudi Arabian Experience in HSCT in pediatric SCT; Gaurav Kharya gave a very interesting talk on the use of PBSC (PTCY) in the Indian experience; Siana Nkya reported on the development of a SCD transplant program in Tansania. Furthermore, Lawrence Faulkner from Italy, well-known for his commitment in the Cure2Children Foundation, discussed the cure of severe hemoglobinopathies as an opportunity to expand global access to bone marrow transplantation. Finally, Carmen Bonfirm reported the Brazil experience of haploidentical HSCT using PTCY as GvHD prophylaxis. The socio-economical problems in low- and middle-income countries are relevant obstacles in providing the best cure for countries with a high prevalence of hemoglobinopathies, as well as the often-significant geographical distances between the place of residence and the transplant units.
In part 2 of the session, Kristin Page presented the CIBMTR data on HSCT in SCD, and Akif Yesilipek and Isabelle Thuret shared the experience of HSCT in thalassemia in Turkey and in France, respectively. In conclusion of this particularly interesting session, Miguel Abboud discussed the ethical and organizational challenges of SCD research in low and middle-income countries.
In the final Session on advances in transplant technology, Francoise Bernaudin (France) presented on the important topic of correction of vascular complications, and Sarita Jaiswal (India) discussed via video presentation the phenomenon of macrophage activation syndrome in the setting of haploidentical HSCT for HGB.
In conclusion, also this edition of the Haemoglobinopathies Meeting in Regensburg can be considered a very successful event, evidenced by the very well attended sessions, and by the extraordinarily constructive discussions with the audience, emphasizing the substantial relevance of new therapies for SCD and TDT, sharing both an absolute indication for a curative approach.
Nurses Group Programme
Summary written by Hilda Mekelenkamp, Nurses Group Paediatric Committee Chair and PDWP Nurse; Marjola Gjergji and Ida Ophorst-Bremer, Paediatric Committee Members; Trude Minnee, Speaker at the PDWP Educational Meeting; and Judith Timmermans, Paediatric Grant Winner.
We had a great meeting on haemoglobinopathies in Regensburg with an interesting parallel nurses track. Twenty-five nurses attended the meeting with the expectation to learn from each other and to discuss and exchange experiences. Nurses from eleven countries with experience in adult, pediatric, hematology and/or SCT, more or less experienced in HSCT nursing, participated actively in the sessions. Especially the easily accessible and enthusiastic way of discussing all topics together in this international context made this meeting a great success.
Session I (Part 1): Pre-transplant care
The first speaker of this session was Kelly Hennessy from UK. She talked about the “Supportive care in sickle cell disease” starting from introducing the sickle cell disease and going through numerous side effects, transfusion program, iron chelation drugs and outpatient’s support.
The second topic was the “Pain management in sickle cell disease”, explained by Regina Kulzer from Germany. Her talk was focused on how to manage the pain by medical and non-medical therapies like talk therapy and aromatherapy.
Third topic was performed by Lisbeth Andersson Lund from Sweden. She talked about the “Supportive care Thalassemia” bringing the experience from her center how they support and educate thalassemia patients through an educational program. She also explained the therapies used like exjade, desferal and ferripax and the side effects but also the importance of psychology and emotional support of thalassemia patients through specific activities.
The last talk was performed by Lawrence Faulkner from Italy/India who brought up an important issue like the “Infertility” as a crucial argument for all the Thalassemia patients who will undergo transplantation, involving all the attenders in free communication on the topic.
Session I (Part 2): Pre-transplant care
Hilda Mekelenkamp spoke about HSCT decision-making for hemoglobinopathy patients. She highlighted the importance of exploring patient’s preferences, needs, wishes and goals, taking time to discuss these preferences and the importance of including these while making an HSCT decision.
Sandrine Bremathas explained how patients are carefully prepared for HSCT. Several checklists support this preparation and included medical and psycho-social aspects.
Donor choice and donor care was discussed by Daphna Hutt. Choosing the best donor for our patients brings many considerations and a careful weighing of all these aspects.
Session II: Research session
Ida Ophorst-Bremer talked about ‘ Is there evidence to provide the best care’. She explained the definition of evidence-based nursing (EBN) and the three main principles: best research evidence, clinical expertise and patient’s perspectives and preferences. Ida guided us through the 5 steps of EBN and she illustrated this nicely with examples from her own practice.
Hilda Mekelenkamp explained how to write an abstract and why sharing your projects and/ or experiences is important. There are always several excuses for not writing an abstract, but each nurse can be proud of his/her work and it is worth presenting and discussing this with others.
During the last talk of this session Valentina Biagioli presented ‘how to present your research/project’. Valentina explained the importance of sharing your work, like passing on the benefits to others, to give an impact, to influence policy and to draw stakeholders’ attention. Different ways can be used like scientific/newspaper articles, books, presentations, posters, websites and educational sessions.
After these talks we continued with a nice group discussion, some of the attendees were experienced in presenting, where others were less experiences but very keen on doing this in the future. To support the integration of nursing research into our clinical practices, attendees responded that management commitment and time are important.
Session III: Clinical transplant care
Pain management during HSCT by Thaisa Zendath. An interesting talk which showed that the sensation of pain is different for every individual whereby biological (genes), psychological (coping skills, personality) and social factors (culture, religion) play a role. Doing a pain assessment at the start of the treatment is essential to find out the baseline and what could help for each individual patient.
Skin care during HSCT by Judith Timmermans. This presentation started with the introduction of a protocol with guidelines to give advice and care of the patient getting treosulfan/thiotepa. By frequently showering during and after treosulfan/thiotepa, no use of perfumed skin care products, skin problems decreased and less skin biopsies. More studies should be done to the treatment of pruritis (itchy skin). This is a common side effect, but options to relief the itch are not yet sufficient.
The special psychological & neurocognitive situation in SCD and B thalassemia patient by Elisabeth Kuhn-Wolff. Elisabeth showed us a neurocognitive assessment study before HSCT and one year after. The common intelligence was almost stable but it influenced the short-term memory and improved fine skills. The eye hand coordination worsened.
Nursing care in gene therapy by Matteo Amicucci. Matteo shared with us the gene therapy procedure. The history and rebirth of gene therapy in non-malignant diseases. He showed the clinical pathway and nursing and how to prepare and administer gene therapy in the “Italian” practice.
Case presentation gene therapy in Thalassemia by Caroline Aumeier & Ann Katrin Lang. This session was about a patient who got CRISP-CAS instead of a HSCT, because he was not suitable for HSCT. After aferese he got genetically modified bloodcells. In this case the patient had a diversity of side effects/complication like, skin problems, low platelets, mucositis, low oxygen.
Family perspectives on gene therapy for thalassemia (video) by Marjola Gjerjgi. An impressive story about a mother who was looking for therapy options for her two children after years of getting transfusion for their disease. Emanuele and Erica who did want a future without thalassemia. They managed to get gene therapy. They spoke about their anxiety and worries but happily it worked out very well for them and they have a “normal” live after gene therapy treatment.
Session IV: Post-transplant care
This session started with a video presentation from Julia Ruiz about the nurses’ role in late effects after a HSCT. Julia started with showing us data about the amount of transplantations and data about transplant indications. After this, Julia talked about the late effects after HSCT. There is a wide range of late effects with increased burden of serious chronic conditions and impairments involving organ systems and impacts on overall quality of life. Balance between cure-improvement and avoiding risk factors for late effects and toxicity is a challenge in transplant decision in hemoglobinopathies. The complexity of the late effects in HSCT survivors means that patients require life-long assessment guided by protocols. In conclusion, long term follow-up is an integral part of HSCT care, which ensures surveillance and intervention for early and late complications. It is important that long term follow-up consultation is coordinated and led by an nurse, integrated in a multidisciplinary team and to establish a patient-centered care pathway including a transition plan.
After this, Trude Minnee, gave a presentation about transition to adult care. She started with her take home message, which is that a nurse practitioner is a key player in the transition to adult care. She explained the late effects of a HSCT and why it is so important that there is a long-term follow-up. An important part about the long-term follow-up is that there is a good transition to adult care, so the follow-up continues. After this, she explained the core principles of good transition to adult care according to the Dutch guideline, which are patient centered care, teamwork, coordination and continuity of care, self-management and independence. It is important to start talking about the transition with patients that are 12-14 years old. And gradually give them more and more responsibility, so that they are ready for the transition to adult care.
This session was ended by a debate about communication challenges in pediatric nursing led by Hilda Mekelenkamp, Marjola Gjergji and Eugenia Trigoso. We started with the question ‘What makes nurses’ communication unique? Everybody agrees that nurses have a feeling for the needs of the patients and the family, ‘can read the patient’ and can adjust the communication to the level of the patient. After this there was a talk about the barriers in nurses’ communication. 41% of the group thinks that time is the biggest problem, followed by a language barrier. Then, there was a poll about using interpreters when facing language barriers. Every member of the session voted that they use an interpreter very often. Also, everybody agrees that in their hospital the services aligned with cultural differences, for example regarding diets/food habits.
Session V: Nursing Challenges
In the first session Eugenia Trigoso told us about the Global Education Concept (GEC) activities: ‘Reaching out globally through education’. In lower-and middle-income countries (MNIC) nurses faces challenges, including inadequate staffing, lack of support, limited access to education and unsafe practice environments. The success of a hematopoietic stem cell transplantation program relies on appropriately trained and experienced nursing staff. Therefore, the EBMT nursing group’s mission is to enhance and value the nurse’s role globally, supporting and sharing knowledge through communication, advocacy, research, training and education. They organize and coordinate HSCT nursing educational events and activities in MNIC. They work in collaboration with like-minded entities to foster and strengthen the ability of local nurse leaders to develop and sustain educational networks. And they creating a model not solely dependent on EBMT but that becomes part of the global community.
In the second session Eugenia Trigoso told us about the quality management in nursing. She told us all about the comprehensive quality management system ‘JACIE’ and how to apply them within the organization. The main principle in all this is teamwork. The staff-nurse (who is at the heart of the system) plays a vital role in de quality improvement of health care services. Inspectors are the backbone of JACIE, without them there is no accreditation process. Becoming an inspector is a wonderful way to contribute to maintaining global quality standards. Quality management inspectors and apheresis inspectors (nurses) are desperately needed!
In the third session Christoph Bauer & Tanja Kremer told us about the differences in nurses’ training in Europe. They have compared the nurses’ training in Germany with France, Switzerland, Austria and Great Britain. The nurses’ training is different in each country. Due to the new training in Germany, the trainees are used in fewer areas of pediatrics. The operating time in practice is significantly reduced. In order to compensate for this deficit, trained and comprehensive training is required in Germany in order to be able to adequately care for patients and families in pediatric hematology and oncology. There is a training after the three years of apprentices, for 6 months. Training by a qualified practical instruction for nursing one by one. In this time the instructor can change to prevent from unilateral and depending on one person. They also aid a tool: specialized guidelines for pediatric oncologic wards with stem cell transplantation.
An interesting discussion started.
In the last session there was time to debate ethical issues. First, we heard about the norms and values and how they influence our moral values in healthcare. We also learned how a moral value can become a moral conflict. An interesting ethical issue and discussion started based on a case presented by one of the attendees.