18-20 September 2025, Roma, Italy
Summary report written by Syed Ali (Australia), Giorgia Ranucci (Italy) and Daniele Sannipoli (Italy).
From September 18th to 20th, Rome hosted this inspiring joint Meeting organised by the EBMT Working Parties on Chronic Malignancies (CMWP) and Autoimmune Diseases (ADWP). With precious contributions from local organisers Carmelo Gurnari and Raffaella Greco, the event was overseen by Donald McLornan (CMWP Chair), Tobias Alexander (ADWP Chair), Joanna Drozd-Sokolowska (CMWP Co-Secretary), Kavita Raj (CMWP Co-Secretary), and Elisa Roldan-Galvan (ADWP Secretary).
Session I, chaired by Tobias Alexander and Donald McLornan, focused on current EBMT guidelines and recommendations on hematopoietic stem cell transplantation (HCT) in myelodysplastic syndromes (MDS) and HCT and CAR-T in autoimmune diseases (ADs). Carmelo Gurnari reviewed the latest EBMT indications for HCT in MDS, emphasizing the integration of disease-specific and transplant-related risk factors to predict outcomes in patients undergoing the procedure. He discussed the management of high-risk MDS patients—classified as such according to the IPSS-M—who require immediate transplantation. Furthermore, he detailed the stratification of specific MDS subgroups, including TP53-mutated, del(5q), and germline-mutated cases, and showed algorithms to better identify which lower-risk patients might benefit eventually from HCT. Donor selection and conditioning regimens tailored for these subpopulations were also discussed, alongside the importance of post-transplant MRD assessment and potential therapeutic strategies in MRD-positive patients. The focus then shifted to ADs, with Elisa Roldan-Galvan explaining the rationale for HCT in these conditions: a single, intensive intervention aimed at immune reconstitution and eradication of autoreactive immune cells, with the goal of achieving minimal toxicity and durable, drug-free remission. She reviewed data on the number of procedures performed, safety, efficacy, conditioning regimens, and current indications, particularly in multiple sclerosis (MS), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE). The necessity of multidisciplinary collaboration was underscored for optimal outcomes. Raffaella Greco concluded the session by discussing recent recommendations on CAR-T cell therapies in autoimmune diseases. She highlighted the advantages of CAR-T approaches, such as tissue penetration, co-targeting of plasmablasts, and durability. She reviewed existing protocols, emphasizing considerations for patient eligibility (including viral status assessment), timing of leukapheresis, washout periods, supportive care, and follow-up. An update on the 2023 Harmonization Project within ADWP further contextualized these strategies.
Session II, chaired by Kavita Raj and Carmelo Gurnari, addressed diagnostic and prognostic issues in MDS. Mario Cazzola examined the impact of the molecular era on MDS, emphasizing the importance of re-evaluating survival benefits conferred by treatment based on disease biology, especially in high-risk (HR) cases. Nico Gagelmann provided a detailed analysis of clinical determinants guiding the decision to perform HCT, focusing on prognostic scoring systems, fitness and comorbidity assessments, and the role of genetic profiling in decision-making. Coming from the experience of AIPSSmol-MF, Adrian Mosquera presented data validating the predictive value of AIPSS-MDS for overall survival (OS) and leukemia-free survival (LFS), based also on Latin American clinical experiences.
With the guidance of chairs Fernando Barroso Duarte and Nicolaus Kröger, the Session III advanced to therapeutic strategies for MDS. Maria Teresa Voso discussed treatment algorithms for lower-risk MDS, including response prediction to erythropoiesis-stimulating agents (ESAs), response optimization, and outcomes from the phase III COMMANDS trial comparing Luspatercept vs Erythropoietin. The development of the prognostic score IPSS-del(5q) for leukemia-free survival (LFS) was also presented. The session concluded with an overview of ongoing clinical trials testing novel agents such as Imetelstat and Eltrombopag. The focus then shifted to high-risk MDS treatment strategies, led by Amer Zeidan, who examined the long-coursed hypomethylating agents (HMAs) in monotherapy and related controversies. The discussion emphasized the importance of integrating genomic, biological, and phenotypic data to refine response assessment. The potential validation of the IWG-20/23 response criteria was discussed, alongside promising combination therapies (e.g., STIMULUS-MDS trials with Sabatolimab + AZA, AK-117 or Ligufalimab + AZA, Bexmarilimab as novel anti-Clever-1 IgG4 antibody, and Venetoclax-based regimens as in the VERONA study). Jaroslaw Maciejewski provided a translational perspective, shifting the focus from clinical to laboratory point of view. He examined MDS/AML through molecular clustering and progression patterns, emphasizing the necessity of integrating molecular nosology to improve prediction of drug responsiveness, particularly in relapsed/refractory (R/R) cases. He highlighted the potential of in vitro sensitivity testing and advanced genotypic/pheno-typic clustering approaches, such as machine learning algorithms, to better stratify patients and tailor therapies. Gonzalo Bentolila explored the situation in Latin America regarding genomics, treatment options, and access to allo-HCT for MDS patients. He discussed how economic policies and healthcare strategies influence equitable access to advanced therapies and transplantation across the area. The session concluded with a compelling case presentation by Giuliano Filippini Velazquez, outlining the management of a patient with secondary AML (s-AML). The patient underwent a successful second allo-HCT from an haploidentical donor receiving dose-reduced post-transplant cyclophosphamide (PTCy) to treat MDS relapse. The patient resulted refractory to hypomethylating agents (HMA) and donor lymphocyte infusions (DLI), underscoring the complexities and evolving strategies in managing refractory MDS/AML.
Session IV, chaired by Joanna Drozd-Sokolowska and Anna Paola Iori, concluded the first day of the meeting with discussions on autoinflammation in hematology and beyond. Carmelo Gurnari introduced the VEXAS syndrome, providing an overview of its clinical hematological presentation and highlighting recent advances, particularly regarding UBA1 clonal dynamics and potential therapeutic considerations. He also shared insights from data obtained through the AIDA Network. Promising developments were presented concerning the PAXIS protocol, a Phase II study evaluating the efficacy and safety of Pacritinib in patients with VEXAS. Francesco Onida explored the close relationship between chronic myelomonocytic leukemia (CMML) and ADs. He reviewed pertinent literature and discussed the possible genomic landscape underlying this spectrum. Coralie Bloch offered new insights into hemophagocytic lymphohistiocytosis (HLH), focusing especially on defects in lymphocyte cytotoxic function. She presented cytokine profiling data from the French cohort and discussed the potential role of IL-10 in the disease pathophysiology and the mechanism of action of Itacitinib, a novel anti-JAK agent. Sarah Leone shared a remarkable clinical case involving an unusual brisk CAR-T cell expansion following ciltacabtagene autoleucel infusion in a multiple myeloma patient. The case was complicated by neurological symptoms, polymicrobial infections, and most notably, an immune effector-cell-associated HLH-like syndrome. Syed Ali concluded the session by presenting clinical data and a meta-analysis regarding hematopoietic cell transplantation (HCT) in VEXAS syndrome, emphasizing current experiences and future perspectives.
Day two opened with the Joint Physician–Nurse Session focusing on the contemporary approach to HCT in MDS. The session was chaired by Dr. Maaike de Ruijter (NL) and Dr. William Arcese (IT). Talks addressed donor selection, pre-transplant strategies, conditioning intensity, and post-transplant maintenance.
The opening lecture by Dr. Kavita Raj examined how post-transplant cyclophosphamide (PTCy) has reshaped donor choice, expanding access to haploidentical and mismatched unrelated transplantation. While overall survival is broadly comparable among matched sibling, fully matched unrelated (MUD) and haploidentical donors under PTCy in many disease settings, notable differences remain in MDS. Younger MUD donors tend to outperform haploidentical donors in reduced-intensity conditioning settings. Dr. Raj also proposed a donor-selection algorithm integrating donor age, HLA matching, CMV status and graft source.
The next speaker, Dr. Nicolaus Kröger, weighed the pros and cons of bridging therapy before transplant. Bridging may decrease disease burden and stabilise patients awaiting a donor but can also increase non-relapse mortality and select for refractory disease. Analyses from EBMT and French cohorts suggest that outcomes are best for patients in complete remission at transplant; azacitidine bridging has not consistently improved results. Better predictive tools are needed to identify which patients truly benefit.
Turning to conditioning, Dr. Joanna Drozd-Sokolowska reviewed the evolution from myeloablative (MAC) to reduced-intensity (RIC) conditioning. Data from randomised and prospective trials show no long-term survival benefit for RIC in MDS, with a trend toward higher relapse risk compared with MAC. EBMT survey data indicate no strict age limit for MAC, and machine-learning tools to match regimen intensity to individual risk—especially for MRD-positive patients—are emerging.
Concluding the MDS session, Dr. Marie Robin stressed the grim prognosis after post-transplant relapse in MDS (median OS 4–5 months). Maintenance strategies—azacitidine, decitabine (including oral), venetoclax combinations and donor lymphocyte infusions—show promise but also high discontinuation rates and no established MRD-guided standard. Several phase 3 trials (VIALE-T, AMADEUS) are awaited. She underscored the importance of shared decision-making with patients and the need to balance infection risk with relapse prevention.
Session V covered HCT in autoinflammation and autoimmunity by five presenters and was chaired by John Snowden and Andrea Bacigalupo.
Donal McLornan highlighted high morbidity of VEXAS and a five-year survival between 15 to 80%. As patients required between 4 to 5 treatments, and had impaired quality of life, HCT as a treatment option was raised with patient centred focus in mind. HCT offers curative intent with eradication of UBA1 clone, however given only very few reported cases, there is a need for globally accepted risk stratification tools such as those with progressive marrow failure, transfusion dependency, treatment refractory hyperinflammation.
Mathieu Puyade discussed that HCT in Bechet’s is seldomly reported, and as the disease can be severe with life threatening aneurysms, thromboembolic events and gastrointestinal perforation and/or fistula this treatment entity could be considered in selected patients. One specific patient group raised was those with myelodysplasia and trisomy 8 who have rare association with Bechet’s
Nicoletta del Papa then showed that HCT in Systemic sclerosis is the only disease modifiable treatment, unlike immunosuppressive and anti-fibrotic therapies. While HCT had a better survival rate over a 60-month follow up, up to 30% of patients still relapsed with disease raised possibly due to cessation of mycophenolate pre-transplant. Rituximab as a temporising measure pre-transplant was also raised as an important consideration.
Fernando Barroso Duarte discussed HCT in autoimmune disease in Brazil with dataset from a registry of 46 patients mostly peripheral blood, autologous type and overall survival of 95% at two years.
Gavin Brittain showed early data on a study evaluating the role of RNA signatures in a small pilot study evaluating patients with multiple sclerosis and showed repopulation of both B- and T cells following HCT.
Session VI covered plasma cells as treatment targets in haematology and autoimmune diseases by six presenters, was chaired by Patrizia Chiusolo and Paolo Muraro.
Elisa Roldan Galvin outlined novel treatments in multiple myeloma including daratumumab, bispecifics (BCMA + GPRC5D) and trispecifics (BCMA, CD28 and CD3). Results from the CARTITUDE-1 were presented with a progression free survival of over 5 years, and importantly without requiring maintenance therapy.
Patrick Hayden further discussed bispecifics in MM, including concepts of holding therapy (goal control disease without jeopardising feasibility of CAR T therapy) and bridging therapy (avoid clinical deterioration and reduce disease burden). In the latter, specific patient considerations which impact selection of bridging therapy were also discussed. For example, t(11:14) and consideration of venetoclax, and anorexia/failure to thrive and consider a BCMA bispecific as opposed to talquetamab or Selinexor which may be associated with increased risk of toxicities.
Frazin Mashreghi highlighted differential plasma cell populations in patients with SLE and transplantation through single cell sequencing.
Tobias Alexander presented the utility of teclistamab in achieving complete remission in SLE and particularly highlighted the target at the bone marrow.
Paulina Piesik presented two neurological autoimmune disease case presentations in whom disease flared post-transplant and daratumumab was trialled. The patient with IgLON5 disease responded favourably, while the other patient with MOG1 did not respond to this treatment.
Jonathan Wickel presented a case of IgM paraprotein associated neuropathy in whom teclistamab was trialled given no responses to IVIG, PLEX, steroids or immunoadsorption. The patient showed favourable response with grade two CRS treated with tocilizumab, IVIG for hypogammaglobulinaemia and neutropaenia for which short course of GCSF was given.
Session VII covered novel cellular therapies in autoimmune diseases with five presenters and was chaired by Siona Sica and Dominique Farge.
Ricardo Grieschaber-Bouyer presented data on bispecific blinatumomab for rheumatoid arthritis showing robust depletion of B cells in both tissues and peripheral blood, but not lymph nodes. Favourable clinical response was observed over a 12-week period. In another patient, blinatumomab was ineffective, and response teclistamab was observed.
Doron Rimar presented summary of CAR T cell therapy in rheumatoid arthritis, including recommendation for its use in the Persistent Inflammatory Refractory Rheumatoid Arthritis (PIRRA) subtype.
Marco Becilli showed local experience of CAR T cell therapy in a paediatric context in five patients: two with SLE and three with JDM. Both CRS and ICANS were reported but resolved spontaneously. There was one infection (pulmonary aspergillosis) reported. Major favourable responses were seen in both patients with SLE and two of the three patients with JDM.
Richard Burt demonstrated poor efficacy of treatments to date regarding ALS, and some very early data suggests extracellular vesicles delivery might promote tissue regeneration.
Ioanna Minopoulou highlighted a patient with rapid clinical improvement for seropositive rheumatoid arthritis following autologous CD19 CAR T. There was no toxicity and was associated with decline in circulating CCP antibodies. They also highlighted phase two trial which will recruit patients comparing rituximab to this CAR T treatment.
Day three opened with the Joint Nurse–Physician Session focusing on HSCT and Cellular Therapies for Autoimmune Neurologic Diseases. This session, chaired by Dr. Claudia Boglione (IT) and Dr. Basil Sharrack (UK), highlighted the growing role of HSCT and cellular therapies in treating autoimmune neurologic diseases, presenting data from multiple sclerosis to emerging CAR-T approaches.
In the first talk, Dr. Alice Mariottini presented data on autologous HSCT in multiple sclerosis, highlighting effects on T and B cells, reduction of oligoclonal bands and improved immune repertoire. She reviewed clinical monitoring (MRI, EDSS, NEDA) and noted that while HSCT appears superior to high-efficacy DMTs in controlling relapses, its effect on disability progression is heterogeneous. Because current transplant-related mortality is near zero and axonal/fibrotic damage is not reversed by HSCT, earlier use of auto-HCT in aggressive disease may be warranted.
Moving to CAR-T in MS, Dr. Lena Kristina Pfeffer discussed the first pilot experience of anti-CD19 CAR-T in MS (five patients with RRMS/SPMS/PPMS). Four showed CAR-T expansion with manageable CRS but no clear EDSS improvement and MRI effects that were difficult to interpret (LICAT versus PD). She highlighted the need for larger mechanistic studies to clarify targets, timing and long-term immune modulation.
Expanding the landscape of HSCT and CAR-T in autoimmune disease, Dr. Tobias Hegelmaier presented illustrative CAR-T cases in refractory myasthenia gravis and autoimmune encephalitis, suggesting rapid symptom improvement and B-cell depletion. Over 30 phase I–II trials are ongoing in neurology. Open questions include optimal lymphodepletion, cell type (autologous vs allogeneic) and long-term safety.
Poster session
Moderated by Donal McLornan and Tobias Alexander, the session featured flash-slide presentations from poster authors on a wide range of topics.
Dr. Hannah Young presented her work on the need to provide adequate patient information for individuals with MS considering or undergoing autologous HSCT, aiming to foster a more patient-centred approach.
Shifting to preclinical data, Dr. Madalina Nistor showed experimental proof of efficacy for an academic anti-ROR1 CAR-T product enriched with the iCasp9 suicide gene in mantle cell lymphoma, using both in vitro and in vivo (mouse) models.
Returning to clinical research, Dr. Ambra Fumagalli analysed the impact of the CARE-BMT cardiovascular risk score in multiple myeloma patients undergoing autologous HSCT.
Dr. Giorgia Ranucci then presented data from the Italian VEXAS network, highlighting the frequency of thrombotic events in this autoinflammatory condition and discussing associated treatment strategies.
Next, Dr. Lugain Abdalla reported on a challenging case of systemic mastocytosis associated with high-risk MDS treated with multiple therapies (including avapritinib), which resulted in poor graft function after alloHSCT.
Dr. Maria Chiara Quattrocchi focused on the severe infectious risks associated with prolonged bispecific antibody therapy in multiple myeloma.
Finally, Dr. Daniele Sannipoli compared the classical MTSS score with a machine-learning–based “Allo Risk Stratifier” model in patients with myelofibrosis, aiming to improve prediction of early post-HSCT mortality.
Session VIII covered immune monitoring post CAR T therapy and late complications for autoimmune disease by four presenters and was chaired by Franco Locatelli and Raffaella Greco.
Simona Pagliuca covered immune monitoring post CAR T and highlighted the need to predict efficacy, anticipate toxicity, manage infections and understand immune reconstitution. Standard and multiparametric flow cytometry and to a lesser extend polymerase chain reaction are available clinically, while the remainder are limited in the research setting (e.g., single cell RNAseq, TCR repertoire, multimodal integrated characterisation, single cell transcriptomics, epigenomics and metabolomics).
Kirill Krigizov presented on the late complications of HCT and highlighted the importance of routine screening, monitoring, and prompt treatment initiation. The importance of secondary autoimmunity, either de-novo or within the spectrum of the original autoimmune disease was also shown.
Maeve O’Reilly presented a summary on the late CAR T cell therapy complications and showed that data in its management for autoimmune is limited given it was only initiated some four years prior when compared to treatment in haematological malignancies which is approximately 10 to 5years). Infection was the chief cause of non-relapse mortality (50%) and importance of prophylaxis and vaccination was presented. Additional complications such as late cytopaenia and therapy related myeloid neoplasms were also shown.
Matteo Doglio presented data on secondary HLH post CAR T therapy showing incidence of approximately 3.6% at 90 days, and that most important factor was history of B ALL at odds ratio of 7.7 compared to B cell lymphomas at odds ratio of 2.0. Clinically fever most common (though not 100%), followed by liver, renal and lung toxicity respectively. Most patients (80%) recovered, however at two years around 40% had their haematological disease relapse. The role of emapalumab and CXCL9 was also briefly discussed in the question-and-answer session.