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76Cellular Therapy and Transplantation (CTT). Vol. 12, No. 2, 2023 doi: 10.18620/ctt-1866-8836-2023-12-2-57-68 Submitted: 01 June 2023, accepted: 23 June 2023
I EBMT-2023: overview in brief
Andrey M. Chekalov, Liubov' A. Tsvetkova, Nikita V. Levkovskyi, Tatiana A. Rudakova, Maxim A. Kucher, Alexander A. Siniaev, Alexander D. Kulagin
RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia
Dr. Andrey M. Chekalov, RM Gorbacheva Research Institute Phone: +7 (981) 910-15-09
of Pediatric Oncology, Hematology and Transplantology, E-mail: a.m.chekalov@gmail.com.
Pavlov University, 6-8 L. Tolstoy St, 197022, St. Petersburg, Russia
Citation: Chekalov AM, Tsvetkova LA, Levkovskyi NV, et al. EBMT-2023: Overview in brief. Cell Ther Transplant 2023; 12(2): 57-68.
Summary
The article contains a short overview of reports and poster communications which have drawn special interest of Russian participants from the St. Petersburg Pavlov University at the recent Annual EBMT Meeting. It represents a collective view of R. Gorbacheva Memorial Institute of Pediatric Oncology, Hematology and Transplantation (CIC 725) on some current trends in hematopoietic stem cell transplantation including treatment of leukemias, lymphomas, myelodysplastic syndrome, non-malignant blood disorders, both in pediatric and adult clinical settings.
Keywords
Hematopoietic stem cell transplantation, EBMT-2023 Meeting, overview.
Introduction
This year, 49th Annual Meeting of the EBMT proceeded in Paris, France, in hybrid format. This remarkable event was attended by 2700 specialists in hematopoietic stem cell transplantation and adjacent areas of hematology and cell therapy from all European countries, as well as USA, China, UK, Israel, Russia and other states. The scientific program included 655 presentations, over 1100 poster communications.
A total of 32 awards were granted during this year's Annual Meeting. All winners are available on the EBMT Website. Generally, the Russian specialists actively participated at various clinical and scientific sessions, and several reports were awarded by the EBMT Coordination Committee. In particular, a Springer award was entitled to a team from the R. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University (St. Petersburg, Russia).
This overview is presented by Russian participants at this Meeting and concerns a number of reports (both lectures
and poster communications) which proved to be interesting to the young specialists who were honored to visit appropriate scientific sessions at the 49th EBMT Congress.
Appropriate titles and authors names are provided as listed in scientific program. Some pertinent research articles are also referred. The Abstract Book of the EBMT Meeting will be in Open Access in the summer 2023.
Acute leukemia
At Acute Leukaemia Working Party (ALPW) Session, Dr. Jordi Esteve demostrated new insights and changes of WHO classification and International Consensus Classification (ICC) of acute myeloid leukemia (AML), aiming to include all genetically recognized classes of AML including rare subtypes [1]. Molecular diagnostics of myelodysplasia-as-sociated AML is now based on genetic mutations and characteristic cytogenetic abnormalities. The AML cases with TP53 mutations define a separate clinical entity. The main issues of using the new classifications include a need for the Next-Generation DNA Sequencing (NGS) as well as absence
of consensus between the two main classifications. The minimal blast count has not yet been established in the AML diagnosis.
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only treatment with the potential to cure AML. However, there is no unified approach to the treatment of the post-transplant relapses. A second allo-HSCT (HCT2) and donor lymphocyte infusions (DLI) are potentially effective treatment options. Retrospective registry study from the ALPW EBMT involving 418 adults who received an allo-HCT2 (n=137) or DLI (n=281) for post-allograft-relapsed AML There was no apparent difference in overall survival (OS), whether an allo-HCT2 or DLI was prescribed. OS was better if either of these procedures was offered when the patient was in complete remission. Conversely it was lower for patients relapsing within less than 6 months after an allo-HCTl. However, the HLAloss Collaborative Study demonstrates that 22.6% of relapses after haploidentical HSCT, 11.9% after MMUD HSCT, 4.3% after 10/10 MUD HSCT have shown a genomic loss of an HLA haplotype encoding incompatible alleles ("HLA loss"), whereby leukemic cells evade the graft-versus-leukemia effect. Prof. MA Khar-fan-Dabaja in his report, based on these data and the results of a systematic review proposed a therapy algorithm for the cases of relapse after allo-HCT in and absence of "HLA loss", i.e., possible usage of both DLI and allo-HCT2. In case of recurrence with "HLA loss", it is worth considering allo-HCT from different donor [2].
Lymphoma
As part of the Lymphoma Working Party (LWP) session and GOCART ongoing projects, Prof. Bertram Glass demonstrated the results of the EBMT database comparing allo-HSCT and CAR-T therapy in patients with r/r large B cell lymphoma [3]. The analysis included 515 patients (212-allo-HSCT, 303-CAR-T) in >3rd line of therapy with known International Prognostic Index.
(IPI) and LDH levels before starting cell therapy. In general, CAR-T therapy showed a significant advantage in terms of Overall survival (OS). Upon a multivariate analysis, depending on the risk group according to IPI. In low-IPI cases, CAR-T had a positive effect on OS (p<0.0001) and leukemia-free survival (LFS) (p=0.00145). Non-relapse mortality (NRM) in both low and high IPI cases was sufficiently reduced following CAR-T therapy (p>0.00001). Survival analysis showed that CAR-T significantly improved 12-month OS and Progression-free survival (PFS) in the low/low intermediate IPI group. However, but no benefit of CAR-T versus allo-HSCT was found in the high/high intermediate IPI group.
Prof. Bertram Glass has also demonstrated the results from EBMT database concerning efficacy and toxicity of CD19-targeted CAR-T cell in the treatment of r/r primary and secondary CNS lymphoma. The analysis included 74 patients with median age of 61.6 years. The majority (64.9%) of patients received CAR-T in > 3rd line of therapy. The 12-mo OS and PFS rates were 51.1% [95% CI 40.2-64.8] and 33.7% [95% CI 24.3-46.7], respectively [4].
Results of propensity score-matched controlled prospective trial of allo-HSCT in advanced cutaneous T-cell lymphomas were reported by Adele de Masson. The study included 99 patients from 17 medical centers in France (55, HSCT group; 44, non-HSCT group). The 3-year PFS in the intent-to-treat (ITT) analysis was higher in the HSCT group [HR-0.38 (0.21-0.69), p<0.0001]; however, difference in OS was not significant. With the development of relapse, most patients in the HSCT group achieved a response to therapy, while those in the non-HSCT group had progression of the disease or died [5].
Myelofibrosis
A number of lectures were devoted to management of myeloproliferative neoplasms at a special session held by Chronic Malignancies Working Party (CMWP) e.g., they highlighted controversies in application of allo-HSCT for myelofibrosis (MF). Development and use of modern scoring systems might result in more accurate risk stratification and promising results of allo-HSCT. In particular, new molecular data should be used for selecting patients for allo-HSCT with poor prognosis associated with high-risk mutations, e.g., multi-hit TP53 and RAS pathway mutations. Combination of molecular, clinical and transplant-specific information is reflected in Myelofibrosis Transplant Scoring System (MTSS) as well as DPSS/-Plus, MIPSS70 v2.0 for primary MF and MYSEC-PM for secondary MF should be considered when making decision about allo-HSCT [6].
The choice of the ideal conditioning regimen for MF patients is also limited. Myeloablative conditioning (MAC) do not improve outcomes in high-risk group. RIC regimens should be considered for patients older than 50 years old or with poor performance status or comorbidities. The data suggest a combination of fludarabine and busulfan to become the standard conditioning regimen in MF patients for both MAC and RIC protocols [7, 8].
General trends for allo-HSCT in MF are as follows: matched related donor, preference of peripheral blood stem cells over bone marrow as a source of transplant, and higher doses of CD34+ (>7x106/kg) [9].
GvHD prophylaxis should follow the standard local institutional procedures. When transplanting from matched unrelated donors, ATG is commonly used to reduce aGH-VD in cases of matched related donors. Post-transplant cyclophosphamide (PTCy) is recommended in cases of HLA mismatch, a reduced PTCy dosage in HLA-matched or 9/10 related/URD might be of benefit. Peri- and post-transplant use of ruxolitinib show promising results by reducing aGvHD rates and higher OS [7].
Optimal management of splenomegaly was discussed during CMWP meeting. Splenomegaly is a sufficient factor in MF patients that affects engraftment and allo-HSCT outcomes. Pretransplant treatment with ruxolitinib, fedratinib may show good results. In cases of JAK inhibitor failure, one may use other JAK inhibitors, splenectomy or radiotherapy. A position paper by Polverelli et al. was offered on behalf of CMWP proposing the algorithm of splenomegaly management. Pretransplant targeted treatment of myelofibrosis and
essential thrombocytemia with calreticuline mutations or isocitrate dehydrogenase gene (IDH) inhibition (enasidenib, naviroclax) should be investigated as potentially optimizing therapies [10, 11].
Poor graft function and graft failure is another challenge in the MF setting. Thus, the second HSCT might be an option in this case. There is no supporting data for the choice of a different over original donor for the second HSCT [8].
The data evaluating a prognostic impact of high-risk mutations after allo-HSCT were presented by M.C. Finazzi (Bologna). Although the study did not show any differences in OS, non-relapse mortality and relapse rates in groups with and without high-risk mutations, NGS analysis and digital droplet PCR might be promising diagnostic options in monitoring MRD after allo-HSCT and could lead to better management of MF treatment post-transplant. [12, 13, 14].
Impact of comorbidities and body mass index was considered by N. Polverelli who presented an international analysis on behalf of the CMWP of EBMT. A large cohort study of MF patients submitted to allo-HSCT showed that over 50% of the patients had, at least, one comorbidity with, mostly, pulmonary disorders and revealed the prognostic role of Hematopoietic Cell Transplantation-specific Comorbidity Index (HSCT-CI), as well as lower BMI, upon the posttrans-plant NRM and OS rates [15].
New treatment modalities for myelofibrosis should target underlying pathophysiology of the disease: bone marrow niche modification, molecular pathways, inflammation mechanisms. Therefore, a combination of ruxolitinib with peg-IFN alfa, pelabresib, navitoclax or imetelstat might be a beneficial approach [6, 16, 17].
Myelodysplastic syndrome
The patients with myelodysplastic syndrome (MDS) are known to benefit from allo-HSCT, but timing of the transplantation is important. Analysis by Cutler et al in 2004 showed that patients with high-risk MDS should be transplanted immediately [18]. Current strategies aim at improving outcome in high-risk patients and reduce the number of patients failing to be transplanted, since, according to the Swedish registry, 24% of candidates could not receive transplant due to disease progression or poor somatic status or lack of donor [19].
Role of upfront allo-HSCT in MDS (especially with excess of blasts) was discussed, e.g., a German study which showed no differences in relapse-free survival between the patients who underwent upfront allo-HSCT and post-hypomethylat-ing agents, or patients subjected to intensive chemotherapy. Recent analysis suggested that treosulfan might improve the results of allo-HSCT compared with busulfan. Post-transplant treatment is still under investigation, as there are a few Phase II studies, i.e., eprenetapopt combined with 5-azacyt-idine shows promising results. At the same time, a maintenance monotherapy with 5-azacytidine gave no advantage in post-transplant period. Prophylactic donor lymphocytes infusion may reduce the risk of relapse by promoting graft-ver-sus-leukemia effect [20].
Results of retrospective study on behalf of CMWP of the EBMT were presented by Alicia Rovo [21]. Outcomes of CMML patients undergoing allo-HSCT were compared to MDS patients, aiming to identify and compare the factors associated with outcomes in both diseases. The study revealed significantly worse OS, PFS and relapse rate in CMML versus MDS, with no difference in NRM showing comparable outcomes of allo-HSCT in CMML and MDS patients. The worse survival in CMML appeared to be due to high rates of relapse after allo-HSCT, and advanced age was associated with more disappointing results in both diseases [22, 23].
CIBMTR analysis of mutational landscape in CMML showed that TP53 and DNMT3A mutations were associated with the worse OS and higher NRM rates after allo-HSCT [22]. Moreover, endothelial activation and stress index (EASIX) score were independent predictors of NRM in CMML patients Thus, integration of genetic and clinical characteristics might help to select candidates for allo-HSCT after entire and comprehensive evaluation of a patient eligibility and NRM risk estimation post-transplant [23, 24].
Recent studies show that clonal evolution independently and adversely impacts disease-free survival in patients with AML/MDS transformation and MF [26]. At the same time, clonal exposure to cytoreductive therapy differentially shapes clonal evolution in myeloproliferative neoplasms hTP53 mutations were selected in patients treated with hy-droxycarbamide and DNMT3A mutations in the IFN group.
Due to beneficial transplant-free treatment of chronic myeloid leukemia (CML), there was a lack of lectures on this topic. Nevertheless, Dr. Vlasova showed promising results of asciminib as a bridge therapy before allo-HSCT for CML [25].
HSCT in non-malignant disorders
The session was focused on hemoglobinopathies: sickle cell disease (SCD) and thalassemia. The proposed idea was that, in developed countries with conventional care, the SCD has become a systemic vasculopathy [26]. There are a number of diagnostic and treatment options for SCD such as early identification, prevention and screening, disease-modifing therapy which offers promising improvement of short-term parameters by means of new drugs like voxelotor, l-glutamine, crizanilizumab, as well as curative therapy like allo-HSCT, gene therapy and gene editing [27, 28, 29].Treatment of acute complications also plays in important role in SCD management. Effectiveness of the novel drugs is promising regarding reduction of hemolysis and vaso-occlusive crises, control of anemia. Nevertheless, due to the costly treatment and unknown long-term impact, this approach is not a panacea. A recent publication by Cronin et al demonstrates clinical outcomes of contemporary cohort of children and adults with SCD who received different treatment options, and allo-HSCT turned out to be the most promising [30].
Reversibility of SCD-related organ damage is another important issue, and studies show such an opportunity after allo-HSCT. However, primary and secondary graft failure remain an important complication after allo-HSCT, both in
SCD and beta thalassemia. Haploidentical HSCT with PT-Cy of alfa/beta T-cell depletion show promising results [31].
Novel treatment being available for both SCD and beta thal-assemia is Exa-cel which is produced by the ex vivo non-viral editing of erythroid-specific enhancer region of BCL11A in CD34+HSPCs and reduces erythroid specific expression of BCL11A thus resulting into increase of HbF levels and reducing veno-occlusive crises. Another promising option for beta-thalassemia therapy is betibeglogene autotemcel, a product of patient autologous cells transduced with a lentivi-ral vector what expresses the beta-globin gene [32].
Aplastic anemia (AA) and paroxysmal nocturnal hemoglobiuria (PNH)
Severe Aplastic Anemia Working Party presented a report on SARS-Cov-2 pandemic in setting of AA and PNH which demonstrated efficacy and safety of vaccine prophylaxis [33].
Haploidentical HSCT seem to be an encouraging option as the second-line therapy for AA or AA/PNH. However, haplo-HSCT as the first line in SAA needs development of optimal GvHD prophylaxis. Dr S. Giardino presented a retrospective analysis of haplo-HSCT in children with inherited bone marrow failure syndromes demonstrating that graft failure and infections remain the main issues in this setting, and TCR alfa/beta depletion platform might be a promising option for this category of patients [34].
Results of RACE study (A. Kolasekararaj, UK) have shown that mutations in AA are very common at diagnosis, a large number of variant alleles are present at low frequency, the mutations correlate with age, severe AA and higher absolute neutrophil count, and the mutational pattern is increasing during the time after treatment, irrespectively of type of therapy or response. No associations were shown between mutations at baseline and clinical response, overall survival or transformation to myeloproliferative neoplasm, as well as no impact of Eltrombopag was found upon mutations in upfront setting. The presence of non-PIGA/BCOR1/L1 mutations might be associated with increased risk of clonal evolution, especially with RUNX1, splicing factors ASXL1 [35].
Posttransplant non-infectious complications
Veno-occlusive disease
The data suggest that hepatic venoocclusive disease (VOD) with multiorgan failure is a widely underreported cause or death in post-transplant setting, and hepatic VOD is often misdiagnosed. Differential diagnosis of VOD can be challenging. Late onset of hepatic VOD with multiorgan disfunction proves to be not a rare condition which might be overlooked, as well as cases of VOD after autologous HSCT and hepatic VOD after RIC regimens [36, 37, 38]. Nowadays there exist tools to access the pre-transplant risk of VOD, i. e. EBMT VOD risk factors, King College Hospital criteria etc. [39]. The EBMT severity grading criteria may help with rapid VOD diagnosis in adults thus allowing earlier treatment, the EBMT severity grading application is available [40].
The latest update of DEFIFrance study analysis demonstrated better survival in severe versus very severe hepatic VOD as well as better outcomes for patients with anicteric course of VOD, and showed some benefits of defibrotide usage for the treatment of severe hepatic VOD post-HSCT [41]. Liver stiffness measurement might be used as a successful tool to diagnose VOD more precisely. EBMT adult diagnostic criteria are under revision and the paper is pending publication in BMT. Close monitoring is crucial for the timely diagnostic and start of the treatment [42].
HSCT-associated trombotic microangiopathy
Over the past two decades, HSCT associated trombotic mi-croangiopathy (HSCT-TMA) has been reported in up to 39% of pediatric and 68% of adult HSCT recipients, thus requiring specification of similar terms and criteria. At the same time there are differences in TMA presentation between pediatric and adult patients. Recently published consensus aims to harmonize definitions, but specific diagnostic and prognostic biomarkers still need validation [43, 44]. The drugs which target complement demonstrated potential in HSCT-TMA treatment but there are still no approved therapies. Blocking the lectin pathway of complement and coagulation cascade by narsoplimab is one of the novel approaches which are under investigation [45].
Complications of CAR T cell therapy
Early side effects of this treatment mode, such as cytokine release syndrome, immune effector cell-associated neuro-toxicity syndrome (ICANS), hemophagocytic lymphohisti-ocytosis (HLH), macrophage activation syndrome (MAS), cytopenias, infections are known CAR-T therapy complications, and methods of their management are under development. At the same time, late effects are still been investigated. Among novel strategies, anakinra, an interleukin-1 receptor antagonist, was effective for CRS/ICANS. Extra-corporeal cytokine removal showed efficacy for refractory cytokine-release syndrome (CRS). A randomized controlled trial to evaluate this approach in CRS is currently recruiting patients. The measures of CRS prevention /ICONS might include reduction of tumor cell burden prior to infusion and limitation of the number of infused CAR-T cells. Refractory ICANS may be treated by intratecal hydrocortisone and methotrexate [46].
Macrophage activation syndrome is difficult to diagnose and to treat. As it was demonstrated by Sandler et al., 70% of the reported EBMT centres did not use standard screening protocols, but, at least, ferritin level might be used as a common screening marker [47]. A differing variety of HLH treatment is also applied. Emapalumab and anakinra may be among potential new therapeutic options, due to their anti-inflam-atory effect [48].
Pulmonary, cardiological and metabolic side effects of CAR-T cells also observed in clinics. Cardiovascular events are more frequent in patient with CRS using troponin as a bi-omarker. Severe cytopenias after CAR-T therapy had no significant impact on overall survival but progression-free survival was poorer in patients with this complication. G-CSF and eltrombopag or autologous Bck up might be considered a treatment option [49].
Acute and chronic graft-versus-host disease
New EBMT Consensus Recommendations for the management of GvHD were presented by Olaf Penack. [50]. According to the recommendations, ruxolitinib is recommended in adults for steroid-refractory both acute and chronic GvHD, whereas belumosudil and ibrutinib could be potential options for steroid-refractory chronic GvHD. For the prevention of GvHD, ATG is recommended for matched related allo-HSCT with post-transplant cyclophosphamide as a therapeutic option. In matched and mismatched unrelated allo-HSCT, ATG or PT-Cy are recommended. Among Springer Clinical Award winners was the research presented by I. Moiseev et al. aiming to compare GvHD prophylaxis with tacrolimus and mycophenolate mofetil versus ruxolitinib after PT-CY which demonstrated a favourable safity profile [51].
Survivorship in chronic GvHD
Helene Schoemans made a presentation of new insights on chronic GvHD from the EUROGRAFT COST Action, announcing a number of recent publications and activities in the field [52]. COST-EBMT survey highlighted the necessity of NIH criteria in order to evaluate cGvHD response to the treatment, as well as recognized a lack of actual biomarkers for this condition.
According to the work of Majhail et al., about 500 000 HSCT survivors are estimated to be in the US alone by 2030 with 14% of them to be survivors of childhood HSCT [53]. Rachel Phelan from the USA made an introduction of updated HCT survivorship guidelines which include over 140 graded recommendations for clinical care [54].
Posttransplant infections
This year, the session of Infectious Diseases Working Party was devoted to most relevant HSCT topics, such as early discontinuation of antibiotics in neutropenic patients, spotlighted by Dina Averbuch. As already known, early discontinuation of empiric antibacterial therapy of febrile neutropenia in allo-HSCT recipients is feasible [55]. Another highlight was the revised Guidelines for Management of Toxoplasmosis by Catherine Cordonnier, presented earlier at 9th ECIL meeting. Key message is a recommendation of qPCR screening and pre-emptive treatment in all Toxo-sero-positive patients [56].
Several sections were devoted to post-HSCT viral infections. Focus was made on the optimization of cytomegalovirus (CMV) infection management, especially prophylaxis and refractory/resistant disease. The issue of letermovir CMV prophylaxis in HSCT patients remains a central problem. The speakers highlighted both the available data on the effectiveness of letermovir and presented new ones [57, 58]. Dr. Perales (Memorial Sloan Kettering Cancer Center) presented the study: Extension of Letermovir (LET) From Day 100 to Day 200 Post-transplant for the Prevention of CMV Infection in HSCT Participants (NCT03930615). Preliminary results showed that letermovir prophylaxis from 100 days to 200 days post-HSCT was superior to placebo in the prevention of clinical-significant CMV infection (2.8% vs
18.9%, p=0.0005). However, there was no significant impact on all-cause mortality [59].
Also, new anti-CMV drug - maribavir, was in the spotlight. Several speakers presented the results of Phase 3 AURORA study assessing the efficacy and safety of maribavir compared to valganciclovir for the treatment of CMV infection in hematopoietic stem cell transplant (HSCT) recipients. Maribavir demonstrated efficacy in confirmed CMV viremia clearance but did not meet its primary endpoint of non-inferiority versus valganciclovir (maribavir 69.6% vs. valganci-clovir 77.4%; adjusted difference -7.7%; 95% CI: -14.98, -0.36) [60].
Close attention was also paid to refractory/resistant CMV infection. Several speakers presented the results of SOLSTICE study: efficacy of maribavir therapy of refractory CMV in HSCT and solid organ transplant recipients. A significantly higher proportion of patients achieved primary endpoint of confirmed viremia clearance at week 8 compared with investigator-assigned therapy (55.7% vs 23.9%) [61].
Another important presentation was made by Dr. Styczyn-ski: Frequency, management and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HSCT. It's analysis of the survey results performed by Infection Disease Working Party, which included 111 transplant centers and summarized the real-world data dealing with EBV issue. The study will become strong basis for addition to current guidelines [62].
The key take-home message that we are dealing with a paradigm shift regarding management of viral infections, especially CMV, which makes us one step closer to improving the outcomes of HSCT in nearest future.
Intensive care & transfusion: Overall tendencies
If compared with previous EBMT congresses, the scientific program in these topics shows a decrease in the number of studies devoted to transfusion medicine, except topic of extracorporeal photopheresis for GvHD treatment. The sections dedicated to intensive care were not presented at all, except the occasional studies on veno-occlusive liver disease (see above), hemorrhagic cystitis. Severe infectious complications were traditionally paid a lot of attention (see above).
Supportive care and nutrition aspects in HSCT
Of note, a significant increase in nurse's sessions, during which the vast majority of reports related to supportive care and nutritional support (NS) were presented. The reports' quality level varies greatly from so-called "refreshing" to high-tech with a competent study design. It is important to clarify that the basic educational process and further nurse's specialization in Europe and Russia differ significantly from each other, which diversifies the degree of responsibility in medical practice and involvement in the scientific process.
A quite small scientific activity - 6 reports (5 of them in the nursing sections) and 10 posters - were devoted to nutritional status and NS. At the same time, the need for NS in HSCT is currently beyond doubt, given the negative impact of malnutrition on overall survival and the risk of post-transplant complications severity worsening.
In particular, a high demand for NS was shown again in 51% of auto-HSCT recipients [63]. Almost all participants emphasized the need for dietitian as a member of multidisci-plinary team to organize personalized nutritional counseling during HSCT, which led to the correction of both nutritional status and quality of life [64].
At the same time, it is important to realize that not only malnutrition is a challenge, but obesity also, which can often be accompanied by diabetes mellitus. For example, the EBMT working group, using the example of more than 36 thousand recipients, found out that the presence of obesity or diabetes prior to allogeneic HSCT did not influence the risk of developing grade II-IV acute GvHD, but was associated with an increased risk of death after being diagnosed with acute GvHD [65].
An important aspect in the implementation of NS is the estimation of the actual energy expenditure and protein requirements, especially in the pediatric cohort of patients. Colleagues from Denmark, based on indirect calorimetry data, paid attention to the fact that energy needs in young children in the early posttransplant period (D+1 - D+14) often do not correlate to worldwide known calculations and are an unstable parameter, which can lead to overfeeding and metabolic disorders [66]. Similar, but less pronounced changes were obtained in the sample of adult patients with allo-HSCT, thus making it possible to use recommended EBMT values of 25-30 kcal/kg actual energy consumption in patients in a stable condition [67].
Over recent years, the advantages of self-alimentation, sipping and enteral nutrition have been repeatedly proven in comparison with parenteral nutrition, including in the context of a protective effect on the intestinal microbiota. This is reflected in the gradual shift from the traditional low-mi-crobial diet and loosening the restrictions, except of intestinal GvHD conditions, which require a sparing diet [68. Physicians from Austria (St. Anna's Kinderspital Vienna) and Germany (Medical Center Hamburg-Eppendorf UKE) in backstage conversations also confirmed similar practical approaches.
Maintaining a balanced and familiar diet for the patient is a prerequisite for the prevention of emerging micronutrient and vitamin deficiencies. The role of vitamin D in the context of HSCT is in the trend of researchers. In particular, low vitamin D levels before allo-HSCT correlated with increased D+100 mortality, risk of acute GvHD (n=100) [69] and significantly higher risk for the development of chronic GvHD than those patients without vitamin D deficiency (n=186) [70]. However, researchers from the Netherlands have not identified positive effects of supplemental vitamin D therapy in adults with MM and lymphomas with auto-HSCT (n=44), but marked that in other types of treatment, the relevance of vitamin D may be of greater value [71].
In an attempt to improve the prevention of nausea and vomiting during the conditioning regimen and, thereby, maintain adequate food intake, a convincing effectiveness (91% of adult allo-HSCT recipients did not suffer any emetic episodes) was shown with three-drug antiemetic therapy containing a neurokinin-1 receptor antagonist, a 5-hydroxy-tryptamine 3 (netupitant-palonosetron) and low dose dexa-methasone was obtained with a good tolerability profile [72].
Interesting data were demonstrated by the researchers from England, who suggested using antimotility agents in adult patients with auto-HSCT (n=76) since the conditioning regimen and in the early post-transplant period, given that toxic diarrhea can occur in almost every patient, whereas infections, including Clostridium difficile-associated, are quite rare. According to their positive experience, they recommend that antimotility agents started since the outset of diarrhea, unless there is bloody stool, severe abdominal pain or cardiovascular instability [73].
The debatable question still remains in the area of prolonged enteral nutrition, or when indications for gastrostomy appear, because the tube installation criteria in HSCT have not been determined due to the potential risks of infectious and hemorrhagic complications. The first experience is quite encouraging both during the preventive installation of a percutaneous endoscopic gastrostomy in children (n=24) [74], and in the post-transplant period (n=25) against the background of various complications and dysfunction of the digestive system [75]. The obtained data demonstrate the relative safety of percutaneous endoscopic gastrostomy in al-lo-HSCT patients and sufficient clinical efficacy to maintain and improve nutritional status in presence of severe digestive system dysfunction. There were typical minor (80-100% and 20%) and major (0-20% and 4%) complications, but their reliable frequency and impact on overall survival have not yet been determined due to limited experience.
Pediatric transplantation
Malignant disorders, conditioning regimens
At the Pediatric Disease Working Party Session (PDWP), Prof. P. Bader and Prof. R. Handgretinger. discussed optimal conditioning regimen for pediatric ALL, i.e., total body irradiation (TBI) versus chemotherapy [76]. The authors demonstrated superiority of TBI as based on results of phase III study FORUM (EudraCT 2012-003032-22; ClinicalTrials. gov: NCT01949129). In this study, 417 patients (< 18 years at diagnosis, 4-21 years at HSCT) with HLA-compatible related or unrelated donor were randomly assigned over 20132018. Of them, 212 patients received TBI (a total of 12 Gy) and etoposide, and 201 received chemoconditioning fludara-bine, thiotepa, and either busulfan or treosulfan. At a median follow-up of 2.1 years, overall survival (OS) was significantly higher following TBI vs chemoconditioning, with a 2-year probability of OS (91% vs 75%, P < .0001). Two-year EFS was significantly higher following TBI vs chemotherapy (86% vs 58%, P < .0001). Cumulative incidence of relapse was 12% in a TBI group against 33% in the chemoconditioning groups (P <.0001). Also, TBI was associated with lower toxicity and transplant-related mortality (TRM) than chemoconditioning:
2% versus 9% (P = .027). However, the downside of TBI is presented by secondary malignancies. In this study (a total of 558 pediatric patients), secondary malignant neoplasms (SMN) were diagnosed in 33 cases following TBI (34 solid tumors, 5 MDS/AML), thus being significantly increased against those without TBI (p = 0.045), the cumulative incidence of a SMN was in patients who had received TBI/VP versus [Peter Bader, Paed 1-2]. Therefore, the A.Spyridonis (OS15-01], as based on results of ALWP group in adult ALL, proposed reduction of the TBI dose down to 8 Gy for maintaining leukemia-free survival (LFS) and decreasing long-term toxicity [77]. Meanwhile, is too early to conclude that TBI is a standard for pediatric ALL. Prof. R. Handgretinger reminded about importance of cumulative AUC pattern of chemotherapy drugs used in conditioning (e.g., busulfan and treosulfan) for survival and toxicity profile after allo-HSCT [76].
Prof. Christina Peters reported the results of a prospective FORUM study for young children <4 y.o. (n=202) treated with HSCT from HLA-compatible donors, using conditioning with fludarabine, thiotepa, and either busulfan, or treosulfan, with TBI/VP16 applied in few cases. After the median follow-up of 3 years, OS was 68%; EFS was not so good (51%). One-year TRM was below 10%, but incidence of relapse was worse than in older patients (40%). The relapse incidence and TRM was comparable for busulfan and treo-sulfan conditioning group. For the youngest recipients (<1 y.o.), EFS was poor, with 27% only [78].
Another treatment option for young children was demonstrated by Dr. Sara Ghorashian who presented data of international, multicentre, retrospective study which included 35 (92%) patients with ALL <3 years old who received the CAR-T cells (Tisagenlecleucel) infusions. Among 28 patients who received an infusion, and in whom response could be assessed, 24 (86%) showed a complete response. Overall survival at 6 and 12 months was 84% and 88%, respectively. EFS at 6 and 12 months was, resp., 75% and 69%. CIR was 25% at 12 months. No therapy-related severe neurotoxicity and deaths were observed. Importantly, that relapse risk was not significantly increased in patients with KMT2A-rearranged leukaemia. No cases of lineage switch were registered by the cut-off date [79].
Great attention was paid to the role for cord blood transplantation in malignant and non-malignant disease. Prof. V. Rocha demonstrated very good results of a retrospective studies when combining data from Eurocord and Duke University on 4834 children transplanted with a single unrelated CB units (CBU) from 1993 to 2019. OS rates were found to be improved significantly over time: The probability of 5-year OS for patients with leukemia was 47.2% and increased from 37.1% to 52.9% during last years. According to new data from 367 patients in the UK and Ireland undergoing T-cell-repleted cord blood (112 patients) or other cell sources (255 patients), SCT improves disease-free survival, relapse risk and reduces chronic GvHD in pediatric AML/MDS. Such excellent results may be achieved by a very low incidence of HLA loss (1%) after UCBT. Thus, UCB availability, low disease relapse, and good transplant function make CB relevant for pediatric transplantation [80].
In the setting of posttransplant relapse, P. Bader showed efficacy of CD-19-CAR-T cells therapy for children with ALL. In the retrospective study 65 patients were included with the median age 10 years. Most patients received low dose chemotherapy before CAR-T cells therapy. Half of patients were in hematological remission (<5% blasts) before low dose chemotherapy (LDC), other had open disease (>=5% blasts). Cytokine release syndrome (CRS) was observed in 67%, CRS+ICANS, in 8%. At day 28, complete hematological remission was achieved in 88% of patients, complete hema-tological remission in 10%, 2 patients died from CRS and severe infectious. EFS at 2 yrs was 43%, OS was 53%. Disease burden at LDC did not influence significant on outcomes. Time of relapse after allo-HSCT was important of prognosis after CAR-T cells therapy. Patients who relapsed at > 6 months from allo-HSCT had an excellent prognosis with only a single Tisacel infusion, whereas patients with relapse <6 months had a poor prognosis (p<0.001) [81].
Non-malignant disorders
Prof. Josu De La Fuente reported advances in conventional treatment and gene therapy for b-thalassemia. He presented a study of therapy based on autologous cell transplantation with the addition of the bA-T87Q gene-modified stem cells. Of the 60 patients initially treated with betibeglogene autotemcel (beti-cel) included into Phase 1/2 and 3 of clinical trials, 32 patients were observed in the LFT 303 study, which evaluated the safety profile, as well as the duration of therapeutic effect. All patients are alive after the 2-year follow up. None of the patients showed in vivo replication of the introduced viral vector, as well as adverse events associated with genetically modified cells. Among the patients in Phase 1/2, 64% achieved transfusion independence with a duration of response of 51.2 months. In 90% of patients who received an improved version of cells (from phase 3 studies), blood transfusion was not required within 26.1 months. All the patients who became independent on blood transfusions retain it at the time of the last contact. Impressive results are also obtained with an alternative gene therapy strategy implying a knockout of the BCL11A gene responsible for silencing the Hb g-chain gene, thus causing stimulation of HbF production. All 44 patients with transfusion-dependent ^-thalassemia (TDT) and sickle cell disease (SCD) infused with Exa-cel after busulfan-based conditioning regimen showed engraftment. Forty-two out of 44 patients are transfusion-free. Two patients had not yet canceled transfusions but have 75% and 89% reductions in transfusion volume [Josu De La Fuente] [82].
Anthea Guha presented the initial results of NCT04201405 clinical trial (phase I/II) of autologous HSC transduced ex vivo with CD11b lentiviral vector encoding for human SGSH in patients with mucopolysaccharidosis (MPS) Type IIIa (Sanflippo syndrome type A). So far, HSCT with full donor chimerism is only curable approach. However, it should be done early in life to prevent neurological impairment. The proposed method is aimed for achieving overexpression of the deficient SGSH enzyme, in order to stop the present organ damage and ensure normal development. At the time of the last contact, all patients (n=5) are alive (duration of follow-up, 9 to 18 months). In 100% of cases, it was possible to achieve normal or increased levels of the enzyme in blood
and CSF. From the sixth month of observation, the level of heparansulfate was reduced to normal values in blood, urine and CSF. Gain of skills was in line with development of normal children in 4 out of 5 patients [83].
Dr. M. E. Bernardo has demonstrated primary data from a phase I/II clinical trial of gene therapy using lentiviral platform for patients with MPS Type 1 (Hurler subtype). Overall, 8 patients have received treatment followed by a median follow-up of 3.7 years. At the time of last examination, all patients were alive, 100% had supraphysiological levels of a-L-iduronidase enzyme, and a decrease in dermatan sulfate in urine to the reference values at 1 year after transplantation of genetically modified cells. The author paid special attention to skeletal outcomes: all patients who received gene therapy exhibited longitudinal growth within expected reference ranges according to age and gender, with median height gain being greater than that one observed in a cohort of HSCT patients. Also, stabilization of kyphosis and normalization of joint mobility and motor skills were observed. In addition, the author mentioned initiation of clinical trials on other enzymopathies (i.e., Type III MPS and type 3 Gausher disease). For type 3 Gausher disease, the first transplantation of modified cells has already been carried out with a positive result, i.e., in reaching the normal levels of the ^-glucocere-brosidase and stabilization of CNS disease [84].
Dr. Alexandra Laberko, our Russian colleague (Dmitry Ro-gachev National Research Center, Moscow) reported outcomes of ten-year experience of TCRab/CD19 depletion for HSCT in 299 patients with inborn errors of immunity. En-graftment was achieved in 93%. The rate of graft failure was significantly higher after one alkylating drug (Treosulfan) in condioning regimen versus two alkylators (Treosulfan+Mel-phalan). Also, the rate of graft failure was higher in ATGAM serotherapy in comparison to Thymoglobulin. Incidence of acute GvHD was 29%, the rate of aGvHD was significantly higher in patients treated with ATGAM versus Thymoglobu-lin. Incidence of chronic GvHD was 9%. The 5-year OS was 73% [85].
Supportive care for HSCT complications
Dr. Sylvain Choquet presented the results from a multicenter, open-label Global Phase Study of Tabelecleucel (Tab-Cel) for refractory EBV-positive posttransplant lym-phoproliferative disease (PTLD) following allogeneic HSCT, or solid organ transplant. Tabelecleucel is a preparation of allogeneic, EBV-specific cytotoxic T-cells which targets and eliminates EBV-infected cells in a human leukocyte antigen (HLA)-restricted manner. It is made of allogeneic cells taken from the recipient mixed with EBV-infected B-cells from the same donor. As of November 2021, 43 patients (2 of them were children) received, at least, one dose of study treatment and were included in the analysis. ORR of 51.2 was registered among the entire group of patients, with CR of 27.9%, or PR of 23.2%. Median duration of response was 23 months. Estimated median OS of 18.4 months, and patients responding to Tab-cell had a longer survival compared with non-re-sponders (OS at 1 year: 84.4% vs 34.8%) [Sylvain Choquet] [86].
Prof. Franko Locatelli presented the first data from REACH4 (NCT03491215), a Phase I/II open-label, single-arm, multi-
center Study of JAK1/2 inhibitor Ruxolitinib added to corticosteroids in pediatric patients with treatment-Naive or Steroid-Refractory acute GvHD. Overall, 45 patients were treated with Ruxolitinib at the different starting dose depending of the age. In preliminary efficacy analysis, the overall response rate at day 28 in all patients was 84.4%, being 69.2% among treatment-naive and 90.6% among steroid-refractory patients [87].
Dr. Thibaut César reported on the effectiveness of Letermo-vir for CMV prophylaxis infection in very high-risk patients transplanted for primary immunodeficiencies. The study included 31 patients who underwent 36 HSCTs, and 62 patients of historical control group. The indication for Leter-movir prophylaxis was the CMV-seropositivity of the recipient, or donor seropositivity, or CMV viremia detected within 3 weeks before transplantation. The drug was initiated on D0, it was well tolerated and stopped at the median of 155 days after HSCT. In the Letermovir group, CMV reactivation was observed in 5 patients (14%) versus 28 patients (45%) in the historical control group, p=0.002. Survival without significant CMV infection in the Letermovir group was significantly higher than in the control group, p=0.09 [88].
Poster session
R. Gorbacheva Memorial Research Institute presented 4 posters on pediatric HSCT: "Haploidentical versus matched unrelated HSCT with post transplant cyclophosphamide based GvHD prophylaxis in children with acute leukemia" [89], "Combined immunotherapy after haplo-HSCT in infants ALL with KMT2A rearrangement" [90], "Loss of het-erozygosity (LOH) in the HLA region in pediatric patients with relapse of hematological malignancies after haploiden-tical HSCT" [91], "Allogeneic hematopietic stem cell transplantation in patients with anaplastic large cell lymphoma (ALK+)" [92]. Our colleagues from Dmitry Rogachev National Research Center were awarded for 2 posters: the first of them concerns outcomes of HSCT with TCRab/CD19 depletion in cohort of inborn errors of immunity with hemophagocytic lymphohistiocytosis [93], and the second concerned influence of active complications at HSCT upon survival post-HSCT in inborn errors of immunity [94].
Acknowledgements
The study was funded by a grant from Russian Science Foundation № 22-15-00491, https://rscf.ru/project/22-15-00491/
References
1. Esteve J, New insights from AML classification. 2023. EBMT Meeting: ALWP-2.
2. Kharfan-Dabaja MA. Second allo-HSCT or DLI for relapsed AML? EBMT Meeting. 2023: W09-1.
3. Glass B. Comparison of allogeneic hematopoietic stem cell transplantation with chimeric antigen receptor T-cells in relapsed and refractory large B cell lymphoma. EBMT Meeting 2023: SS06-1.
4. Glass B. Report of LWP activities & introduction. Jiang Jiang Luan award. EBMT Meeting 2023: LWP-1.
5. de Masson A, Luan JJ: Allogeneic transplantation in advanced cutaneous T-cell lymphomas: a propensity score-matched controlled prospective trial. EBMT Meeting 2023: LWP-2.
6. Sockel K. Utilising molecular data to guide the transplant decision in myelofibrosis, EBMT Meeting. 2023: CMWP-1.
7. Boluda JCH. Selecting the best conditioning regimen (+/-GvHD prophylaxis) in allo-HCT for myelofibrosis. EBMT Meeting 2023: CMWP-4.
8. McLornan D. Transplant algorithm in MPN. EBMT Meeting 2023: E02-3.
9. Czerw T. Selecting the best donor and stem cell source in allo-HCT for Myelofibrosis EBMT Meeting 2023: CMWP-3.
10. Polverelli N. Optimal management of splenomegaly pre-transplant. EBMT Meeting 2023: CMWP-2.
11. Campodonico E. Pre-transplant splenic radiotherapy in patients affected by high-risk idiopathic/secondary myelofi-brosis undergoing allogeneic hematopoietic stem cell therapy (HSCT). EBMT Meeting 2023: 0S17-07.
12. Reis E, et al. Discovery of INCA033989, a monoclonal antibody that selectively antagonizes mutant calreticulin on-cogenic function in myeloproliferative neoplasms. 64 ASH Annual Meeting, December 10-13, 2022.
13. Passamonti F, Foran JM, Tandra A, De Stefano V, Fox ML, Mattour AH et al. The combination of navitoclax and ruxol-itinib in JAK inhibitor-naive patients with myelofibrosis mediates responses suggestive of disease modification. Blood. 2022; 140 (Suppl 1): 583-585. doi: https://doi.org/10.1182/ blood-2022-157949
14. Finazzi MC. Prospective validation of the prognostic impact of high molecular risk mutations after allogeneic stem cell transplation in myelofibrosis. EBMT Meeting 2023: OS17-03.
15. Polverelli N. Impact of comorbidities and BMI on the outcomes of allogeneic hematopoietic cell transplantation in myelofibrosis: an international analysis on behalf of the CMWP of EBMT. EBMT Meeting 2023: 0S17-01.
16. Gurnari C. Outcome prediction in patients with myel-odysplastic syndrome undergoing hematopoietic cell transplant in the molecular era of IPSS-M. EBMT Meeting 2023: OS17-05.
17. Mascarenhas O, Kremyanskaya M, Patriarca O, Harrison C, Bose P, Rampal RK, et al. Bet inhibitor pelabresib (cpi-0610) combined with ruxolitinib in patients with myelofibrosis - JAK inhibitor-naive or with suboptimal response to ruxolitinib - preliminary data from the manifest study. EHA Library. 2022; 06/11/2022; 357062; S198.
18. Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Pérez WS, Ana-setti C et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104(2):579-585. doi: 10.1182/blood-2004-01-0338
19. Lindholm C, Olofsson E, Creignou M, Nilsson L, Gare-lius HG, Cammenga J, et al. Failure to reach hematopoietic allogenic stem cell transplantation in patients with myelod-ysplastic syndromes planned for transplantation: a population-based study. Bone Marrow Transplant. 2022; 57(4):598-606. doi: 10.1038/s41409-022-01582-0
20. Robin M. Transplant algorithm in: MDS. EBMT Meeting 2023: E02-1.
21. Rovo A. Outcomes of CMML patients undergoing allogeneic HST in comparison with MDS patients - a retrospective analysis on behalf of the CMWP of the EBMT. EBMT Meeting 2023: 0S17-04.
22. Onida F. Transplant algorithm in: CMML. EBMT Meeting 2023: E02-3.
23. Mei M, Pillai R, Kim S, Estrada-Merly N, Afkhami M, Yang L, et al. The mutational landscape in chronic myelo-monocytic leukemia and its impact on allogeneic hemato-poietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis. Haematologica. 2023; 108(1): Jan 2023. doi: 10.3324/haema-tol.2021.280203
24. Baranwal A, Mangaonkar A, Shah MV, et al. High EASIX score is an independent predictor of non-relapse mortality in patients with CMML undergoing allogeneic stem cell transplant. Bone Marrow Transplant. 2022; 57:1842-1844. doi: 10.1038/s41409-022-01829-w
25. Vlasova Yu. Asciminib as a bridge therapy before alloge-neic hemopoietic stem cell transplantation for chronic mye-loid leukemia. EBMT Meeting 2023: 0S17-08.
26. Corbacioglu S. Sickle cell disease. EBMT Meeting 2023: E03-1.
27. Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A et al. HOPE trial investigators. A Phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019; 381(6):509-519. doi: 10.1056/NEJMoa1903212
28. Neumayr LD, Hoppe CC, Brown C. Sickle cell disease: current treatment and emerging therapies. Am J Manag Care. 2019; 25(18 Suppl):S335-S343. PMID: 31809007
29. Kutlar A, Kanter J, Liles DK, Alvarez OA, Cançado RD et al. Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis. Am J Hematol. 2019; 94(1):55-61. doi: 10.1002/ajh.25308
30. Cronin RM, Lin CJ, Chiang C, MacEwan S, DeBaun MR, Hyer JM. The use of FDA-approved medications for preventing vaso-occlusive events in sickle cell disease. Blood Adv. 2023; bloodadvances.2022008965. doi: 10.1182/bloodadvances. 2022008965
31. Teixeira Cottas de Azevedo J. Long-term side effects of allogeneic transplantation in SCD patients. EBMT Meeting 2023: E03-2.
32. De La Fuente J. Thalassaemia: advances in conventional transplantation & gene therapy. EBMT Meeting 2023: E03-3.
33. Griffin M. AA PNH and COVID: all what you want to know in 2023. EBMT Meeting 2023: SAAWP-1.
34. Giardino S. HLA-haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes. EBMT Meeting 2023: SAAWP-2.
35. Kulasekararaj A. RACE bio: state of the art. EBMT Meeting. 2023: SAAWP-4.
36. Mohty M. The headlines: where are we today with hepatic VOD? EBMT Meeting 2023: IS28-1.
37. Sureda A, Mohty M, Pagliuca A. The great debate: are we identifying severe hepatic VOD patients every time? EBMT Meeting 2023: IS28-2.
38. Mohty M. EBMT adult diagnostic criteria: where do we stand? EBMT Meeting 2023: IS28-3.
39. Avenoso MKD. Focused evaluation: the ward round protocol. EBMT Meeting 2023: IS28-7.
40. URL: https://www.ebmt.org/education/apps (Access: 19.06.2023)
41. Mohty M, Blaise D, Peffault de Latour R, Labopin M, Bourhis JH, Bruno B, et al. Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study. Bone Marrow Transplant. 2023; 58(4):367-376. doi: 10.1038/s41409-022-01900-6
42. Colecchia A. Liver stiffness measurement to aid early recognition. EBMT Meeting 2023: IS28-6.
43. Schoettler ML, Bhatt H, Vasu S. A systematic review of diagnostic, prognostic, and risk blood and urine biomark-ers of transplant-associated thrombotic microangiopathy. Front Immunol. 2023; 13:1064203. doi: 10.3389/fimmu. 2022.1064203
44. Schoettler ML, Carreras E, Cho B, Dandoy CE, Ho VT, Jodele S, Moissev I, et al. Harmonizing definitions for diagnostic criteria and prognostic assessment of transplantation-associated thrombotic microangiopathy. Transplant Cell Ther. 2023; 29(3):151-163. doi: 10.1016/j.jtct.2022.11.015
45. Scordo M. The lectin pathway's role in HSCT-TMA. EBMT Meeting 2023: IS08-4.
46. Koenecke C. New aspects in the management of CAR-T complications. EBMT Meeting 2023: TCWP-1.
47. Sandler RD, Tattersall RS, Schoemans H, Greco R, Ba-doglio M, Labopin M et al. Diagnosis and management of secondary HLH/MAS following HSCT and CAR-T cell therapy in adults; A review of the literature and a survey of practice within EBMT centres on behalf of the Autoimmune Diseases Working Party (ADWP) and Transplant Complications Working Party (TCWP). Front Immunol. 2020; 11:524. doi: 10.3389/fimmu.2020.00524
48. Cheloff AZ, Al-Samkari H. Emapalumab for the treatment of hemophagocytic lymphohistiocytosis. Drugs Today (Barc). 2020; 56(7):439-446. doi: 10.1358/dot.2020. 56.7.3145359
49. Patel NP, Doukas PG, Gordon LI, Akhter N. Cardiovascular Toxicities of CAR T-cell Therapy. Current oncology reports. 2021; 23(7) [78]. doi: 10.1007/s11912-021-01068-0
50. Penack O. New EBMT consensus Recommendations for the management of GvHD. EBMT Meeting 2023: TCWP-2.
51. Moiseev IS. Multicenter randomized phase ii clinical trial to compare graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil versus ruxolitinib after post-transplant cyclophosphamide (PTCYRUXO). EBMT Meeting 2023: P302.
52. Schoemans H. New insights on chronic GvHD from the EUROGRAFT COST Action. EBMT Meeting 2023: TCWP-3.
53. Majhail NS, Rizzo JD. Surviving the cure: long term followup of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2013; 48(9): 1145-1151. doi: 10.1038/ bmt.2012.258
54. Phelan R. Updated HCT survivorship guidelines - an international consensus effort. EBMT Meeting 2023: TCWP-4.
55. Averbuch D. What is new in the management of neutropenic fever. EBMT Meeting 2023: IDWP-1.
56. Cordonnier C. How to prevent and treat toxoplasmosis in HSCT patients - New ECIL recommendations. EBMT Meeting 2023: IDWP-3.
57. Ljungman P. CMV in HSCT: Current Challenges and Controversies. EBMT Meeting 2023: IS07-2.
58. Stelljes M. Real world evidence: What has the past CMV experience taught US? EBMT Meeting 2023: IS07-3.
59. Perales MA. Emerging New Data: Building Blocks for Future CMV Management; IS07-4.
60. Kotton C. Updating the Status Quo for CMV Management. EBMT Meeting 2023: IS23-4.
61. Alain S. Refractory and Resistant CMV in HSCT Patients. EBMT Meeting 2023: IS12-4.
62. Styczynski J. Frequency, management and new treatment modalities of EBV-DNA-emia and EBV-PTLD after Allo-HCT: survey of IFWP-EBMT. EBMT Meeting 2023: OS08-07.
63. Mace V, Biglin S, Hallam S, Truelove E, Gimeno H. Energy intake, level of nutrition support and symptoms following stem cell transplantation. A retrospective, observational study. EBMT Meeting 2023: P499.
64. Loschi M, Estran S, Soldati A, Benachour S, Chibois J, Cluzeau T. Personalized nutritional management and nutritional support after allogeneic stem cell transplantation significantly decrease malnutrition and improve quality of life: results of the ALLONUT trial. EBMT Meeting 2023: OS 10-05.
65. Gjœrde L, Ruutu T, Peczynski C, Boreland W, Kröger N, Blaise D, Schroeder T, de Latour R, Gedde-Dahl T, Kulagin A, Sengelov H, Yakoub-Agha I, Finke J, Eder M, Basak G, Moiseev I, Schoemans H, Koenecke C, Penack O, Peric Z. Pretransplantation diabetes mellitus and obesity and acute
graft-versus-host disease after allogeneic stem cell transplantation: a study from the EBMT transplant complications working party. EBMT Meeting 2023: P363.
66. Pedersen L, Kielsen K, S0rum M, Kok K, Masmas T, If-versen M, M0lgaard C, Müller K. Nutritional energy requirements in pediatric patients undergoing stem cell transplantation measured by indirect calorimetry. EBMT Meeting 2023: P478.
67. Kucher M, Saltykova N, Volkova A, Shcherbakov A, Ku-lagin A. Nutritional status evaluation via bioimpedance and indirect calorimetry in adult patients with allogeneic HSCT. EBMT Meeting 2023: P491.
68. Van der Linden N. Nutrition post-SCT and the "Graft Diet". EBMT Meeting 2023: NG16-2.
69. Uygun V, Daloglu H, Öztürkmen S, Yalçin K, Karasu G, Yesilipek A. Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after stem cell transplantation in thalassemia major patients. EBMT Meeting 2023: P488.
70. Gruhn B, Wittig S, Schneider H. Impact of vitamin D level on outcome after allogeneic hematopoietic stem cell transplantation in childhood. EBMT Meeting 2023: P635.
71. Van Gorkom G, Boerenkamp L, Gijsbers B, van Ojik H, Wodzig W, Wieten L, van Lessen C, Bos G. No effect of vitamin administration on neutrophil recovery in autologous stem cell transplantation for myeloma or lymphoma: a blinded, randomized placebo-controlled trial. EBMT Meeting 2023: P034.
72. Spina A, Urbano M, Marchionne F, Schifone C, Mascio-pinto P, Quintana G, Male G, Pastore D. Efficacy and safety of netupitant/palonosetron combination ((NEPA) and low dose of dexamethasone in preventing nausea and vomiting in patients undergoing allogeneic stem cell transplantation. EBMT Meeting 2023: P486.
73. Cakmak S, Pierre J, Munir S, Taylor J, Agrawal S, Lam-bourne J. Management of diarrhea in haemato-oncology: changing the flow. EBMT Meeting 2023: P484.
74. Evans J, Green D, O'Connor G, Lanigan J, Gibson F. Similar outcomes but different experiences of gastrostomy versus nasogastric tube feeding in pediatric bone marrow transplant: a mixed methods study. EBMT Meeting 2023: NG14-03.
75. Kucher M, Shvetcov A, Gurgenidze N, Saltykova N, Kon-drashov M, Kulagin A. Percutaneous gastrostomy in alloge-neic hematopoietic stem cell transplantation. EBMT Meeting 2023: P504.
76. Bader P, Handgretinger R. TBI or nor TBI as standart of care in ALL; Pro,s and Con,s. EBMT Meeting 2023: Paed1-3.
77. Spyridonidis A. Matched-paired comparison of 12-Gy or 8-Gy total body irradiation for acute lymphoblastic leukemia patients in first complete remission. On behalf of the ALWP of EBMT. EBMT Meeting 2023: OS15-01.
78. Peters C. Low toxicity with myeloablative chemo-based conditioning for children with ALL below 4 years of age. Results from the prospective multinational FORUM-Trial.
79. Ghorashian S. CART for relapsed of refractory B-ALL in children below 3 years. EBMT Meeting 2023: Paed1-2.
80. Rocha V. Is there a role for Cord Blood in HSCT in children in the future? EBMT Meeting 2023: Paed1-4.
81. Bader P. Acute lymphoblastic leukemia: CD-19-CAR-T CELLS are an effective therapy for posstransplant relapse. EBMT Meeting 2023: PAED3-06.
82. De La Fuente J. Thalassaemia: advances in conventional transplantation and gene therapy. EBMT Meeting 2023: E03-3.
83. Guha A. Biochemical engraftment and clinical outcomes of ex-vivo gene therapy for mucopolysaccharidosis Type IIIA. EBMT Meeting 2023: Paed4-06.
84. Bernardo MA. Gene therapy in metabolic disease. EBMT Meeting 2023: E11-2.
85. Laberko A. Ten-year single-center experience of TCR-AB-CD/19 Depletion for hematopoietic stem cell transplantation in inborn errors of immunity. EBMT Meeting 2023: OS04-07.
86. Choquet S. Updated results from phase 3 study Tabele-cleucel for post-transplant lymphopriliferative disease following allodeneic hematopoietic cell or solid organ transplant after failure rituximab (R) or Chemotherapy (allele). EBMT Meeting 2023: Paed3-02.
87. Locatelli F. Efficacy and safety of ruxolitinib in patients with steroid-refractory chronic graft-versus-host disease after crossover in the PHASE 3 REACH-3 Study. EBMT Meeting 2023: OS05-01.
88. Thibaut C. Od-label use of letermovir for CMV prophylaxis in very high0risk pediatric HSCT recipients. EBMT Meeting 2023: OS04-05.
89. Borovkova A, Paina O, Rachmanova Z, Kozhokar P, Frolova A, Tsvetkova L, et al. Haploidentical versus matched unrelated HSCT with post transplant cyclophosphamide based GvHD prophylaxis in children with acute leukemia. EBMT Meeting 2023: P351.
90. Paina O, Tsvetkova L, Rachmanova Z, Kozhokar P, Frolo-va A, Anna Osipova, et al. Combined immunotherapy after haplo-HSCT in infants ALL with KMT2A rearrangement. EBMT Meeting 2023: P642.
91. Tsvetkova L, Evdokimov A, Barkhatov I, Paina O, Kozhokar P, Frolova A, et al. Loss of heterozygosity (LOH) in the HLA region in pediatric patients with relapse of hematological malignancies after haploidentical HSCT. EBMT Meeting 2023: P026.
92. Galimov A, Lepik E, Kozlov A, Kazantsev I, Yuhta T, Tolkunova P, et al. Allogeneic hematopietic stem cell transplantation in patients with anaplastic large cell lymphoma (ALK+). EBMT Meeting 2023: P794.
93. Idarmacheva A, Laberko A, Sultanova E, Brilliantova V, Maschan A, Shelikhova L, et al. Outcome of HSCT on with AB-T cell depletion in a cohort of inborn errors of immunity with hemophagocytic lymphohistiocytosis. EBMT Meeting 2023: P755.
94. Laberko A, Sultanova E, Idarmacheva A, Skvortsova Yu, Rodina Yu, Shelikhova L, et al. Prognostic risk factors in he-matopoietic stem cell transplantation in inborn errors of immunity. EBMT Meeting 2023: P757.
Резюме
Статья содержит краткий обзор докладов и постер-ных сообщений, которые привлекли особый интерес российских участников ежегодного конгресса Европейской ассоциации трансплантации костного мозга (ЕВМТ-2023). Обзор представляет собой коллективный взгляд сотрудников НИИ детской онкологии, гематологии и трансплантологии им. Р. Горбачевой (С1С 725) на современные тенденции в области трансплантации гемопоэтических стволовых клеток при лечении лейкозов, лимфом, миелодиспласти-ческого синдрома, незлокачественных заболеваний системы крови - как у детей, так и у взрослых пациентов.
Ключевые слова
Трансплантация гемопоэтических стволовых клеток, конгресс EBMT-2023, обзор.
I Конгресс EBMT-2023: краткий обзор
Андрей М. Чекалов, Любовь А. Цветкова, Никита В. Левковский, Татьяна А. Рудакова, Максим А. Кучер, Александр А. Синяев, Александр Д. Кулагин
НИИ детской онкологии, гематологии и трансплантологии им. Р. М. Горбачевой, Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия
