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Abstract For most patients with childhood myelodysplastic syndrome (cMDS), allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remains the only curative option. In the case of increased blasts (cMDS‐IB), the benefit of pretransplant cytoreductive therapy remains controversial. In this multicenter retrospective study, the outcomes of all French children who underwent allo‐HSCT for cMDS reported in the SFGM‐TC registry between 2000 and 2020 were analyzed (n = 84). The median age at transplantation was 10.2 years. HSCT was performed from matched sibling donors (MSD) in 29% of the cases, matched unrelated donors (MUD) in 44%, haploidentical in 6%, and cord blood in 21%. Myeloablative conditioning was used in 91% of cases. Forty‐eight percent of patients presented with cMDS‐IB at diagnosis (median BM blasts: 8%). Among them, 50% received pretransplant cytoreductive therapy. Five‐year overall survival (OS), cumulative incidence of nonrelapse mortality (NRM), and relapse were 67%, 26%, and 12%, respectively. Six‐month cumulative incidence of grade II–IV acute graft‐versus‐host disease was 46%. Considering the whole cohort, age under 12, busulfan/cyclophosphamide/melphalan conditioning or MUD were associated with poorer 5‐year OS. In the cMDS‐IB subgroup, pretransplant cytoreductive therapy was associated with a better OS in univariate analysis. This seems to be mainly due to a decreased NRM since no impact on the incidence of relapse was observed. Overall, those data may argue in favor of cytoreduction for cMDS‐IB. They need to be confirmed on a larger scale and prospectively.

Abstract Defibrotide (DF) is indicated for the treatment of severe sinusoidal obstruction syndrome (SOS) following hematopoietic stem cell transplantation (HSCT), but its prophylactic use against SOS is not recommended yet. This study describes the impact of the preventive and curative use of DF on reducing the incidence and severity of SOS in children. Patients aged 0–19 years, who received allogenic HSCT after myeloablative conditioning regimen with busulfan or total body irradiation in our comprehensive cancer center, between 2013 and 2017, were included. The Baltimore or modified Seattle criteria were used for SOS diagnosis. SOS was graded using the 2017 European Society for Blood and Marrow Transplantation classification defining severity criteria of SOS in children. SOS occurrence tended to decrease with prophylactic DF, but no significant difference was observed in terms of severity. When not treated with preventive DF, 50% (19/38) of the patients with SOS were graded severe to very severe, but only 37% (7/19) had organ dysfunction. Curative DF was administered at a median of 2 days post‐HSCT, for a median of 6.5 days. The absence of fatal SOS supports the use of early curative DF with acceptable toxicities and questions the optimal duration of DF treatment.

Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, graft-versus-host disease (GvHD) and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT in two conventional situations: i) upfront allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GvHD, extensive chronic GvHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (hazard ratio [HR]=4.08; 95% confidence interval [CI]: 1.41-11.83; P=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR=1.04; 95% CI: 1.02-1.06; P

Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.

Documenting bacteremia at the onset of fever in immunosuppressed children is challenging; therefore, it leads to the early administration of broad-spectrum antibiotics. We aimed to analyse the evolution of antibiotic resistance profiles of bacterial bloodstream infections (BSI) and gut colonisations in a large cohort of immunocompromised children carrying a central venous catheter, in comparison with a prior, similar study conducted in our centre from 2014 to 2017. A retrospective, observational cohort study was conducted from January 2018 to December 2021, in a tertiary centre for paediatric immuno-haematology and oncology. Empirical antibiotic therapy was adapted to the immunosuppression risk group and prior bacterial colonisation. There was a mean of 6.9 BSI/1000 patient bed days. Multidrug-resistant bacteria (MDRB) associated BSI accounted for 35/273 (12.8%). The incidence of MDRB gum/gut colonisation and MDRB associated BSI increased annually and correlated with the level of immunosuppression (p = 0.024). One third (34.7%) of the BSI episodes were not associated with neutropenia. As compared to the previous study, an alarming emergence of MDRB responsible for gut colonisations and BSI in immunosuppressed children was reported over the last four years. The degree of immunosuppression directly correlates with the risk of having an MDRB gut colonisation or MDRB BSI.

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.

Since the end of the 20th century, architectural production, between sign and function, is a privileged resource for the public as well as private local actors looking for an image to promote their territories. The observation of an instrumentation of the « signed » and legitimized - on an international scale - architecture marks its entry into the competitive economy and the global system. The comprehension of globalization through architectural and urban design seems to find its limits if we read it as a result, but sounds relevant if we analyse it as a process. We assume the existence of « worlding » vectors (processes) which can propel the territories on the global archipelago. First amongst these vectors, architecture is one of the foundations of tglobal trajectories. More precisely, in the case of highly patrimonialized European cities such as Barcelona, Berlin and Rome, we observe the dialogic relationship between heritage and contemporary creation producing value and strengthening the « symbolic capital ». The architecture as a European worlding vector is questioned through actors’ strategies and metropolitan ambitions competing with heritage. Besides, this approach must be confronted, on one hand, with readings opposing local and global, or local sites and the global archipelago, and on the other hand, with those which analyse a syncretism of both scales.

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