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The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.

Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls. Access to these procedures as well as their financing differs significantly throughout Europe. As all European children and adolescents should have the same possibility, the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation organised an expert meeting in September 2015. This manuscript describes the recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who have to undergo an allo-HSCT.

In contrast to adults, 50% or more of medicines used in children have never been actually studied in the paediatric population in the European Union community (EU). Under the impression that compliance with good clinical practice (GCP) requirements will lead to an improved quality of clinical trials, the ratification of the EU Directive 2001/20/EG now imposes the same GCP regulations demanded for commercial clinical trials on non-commercial trials or so-called investigator-initiated trials (IITs). Although it is desirable that all clinical trials comply with ICH–GCP, ensuring that an IIT conforms creates a significant burden for the principal investigator, turning an IIT into a substantial logistic, administrative and financial enterprise. This can only be achieved with a multidisciplinary approach, including physicians, statisticians, data managers, administrators and others. In particular, ‘treatment optimization studies’—the most important clinical trials in paediatric oncology—are affected by this new law, potentially resulting in significant delays in the implementation of new and innovative treatment strategies in the paediatric population. This significant drawback was not foreseen but is now recognized and lead to measures to improve the situation for both non-commercial and paediatric clinical trials. Draft guidance on ‘specific modalities for non-commercial trials’, posted for comment last October, attempts to redress some of the research-crippling problems caused by the initial legislation; however, major problems remain. The EU regulation (EC) no. 1901/2006 ‘on medicinal products for paediatric use’ was enacted in January 2007. This new regulation is a promising step in the right direction, as it will facilitate the development and accessibility of medicinal products specifically for use in children. To adapt to and benefit from this new situation and encourage IIT, a coordinated approach of high expertise is necessary to support and guide the novice in the field of IIT to successfully launch, conduct and complete clinical trials especially in children.

Acute Graft versus Host Disease (aGvHD) grades 2–4 occurs in 15–60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2–4 in 60 pediatric patients. The cumulative incidence of aGvHD 2–4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2–4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3–191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2–4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06–3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.

Objective: Appropriate treatment for scorpion-associated pain was not previously studied in detail in the literature. The aim of this study was to compare the efficacy of three treatment modalities in patients with painful scorpion stings using visual analog scale (VAS) scores. Materials and Methods: A randomized study was carried out during a 1-year period in patients with scorpion stings who did not have any systemic signs or symptoms. Patients were treated with intravenous paracetamol, topical lidocaine, or ice application. Pain intensity was evaluated using VAS score at the time of presentation to emergency department and at 30th, 60th, 120th, and 240th minutes. Changes in VAS scores from baseline were recorded. Results: A total of 130 patients were included in the statistical analysis. Significant reduction in pain intensity was observed with topical lidocaine group when compared with the ice application group (p < 0.001) and paracetamol group (p < 0.001) in all selected time intervals. The median reduction in scores at 30 min after therapeutic intervention was 25.0 mm for topical lidocaine, 14.5 mm for ice application, and 10.0 mm for intravenous paracetamol. No adverse events were reported. Discussion: Our results revealed that topical lidocaine is superior to both intravenous paracetamol and local ice application and its effect lasts several hours after envenomation. conclusion: Topical lidocaine is an effective and safe treatment in scorpion sting associated with pain in patients with nonsystemic signs and symptoms.

The new coronavirus SARS-CoV-2 has rapidly spread over the world causing the disease by WHO called COVID-19. This pandemic poses unprecedented stress on the health care system including programs performing allogeneic and autologous hematopoietic cell transplantation (HCT) and cellular therapy such as with CAR T cells. Risk factors for severe disease include age and predisposing conditions such as cancer. The true impact on stem cell transplant and CAR T-cell recipients in unknown. The European Society for Blood and Marrow Transplantation (EBMT) has therefore developed recommendations for transplant programs and physicians caring for these patients. These guidelines were developed by experts from the Infectious Diseases Working Party and have been endorsed by EBMT’s scientific council and board. This work intends to provide guidelines for transplant centers, management of transplant candidates and recipients, and donor issues until the COVID-19 pandemic has passed.

Malignant infantile osteopetrosis (MIOP) is a rare hereditary disorder of osteoclast function, which can be reversed by hematopoietic stem cell transplantation (SCT). We observed a high incidence of hepatic veno-occlusive disease (VOD) in transplanted patients and explored the prevention of this complication by using defibrotide (DF) as a prophylaxis. Twenty children with MIOP were consecutively transplanted in our center between 1996 and 2005. Eleven of these patients were transplanted between 1996 and 2001 and experienced an overall incidence of VOD of 63.6% (7/11). VOD was severe in three patients and one patient succumbed to VOD-related multi-organ failure. Owing to this very high incidence of VOD, DF prophylaxis was initiated in nine patients consecutively transplanted between 2001 and 2005. In this group, only one patient (11.1%) was diagnosed with moderate VOD. We report here a very high risk in patients with MIOP to develop VOD after transplantation. Prophylactic DF was implemented in our current transplant protocol and reduced the VOD rate significantly in this high-risk population.