Background. Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT) and associated with a high mortality rate. Therefore, accurate and immediate diagnosis is crucial for implementing appropriate treatment. Objectives. In our single-center retrospective study, we assessed the accuracy of the Modified Seattle Criteria in children and adolescents undergoing HSCT, and compared them to the diagnostic criteria recently established by the European Society for Blood and Marrow Transplantation (EBMT). Material and methods. Retrospective analysis of medical records of 951 HSCT procedures performed in 850 children and young adults in the years 2001-2015 in the Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation of Wroclaw Medical University Supraregional Center of Pediatric Oncology "Cape of Hope" in Wroclaw, Poland. Results. Among the 850 children, 48 were diagnosed with VOD according to the Modified Seattle Criteria (5.05%). Thirteen patients (27%) developed VOD later than within 20 days after transplantation, as required in the diagnostic criteria. Five of the 6 patients who died from VOD were diagnosed with late-onset VOD. Using the categories of symptoms described in the Modified Seattle Criteria, hepatomegaly and weight gain were the most common symptoms in the analyzed cohort (81.25% and 68.75%). Fourteen patients (29%) never demonstrated elevated plasma bilirubin level (>2 mg/dL), as suggested in the Modified Seattle Criteria. Twenty-nine patients (64%) had increased platelet consumption requiring daily transfusions. Only 5 patients with decreased plasma antithrombin III (ATIII) activity level (<80%) on the day of HSCT developed VOD despite supplementation of ATIII. Conclusions. The Modified Seattle Criteria seemed to not meet the special needs of the pediatric population. The new diagnostic criteria proposed by the EBMT appear to be more adequately tailored to the pediatric population and may significantly change the conception of VOD in the future. The surprisingly low incidence of VOD in our cohort may suggest a beneficial role of monitoring and early supplementation of ATIII.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wrocław during years 2016–2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41–0.95) vs. 1yrOS others = 0.96 (95% CI 0.89–0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients.

SOS/VOD is a life-threatening complication of hematopoietic stem cell transplantation, especially in children, with incidences reaching up to 15–20%. Despite efforts, SOS/VOD remains unpredictable with significant morbidity and mortality. High-risk criteria are clearly defined, and the pediatric EBMT diagnostic criteria have improved sensitivity, reducing treatment delays and enhancing outcomes. A meta-analysis combining retrospective and prospective studies found a risk ratio of 0.30 for SOS/VOD with defibrotide (DF) prophylaxis. Additionally, two prospective trials were conducted: the pediatric prevention trial (NCT00272948) and the Harmony Trial (NCT02851407), involving adults and children, with primary outcomes of incidence and SOS/VOD-free survival, respectively. The trials produced conflicting results regarding the effectiveness of prophylactic DF. Despite significant limitations of the Harmony trial, a direct healthcare professional communication (DHPC) from the European Medicines Agency (EMA) advised against prophylactic DF. This recommendation has serious consequences for children, especially infants, who are among the most vulnerable groups receiving HSCT. Therefore, a panel of experts issued guidelines for children at high risk for SOS/VOD, in which DF prophylaxis is considered justified. These guidelines include a weighted scoring system based on all relevant high-risk criteria to predict SOS/VOD, supporting decisions regarding the use of prophylactic DF in children.

Acute graft-versus-host disease (aGvHD) is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Identifying its risk factors would enable the proper prophylaxis and management, which may significantly improve the general outcome of children treated with HSCT. The aim of this single-center, retrospective cohort study was to assess the potential risk factors for grades II-IV of aGvHD in children after the 1st allo-HSCT from an unrelated donor (UD), performed as a result of an underlying malignant disease. From among patients who received HSCT in our center in the years 2004-2015, 237 were included in the study cohort. All the patients received standard aGvHD prophylaxis consisting of cyclosporine (CsA) and a short course of methotrexate (MTX). Various clinical and epidemiological features, the transplant proceedings, graft composition, conditioning regimens, as well as the duration and coherence of aGvHD prophylaxis were analyzed as potential risk factors for aGvHD. The incidence of II-IV aGvHD in the study cohort was 58.6%. The median time of the diagnosis of aGvHD was 18 days post-HSCT. In the multivariate analysis, risk factors significantly associated with grades II-IV of aGvHD were: myeloablative conditioning regimen containing total body irradiation (TBI-MAC) (RR (relative risk): 1.69; p = 0.03), premature termination of CsA administration due to its toxicity (RR: 1.99; p = 0.0003) and HSCT performed before the year 2009 (RR: 1.97; p = 0.0001). Donor and recipient age, donor-recipient sex mismatch, stem cell source, risk of disease, and amount of infused CD34+ cells seem to be insignificant as risk factors for aGvHD. The overall survival (OS) of patients with aGvHD was noticeably worse that in those who were aGvHD-free: 60.8% vs 74.1% (p = 0.08). The conditioning regimen and the proper aGvHD prophylaxis, including continuous CsA administration, have a major impact on aGvHD occurrence. According to our results, the termination of CsA therapy should be carefully considered, and avoided if possible.