Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged.

Data on treosulfan-based conditioning regimens are little by little increasing, and the benefits of this approach are consistent, particularly regarding acute toxicity. This study aims to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and non-malignant diseases. Retrospective observational study on pediatric patients treated in Spain with treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT), based on data collection from electronic clinical records. One hundred and sixty treosulfan-based conditioning HSCTs to treat non-malignant diseases (n=117) or malignant diseases (n=43) in 158 children and adolescents are reported. Median age at HSCT was 5.1 years (IQR: 2-10). The most frequent diagnoses were primary immunodeficiency (n=42; 36%) and sickle cell disease (n=42; 36%) in the non-malignant cohort and acute lymphoblastic leukemia (n=15; 35%) in the malignant cohort. Engraftment occurred in 97% of the patients. There was a longer median time to neutrophil engraftment (17 vs. 14 days; p=0.008) and platelet engraftment (20 vs. 15 days; p=0.002) in the non-malignant cohort. The 1-year cumulative incidence of VOD was 7.98 (95%CI [4.6-13.6]), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV aGvHD was higher in the malignant cohort (18% vs. 3.2%; p=0.011). Overall, cGvHD was more frequently observed in the malignant cohort for both total incidence (9 vs. 3%; p<0.001) and 2-year cumulative incidence of total cGvHD (16 vs. 1.9%; p<0.001). The 2-year cumulative TRM was 15%, with no differences between cohorts. 5-year Overall Survival was 80% (95%CI [72-86]) and was higher in the non-malignant cohort (87 vs. 61%; p=0.01). The 2-year cumulative incidence of relapse in the malignant cohort was 25%. 5-year cumulative GRFS rate was 60% (95%CI [51-70]) and was higher in the non-malignant cohort (72 vs. 22%; p<0.001). The treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival. A treosulfan-based conditioning regimen is an emerging option for the first HSCT in non-malignant diseases.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for malignant and non-malignant diseases; however, primary graft failure (GF) is a life-threatening complication, particularly with the increasing use of alternative donors and reduced-intensity conditioning (RIC) strategies. Data on outcomes and optimal management-especially in the pediatric population-remain limited and heterogeneous. The primary endpoint was overall survival (OS) in patients with primary GF. Secondary endpoints included OS in patients with primary GF after salvage HSCT and the evaluation of risk factors associated with engraftment and survival. We conducted a multicenter, retrospective, observational study including pediatric patients (<18 years) diagnosed with primary GF after a first allogeneic HSCT between January 2011 and July 2022 across 10 Spanish pediatric transplant centers. A total of 1561 allogeneic HSCTs were performed. Fifty-seven patients developed primary GF, yielding an overall incidence of 3.65%, which was higher among transplants with donors with HLA disparities. One-year OS for patients with primary GF was 73%. Over 90% of patients underwent salvage HSCT, with 74% achieving engraftment. No risk factors for engraftment were identified. One-year OS after the second HSCT was 71%. Achieving engraftment after the second transplant was the only factor significantly associated with survival (1-year OS, 81% [95% CI, 65-90] vs. 43% [95% CI, 17-66]; p < 0.001). No other clinical or transplant-related variables showed significant associations with survival. GF remains a major challenge and continues to limit the overall success of HSCT. The majority of patients underwent a second transplant, with engraftment achieved in 74% of patients. Overall survival was 68% at 2 years after the first transplant. The frequent use of RIC regimens including fludarabine and serotherapy in patients undergoing retransplantation reflects a commonly adopted clinical practice, although no specific conditioning regimen was significantly associated with engraftment or survival.