Background: Acute kidney injury (AKI) is a frequent and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite relatively high prevalence, AKI after allo-HSCT and its risk factors in children remain obscure. The aim of this study was to describe the prevalence and course of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with baseline characteristics. Methods: Retrospective single-center chart review of all patients under 18 who underwent allo-HSCT during 2011-2017 was performed. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Recurrent AKI and acute kidney disease (AKD) were defined according to the Acute Disease Quality Initiative consensus. Demographic, clinical, and procedure-related characteristics were recorded at the day of HSCT. Conclusions: AKI is a frequent early complication of allo-HSCT in children, and approximately one fifth experience AKI recurrence and one third develop AKD. Older age, higher BMI, and higher eGFR at the day of transplant may have an effect on the risk of AKI development and its course.

Introduction: Acute kidney injury (AKI) is a common and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous factors associated with allo-HSCT and primary disease itself, including use of nephrotoxic drugs, occurrence of complications, such as infections, graft-versus host disease and other, may play a role in developing AKI. Despite relatively high prevalence, the occurrence of AKI after allo-HSCT in children is scarcely described. The aim of our analysis was to describe the prevalence and characteristics of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with various baseline characteristics. Methods: Retrospective chart review of all pediatric patients who underwent allo-HSCT at Vilnius University Hospital Santaros Clinics during 2011-2017 was performed. Estimated glomerular filtration rate (eGFR) was calculated using serum creatinine based Schwartz equation. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Results: A total of 51 patients (68.6% boys) with a median age of nine years (IQR, 3.5-13) were included into the analysis. HSCT indication was hematological malignancy in 32 (62.8%) patients and 27 (52.9%) received myeloablative conditioning. During a median follow-up of 82 (IQR, 59.5-98) days, 27 (52.9%) patients experienced at least one AKI episode with a total of 53 AKI episodes throughout the follow-up. Median time to first AKI was 28 (IQR, 7-42) days. Multiple AKIs occurred in 13 (25.5%) patients: six, three, two and two patients had two, three, four and five AKI episodes, respectively. Early AKI reversal (in <48 hours) occurred in 30 (56.6%) of all AKI episodes. Short term renal replacement therapy was required during two AKI episodes. Three patients died during the first 100 days and all had previous or ongoing AKI. No differences in age, sex, preparative regimen, hematopoetic stem cell source, T-cell depletion, baseline body mass index, baseline eGFR or comorbidity were found when comparing patients with and without AKIs or multiple AKIs. However, patients with HSCT indications other than hematological malignancies had higher chance of experiencing multiple AKIs (OR 3.9, 95% CI [1.1, 15.7], p=0.042). Conclusions: Approximately half of children experience at least one stage I or higher AKI and one fourth experience multiple AKIs within 100 days after allo-HSCT. Children with diseases other than hematological malignancies have a higher chance of multiple AKIs. Baseline demographic, anthropometric and HSCT-related characteristics appear not to be associated with increased AKI risk.

Invasive fungal diseases (IFD) remain a major cause of morbidity and mortality in hematological patients, especially those undergoing hematopoietic stem cell transplantation (HSCT). Despite relatively high incidence, diagnosis and treatment remain a challenge due to non-specific manifestation and limited antifungal armamentarium. A first-in-class triterpenoid antifungal ibrexafungerp that acts by inhibiting the glucan synthase enzyme in the fungal cell wall was recently approved by the USA Food and Drug Administration for the treatment of vaginal yeast infections. Preclinical data show activity against numerous fungi species, including azole- and echinocandin-resistant strains. Preliminary data from ongoing phase 3 studies in IFD have been encouraging, but the role of ibrexafungerp in hematological patients who develop fungal infections has not yet been described. Herein, we discuss the feasibility of oral ibrexafungerp-based antifungal therapy for adult patients with hematological malignancies who have either undergone HSCT or received treatment with a novel targeted therapy agent. We present four clinical cases where ibrexafungerp alone or in combination with other antifungal agents was successfully employed for the management of refractory fungal infection. We describe real-life experiences showing the potential clinical implementation of ibrexafungerp for patients with hematological malignancies for the first time, and provoke future discussion.

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