Central neurotoxicity as a complication in course of treatment of acute lymphoblastic leukemia in children: a single center experience

Introduction: Neurotoxicity is a common and severe complication of the treatment of acute lymphoblastic leukemia in children, and affects 10–15% of patients. The aim of this study was to show the characteristics of this group over the course of time, the outcomes of patients, and to evaluate possible clinical risk factors for central nervous system toxicity. Material and methods: Clinical data from patients hospitalized between 2003 and 2018 was obtained from hospital records and assessed retrospectively. Additional data was obtained to characterize the group of neurotoxic events. Statistical analysis was used to describe study group and intragroup associations, as well as event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS). The cohort comprised 224 patients (median age 5.64 years), consisting of 130 boys (58%) and 94 girls. 129 of tchem were treated with Protocol ALLIC BFM 2002 (57.6%), and 95 with Protocol ALLIC BFM 2009. Results: Twenty-one patients (9.37%) developed subacute central neurotoxicity, which comprised posterior reversible encephalopathy syndrome, stroke-like syndrome and seizures, defined according to the Ponte di Legno working croup criteria. The 5-year OS and EFS of the analyzed group were 85.11% [95% confidence interval (CI): 8.32–89.82%] and 80.03% (95% CI: 74.69–85.38%) respectively. There was a statistically significant difference in EFS and RFS between neurotoxic and non-neurotoxic patients (p = 0.00082 and p < 10–5 respectively), but this did not affect overall survival (p = 0.10). In multivariate analysis, the risks of death, adverse events and relapses were increased in patients belonging to the neurotoxicity group [hazard ratio (HR) 3.18, 95% CI: 1.26–8.06, HR 4.96, 95% CI: 2.4–10.22, HR 7.22 95% CI: 3.21–16.24, respectively). Conclusion: The occurrence of neurotoxicity might be associated with poorer prognosis among pediatric patients with ALL

Hematological toxicity of mTOR inhibitors is mild and dose-dependent in patients with tuberous sclerosis and subependymal giant cell astrocytoma

Introduction: Everolimus is the primary therapeutic option for patients with tuberous sclerosis complex (TSC) and subependymal giant astrocytoma (SEGA). This study aimed to assess the effect of everolimus, a mammalian-target-of-rapamycin (mTOR) inhibitor, on complete blood count (CBC) parameters in patients with TSC and SEGA. Material and methods: The study included 18 pediatric patients with TSC-associated SEGA tumors as indications for everolimus treatment. During the standard dose therapy and maintenance phase (<50% of standard dose), CBC results and everolimus whole blood concentrations were collected at five study time points. Results: Everolimus contributed to decreasing almost all blood cell values. The most severe toxicity occurred six months after therapy commenced. Dose reduction resulted in slightly normalizing parameters, but they did not return to the initial ones in all cases. During the study, only a few instances of cytopenia were reported. The most common abnormality was granulocytopenia, observed in one in three patients. Almost all cytopenias occurred during the standard treatment phase, and none were classified as severe. Hematological toxicity was not the reason for therapy interruption or withdrawal. Conclusions:A decrease in almost all hematological parameters is widespread during everolimus therapy. Hematological toxicities are rare and mild. The unique abnormality for mTOR inhibitors is microcytosis. Reduction of mTOR inhibitor dose results in a lower frequency of hematological side effects

Challenges of biological therapy in patients with pustular psoriasis coexisting with psoriatic arthritis

Introduction . Psoriasis is a chronic inflammatory skin disease affecting approximately 2–3% of the general population. It is a condition with immunological and genetic background, coexisting with psoriatic arthritis in about 25% of cases. Biologic drugs have brought a significant improvement in managing the disease, however they are not approved for the treatment of pustular psoriasis. An increasing number of reports indicate the efficacy of biological drugs in pustular psoriasis. In some patients there are factors responsible for a worse clinical response to biologic therapy. Objective . Presentation of therapeutic difficulties identified in a patient with pustular psoriasis and psoriatic arthritis. Case report . We report a case of a 48-year-old man with generalized pustular psoriasis coexisting with psoriatic arthritis in whom therapy with multiple biologic drugs (adalimumab, infliximab, golimumab, ustekinumab) has failed to bring a satisfactory improvement. Conclusions . Further studies are needed to verify the efficacy and pos­sibly approve biological drugs for the treatment of pustular psoriasis. Also, attempts should be made to identify predictors of poorer response to treatment in order to individualize therapy and prevent the loss of efficacy of biologic drugs during prolonged use

One Hundred Consecutive Neutropenic Febrile Episodes Demonstrate That CXCR3 Ligands Have Predictive Value in Discriminating the Severity of Infection in Children with Cancer

This study assesses the value of the CXCR3 ligands CXCL9/MIG, CXCL10/IP-10 and CXCL11/I-TAC when used to supplement the standard infection markers C-reactive protein (CRP) and procalcitonin (PCT) in the diagnostic algorithm of neutropenic fever in children with cancer. The concentration of CRP, PCT and chemokines was determined during the first hour of fever and 12–24 h afterwards in pediatric oncology patients with neutropenia. Among 100 consecutive febrile episodes in neutropenic patients, 34 cases demonstrated fever of unknown origin (FUO) (group A), 47 demonstrated mild clinically or microbiologically proven infection (Group B) and 19 severe infection (Group C). Significantly higher PCT-1 levels were found in group C (0.24 ng/mL) vs. group A (0.16 ng/mL), and PCT-2 in group C (1.2 ng/mL) vs. A (0.17 ng/mL), and in C vs. B (0.2 ng/mL). Chemokine concentrations (I-TAC-1, IP-10-1, IP-10-2) were significantly lower in Group A vs. B+C; I-TAC 1: 48.64 vs. 70.99 pg/mL, p = 0.03; IP-10 1: 59.95 vs. 96.84 pg/mL, p = 0.04; and IP-10 2: 102.40 vs. 149.39 pg/mL, p = 0.05. The selected pro-inflammatory chemokines I-TAC and IP10 might help to distinguish cancer patients with febrile neutropenia with the highest risk of infection. Although procalcitonin could serve as a marker of a high risk of infection, its delayed response diminishes its usefulness