Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10–15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.

Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7–12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015–2022 (two induction cycles followed by stem cell transplantation—SCT in 69% of patients) compared to 2005–2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015–2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.

Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) type I and II is a rare and life-threatening disease caused by SERPING1 gene mutations. Previous genetic studies indicated a wide spectrum of disease-associated variants in the SERPING1 gene and often lack of correlation with patient’s phenotypes. The aim of this study was to evaluate the presence, type, and localization of mutations in the SERPING1 gene in 41 Polish patients with C1-INH-HAE and their relation with case/family history, type of C1-INH-HAE, fC1-INH, age of onset, and disease severity. Sanger sequencing and MLPA method were used for detection of disease-associated variants. In 34 (82.9%) patients, mutations located in various regions of SERPING1 gene were revealed. The detected alterations in patients with C1-INH-HAE type I differed and were positioned in various exons/introns of the SERPING1 gene. The most frequent disease-associated variants appeared in exon 3 (especially in type I) and in exon 8 (type I and II). Out of 20 different disease-causing variants, 9 were not previously described. We did not find any relation between the type and location of the mutations and no type of features included in phenotype evaluation of the patients, such as case and family history, type of C1-INH-HAE, age of onset, biochemical parameters, or severity of disease.

Background: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. Patients and Methods: We retrospectively analyzed 220 AML patients aged 0–18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1–9.9 years), 59 older children (10–14.9 years), and 39 adolescents (15–18 years). Results: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1–3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/μL [HR, 2.4 (95% CI 1.3–4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. Conclusions: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.

Measurable residual disease (MRD) is a well-known tool for the evaluation of the early response to treatment in patients with acute lymphoblastic leukemia (ALL). In respect to predicting the relapse the most informative cut-off and time point of MRD measurement during therapy were evaluated in our study. Between 1 January 2013 and 31 December 2019, multiparametric flow cytometry (MFC) MRD was measured in the bone marrow of 140 children with ALL treated according to the ALL IC-BFM2009 protocol. The MRD cut-off of 0.1% and day 33, end of induction, were the most discriminatory for all patients. Patients with negative MRD on day 15 and 33 had a higher 5-year overall survival—OS (100%) and a higher relapse-free survival—RFS rate (97.6%) than those with positive levels of MRD (≥0.01%) at both time points (77.8% and 55.6%, p = 0.002 and 0.001, respectively). Most patients with residual disease below 0.1% on day 15 exhibit hyperdiploidy or ETV6-RUNX1 in ALL cells. Measurement of MRD at early time points can be used with simplified genetic analysis to better identify low and high-risk patients, allowing personalized therapies and further improvement in outcomes in pediatric ALL.

Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature. Case presentation: We report two pediatric patients harboring pathogenic ACAN gene variants, both presenting with short stature and distinctive facial dysmorphism. The first patient, a 15-year-old boy, exhibited short stature, advanced bone age, and a characteristic facial gestalt, including ptosis, hypertelorism, down-slanting palpebral fissures, and fleshy auricles, features not previously described in association with aggrecanopathy. Genetic analysis revealed a novel heterozygous frameshift variant, c.5677_5684del (p.Glu1893TrpfsTer8), in exon 12 of the ACAN gene. The second patient, a 5.5-year-old girl, presented with short stature, mild facial dysmorphism (down-slanting palpebral fissures and retracted mandible), and feeding difficulties. Copy number variation analysis identified a heterozygous deletion encompassing exons 15–19 of the ACAN gene. In both patients, the endocrine evaluation was unremarkable, and no chronic systemic disease was identified. The genetic findings were concordant with the clinical phenotype, confirming aggrecanopathy as the underlying cause of growth failure. Conclusions: These cases further delineate the phenotypic spectrum of ACAN-related short stature and underscore the diagnostic value of genetic testing in children with unexplained or idiopathic growth failure. Importantly, we expand the dysmorphological phenotype of aggrecanopathy by describing previously unreported facial features, which may facilitate earlier clinical recognition and diagnosis. The timely identification of pathogenic variants in the ACAN gene may have significant implications for patient management and long-term outcomes.