Background: GATA2-related myelodysplastic syndrome (GATA2-MDS) is a unique predisposition syndrome with a high risk of leukemic transformation. This systematic review synthesizes current literature and presents two illustrative pediatric GATA2-MDS cases. Methods: Data retrieval from eight cohort and case–control studies provides comprehensive analysis on disease features, diagnostic complexities, management, and outcomes related to hematopoietic stem cell transplantation (HSCT) in GATA2-related myeloid malignancies. Additionally, two pediatric cases are included to exemplify clinical and therapeutic challenges in real-world setting. Results: The literature data demonstrates high incidence of monosomy 7, and recurrent infections as the most common clinical feature, followed by immunodeficiency and lymphedema. Prognosis clearly worsens with age and HSCT remains the only curative treatment. GATA2 patients undergoing HSCT experience high rates of graft versus host disease (GvHD) as well as unique neurological, thrombotic, and infectious complications. Transplant-related mortality (TRM) is linked to GvHD and infections. Post-transplant cyclophosphamide (PT/Cy) strategies seem to improve survival by reducing GvHD incidence. Overall survival (OS) remains variable across groups. The first case presents rapid disease progression to pulmonary alveolar proteinosis (PAP) and leukemic transformation, further developing severe HSCT complications. The second case addresses novel GATA2 mutation and raises concerns regarding alternative prophylactic and therapeutic strategies in transplant setting. Conclusions: Collaborative efforts aim to enhance understandings of GATA2-related myeloid malignancies and guide towards more effective management approaches.

Background and Objectives: Due to the progress made in all areas of research, pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) now have an average overall survival rate of 90%. There are still discrepancies between high-income countries and limited-resource centers. The aim of this study was to analyze prognostic factors and outcome parameters in a 223-patient cohort from a single center in Romania, treated with two adapted BFM protocols. Materials and Methods: The patients diagnosed with ALL in our center were enrolled in this study from January 2016 to December 2022 and subsequently followed up until December 2024. The patients were treated first according to the ALL IC BFM 2009 protocol until June 2019 and afterwards with the ALL AIEOP BFM 2017 protocol starting with July 2019. The prognostic factors were analyzed in both subgroups and the outcomes were measured: event-free survival (EFS), overall survival (OS), cumulative incidence of relapse (CIR), relapse-free survival (RFS) and non-relapse mortality (NRM). Results: The comparison between the two subgroups revealed that every parameter improved over time: complete remission after induction (87.75% vs. 80.7%), early deaths (3.92% vs. 5.78%), deaths in remission (4.08% vs. 5.26%), 5-year EFS (73.79% vs. 70.22%), 5-year CIR (18.36% vs. 19.04%), 5-year RFS (81.76% vs. 80.97%), 5-year NRM (7.85% vs. 10.77%), and 5-year OS (88.18% vs. 82.54%). Whereas for the standard-risk group, events such as relapse or death were isolated, for intermediate-risk patients, the events were limited to a small number and did not significantly influence the overall results, and for high-risk children, the results improved significantly between the two subgroups. The worst outcomes were observed in patients with the BCR::ABL1 fusion gene, T-cell phenotype, and in teenagers, compared to the ETV6::RUNX1 fusion gene, B precursor ALL, and in smaller children, respectively. Conclusions: The 5-year OS increased in our center from 82.54% to almost 90%, with the most substantial finding being the survival rate for high-risk patients, now reaching up to 80%. The prognostic factors were age at diagnosis, genetic characteristics, and response to treatment, especially prednisone sensibility.

Background: MYH9-related disease (MYH9-RD) is the most common form of inherited thrombocytopenia (IT). It is caused by pathogenic variants in the MYH9 gene. It manifests as early-onset macrothrombocytopenia with variable later-onset extra-hematological features, including hearing loss, renal disease, and cataracts. In pediatric patients, early recognition is critical to avoid misdiagnosis as immune thrombocytopenia (ITP) and unnecessary immunosuppressive therapy. Methods: We conducted a retrospective unicentric study at the Pediatric Oncology and Hematology Department, Fundeni Clinical Institute, Bucharest, Romania, including patients aged 0–18 years with suspected IT, tested between 2017 and 2025 by next-generation sequencing (NGS). Clinical, laboratory, and genetic data were reviewed. Results: Among 66 patients who underwent genetic testing, 31 (48.5%) had IT-associated genetic variants; 8 (25.8%) carried MYH9 mutations. Four patients (50%) had disease onset before age 1 year, three with neonatal presentation; 3 (37.5%) reported a family history of thrombocytopenia. Six variants were previously reported, and two were novel variants. Five variants (62.5%) were pathogenic, while three (37.5%) were initially classified as variants of uncertain significance (VUS). Most mutations were missense in the coiled-coil tail domain, correlating with milder thrombocytopenia and absence of extra-hematological features. No life-threatening bleeding was recorded; hemorrhagic symptoms were limited to minor mucocutaneous bleeding. Conclusions: This is the first Romanian pediatric cohort and one of the few existing pediatric cohorts describing the genetic and clinical spectrum of MYH9-RD. Early genetic confirmation enables precise diagnosis, tailored management, and family screening, while preventing inappropriate therapies.

Acute lymphoblastic leukemia (ALL) is among the most curable pediatric cancers, yet relapse involving the central nervous system (CNS) remains a major therapeutic obstacle. In this prospective cohort, 97 children (aged 1.1-18.2 years) experiencing their first CNS relapse were enrolled in the ALL-IC REL study. Relapses were classified as isolated CNS (i-CNS, n = 43) or combined CNS (c-CNS, n = 54), and patients received treatment through standard- or high-risk regimens, encompassing chemotherapy, cranial irradiation, and allogeneic stem cell transplantation. The estimated 2-year event-free survival was 40.0%, and overall survival 49.4%, closely matching outcomes reported internationally. Survival rates were comparable across i-CNS and c-CNS relapses, while induction failure occurred more frequently in c-CNS. Multivariable analysis identified female sex, T-cell phenotype, and very early relapse as independent predictors of poor prognosis. These results underscore the critical necessity for risk-adapted therapy techniques and the incorporation of innovative medicines into forthcoming procedures.

Background/Objectives: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare but life-threatening thrombotic microangiopathy in children. Secondary forms, occurring in association with immune dysregulation, autoimmune disease, or other triggers, are particularly challenging to diagnose and manage, and pediatric-specific data remain limited. This study aimed to describe the clinical characteristics, diagnostic pathways, and management of pediatric iTTP and to contextualize these findings within the recent literature. Methods: We conducted a retrospective case series of pediatric patients diagnosed with iTTP at a tertiary referral center, between November 2021 and January 2026. Clinical presentation, laboratory findings, including ADAMTS13 activity and ADAMTS13 inhibitors, associated conditions, treatment strategies, and outcomes were reviewed. In parallel, a narrative literature review was performed focusing on pediatric immune-mediated secondary TTP published over the past five years. Results: Four pediatric patients (three females, one male; median age 14 years) met inclusion criteria. All presented with severe thrombocytopenia and microangiopathic hemolytic anemia, accompanied by prominent neurologic manifestations in three cases. Severe ADAMTS13 activity deficiency (≤10%) with positive inhibitors was documented in all patients. Secondary iTTP occurred in association with evolving systemic autoimmunity, systemic lupus erythematosus, common variable immunodeficiency, or without an identifiable trigger at presentation. High clinical probability scores facilitated early diagnosis. Management required plasma exchange, corticosteroids, and targeted and immunomodulatory therapy. Conclusions: Pediatric secondary iTTP is a heterogeneous condition that frequently presents with diagnostic ambiguity and severe neurologic involvement. Early recognition, prompt initiation of TTP-directed therapy, and comprehensive immunologic evaluation are critical for favorable outcomes. Case series combined with narrative reviews remain valuable for advancing understanding and optimizing individualized care in this rare pediatric disorder.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and genomic profiling has become increasingly vital for risk stratification. We conducted a retrospective single-center study including 96 newly diagnosed pediatric patients with ALL and mixed phenotype acute leukemia to characterize the genomic landscape using conventional and molecular cytogenetics, multiplex ligation-dependent probe amplification and targeted next-generation sequencing and to evaluate associations with treatment response and survival. Mutation co-occurrence analysis revealed a NRAS/KRAS/JAK cluster and an ETV6::RUNX1 cluster characterized by relative mutational exclusivity, with additional associations between NOTCH1–CDK4 and CDK4–CCND3 alterations. DelCDKN2A/CDKN2B alterations showed a trend toward higher day-15 minimal residual disease (MRD) levels and inferior 2-year event free survival rate (EFS). DelIKZF1-positive cases showed lower 2-year EFS. In contrast, ETV6::RUNX1 and high hyperdiploidy were associated with favorable early response and EFS. DelPAX5 did not independently influence outcome. ZNF384 positive cases showed higher early MRD levels despite excellent survival outcomes. NRAS/KRAS mutations were significantly associated with higher positive day-15 MRD (Wilcoxon, p = 0.0067) and remained independently associated after adjustment for white blood cell count and cytogenetic subgroup. Intermediate risk (IR) and high-risk groups showed comparable 2-year EFS, indicating limited discrimination by conventional risk stratification. The IR group displayed a heterogeneous genomic profile, with NRAS/KRAS, Ph-like mutations and delCDKN2A/CDKN2B among the most frequent alterations. These observations highlight the potential of integrated genomic profiling to refine risk stratification, particularly by identifying clinically relevant subgroups within the IR category.