Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate the clinical response rates in both pediatric and adult patients with acute (a) or chronic (c) GVHD and to assess the effectiveness of ECP using the real-world data from a single center. Methods: We performed a retrospective study on 30 patients, including 11 pediatric and 19 adult patients who were treated with ECP as a second-, third-, or fourth-line therapy for (a) and (c) GVHD, alongside corticosteroids and other immunomodulatory medications. The median time from aGVHD onset to ECP was 11.5 days (range: 3 days–9 months), while for cGVHD, the median time was 90 days (range: 2 days–9 months). Results: The overall response rate (ORR) in the aGVHD patient population was 60% with a median of 9 procedures (range: 2–20). For cGVHD patients, the ORR was 70% after a median of 23.5 ECP procedures (range: 8–43). Most patients had skin involvement, with ECP achieving an ORR of 81.8% in aGVHD and 77.7% in cGVHD cases. Conclusions: ECP is a beneficial therapy for patients with (a) and (c) GVHD who have not responded to corticosteroids and other forms of immunosuppressive therapy. Specifically, ECP demonstrated efficacy in improving skin and oral symptoms and permitted reductions in or the elimination of their corticosteroid usage. The study found that extending the duration of ECP treatment was associated with better outcomes, and no detectable complications were observed over a 38-week period.

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.

Introduction: Donor lymphocyte infusion (DLI) can enhance graft-versus-leukemia (GvL) effects following allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). However, the optimal integration of azacitidine (Aza) with DLI in children remains uncertain. Methods: We retrospectively analyzed 16 pediatric AML patients (≤18 years) treated at Fundeni Clinical Institute between 2016 and 2024 who received DLI in combination with azacitidine (75 mg/m ² /day for 7 days every 4 weeks) after HSCT. DLI was administered prophylactically or preemptively based on mixed donor chimerism (MDC), measurable residual disease (MRD) positivity, or high-risk cytogenetics, or therapeutically for post-transplant relapse, with or without chemotherapy. Outcomes assessed included overall survival (OS), donor chimerism, relapse rate, and graft-versus-host disease (GVHD). Results: After a median follow-up of 46.5 months, five patients received prophylactic/preemptive DLI and eleven received therapeutic DLI (seven with chemotherapy, four without). All patients in the prophylactic/preemptive group achieved full donor chimerism and MRD negativity, with an OS of 80% at 2.7 years. In the therapeutic group, median OS was 23.8 months with chemotherapy and 13.8 months without. OS differences between groups were not statistically significant (p = 0.384). Acute GVHD occurred in two patients (12.5%) in the therapeutic + chemotherapy subgroup; no chronic GVHD or non-relapse mortality was observed. Conclusion: Azacitidine combined with DLI is feasible and safe in pediatric AML after HSCT, particularly when applied prophylactically or preemptively to restore donor chimerism or eradicate MRD. Therapeutic use in overt relapse remains challenging and provides limited benefit. Prospective multicenter studies are needed to define optimal timing, dosing, and combination strategies for integrating azacitidine with DLI in this high-risk pediatric population.

Introduction: Optimal conditioning regimen for pediatric myeloid malignancies is still subject for debate. This single-center retrospective study compares the efficacy and toxicity profiles of three conditioning strategies, myeloablative conditioning (MAC), reduced-toxicity conditioning (RTC), and reduced-intensity conditioning (RIC), in 59 pediatric patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT).Methods: Primary objectives evaluated graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS), and mortality causes. Secondary endpoints assessed early complications such as mucositis, engraftment kinetics, viral reactivation, and hospitalization duration. A subgroup analysis compared fludarabine- and clofarabine-based RTC regimens.Results: RTC was associated with significantly lower transfusion needs, faster platelet engraftment and shorter hospitalization. Viral reactivations were more common in RTC and RIC, yet viral control, particularly CMV clearance, seemed more effective in RTC. While one-year OS and DFS were generally comparable across regimens, RTC showed a numerically higher OS, with a possible negative influence on relapse rate for children under 10 years old. Severe acute GvHD was similar across groups, but chronic GvHD tended to occur more frequently in RIC. CR status appeared to influence relapse and mortality patterns, with AML patients transplanted in CR1 experiencing significantly better OS and DFS. Subgroup analysis within RTC (clofarabine vs. fludarabine) revealed promising trends toward improved OS, lower acute GvHD, and reduced relapse-related mortality when using clofarabine.Discussions: These findings support the use of individualized conditioning strategies in pediatric myeloid malignancies, with RTC emerging as a potentially balanced approach for selected cases.

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.