Journal of Pediatric Hematology/Oncology最新文献

We report a case of a 17-year-old male presenting with acute compartment syndrome (CS) of the lower extremity as the initial manifestation of CRLF2-positive, Ph-like B-cell acute lymphoblastic leukemia (B-ALL), without evidence of leukemic infiltration or hematoma. Emergent fasciotomy was performed, followed by cytoreduction with hydroxyurea to allow wound healing before induction chemotherapy. The patient fully recovered and completed induction without complications. This case highlights the importance of recognizing CS as a rare presenting feature of leukemia, and supports hydroxyurea bridging as a viable strategy when immediate chemotherapy is contraindicated to support surgical recovery.

Introduction: Ewing Sarcoma (ES) is a small, round, blue cell tumor (SRBCT) characterized by a chromosomal translocation between chromosomes 11 and 22 in ~85% of cases, alongside immunohistochemical (IHC) expression of the surface glycoprotein CD99. Despite advancements in molecular diagnostics, low-income countries continue to face challenges in tumor classification and identification of fusion partners.

Methods: This study retrospectively analyzed pathology reports from 396 patients enrolled in the Latin American Cooperative Group (GALOP) trial, with data collected until December 2021. CD99 positivity or molecular confirmation of EWSR1 translocation were required for inclusion.

Results: IHC marker selection varied across pathology units, reflecting differences in national guidelines. FLI1 was assessed in 45.5% of cases, VIM in 40.4%, and NKX2-2 in 14.9%. The most common complementary markers included desmin (60.1%), myogenin (47.5%), LCA/CD45 (51.5%), and synaptophysin (44.9%). EWSR1 translocation confirmation was performed in 74 patients (18.6%) using FISH and/or PCR. Molecular testing was more frequent in Argentina (73%), while Brazil, Chile, and Uruguay reserved it for diagnostically uncertain cases. Ki-67 was assessed in 70 cases, with most showing a high proliferation index (>30%).

Conclusion: These findings underscore the need for continued collaboration to standardize diagnostic approaches across Latin America, aiming to improve treatment outcomes for ES patients.

Aim: Hematopoietic stem cell transplant (HSCT) remains the cornerstone of treatment in patients with high-risk and relapsed acute myeloid leukemia (AML). In the absence of a fully matched donor, haploidentical HSCT is a feasible option. The aim of this study is to analyze the outcomes of pediatric AML patients, who underwent HSCT at our center.

Methods: This was a retrospective analysis of 48 pediatric patients who underwent 50 transplants at our center from January 2014 to December 2024.

Results: Median age at transplant was 8.5 years, and the male-to-female ratio was 1.9:1. Of 48 children, 46 patients had de novo AML, and 2 had secondary AML. Twenty-nine patients underwent matched sibling donor (MSD), 3 underwent matched related donor (MRD) and the remaining 18 received haploidentical HSCT. All patients received Fludarabine-based conditioning regimens and engrafted. Incidence of acute graft versus host disease (GVHD) in matched donor and haploidentical HSCT was 21.8% and 44.4%, respectively ( P =0.09). Incidence of chronic GVHD was 3.1% in matched donor and 5.5% in haploidentical HSCT ( P =0.72). Cumulative incidence of relapse was 16%. Viral reactivations were seen in 17 patients, cytomegalovirus (CMV) being the commonest. At a median follow-up of 40.9 months, EFS and OS of the overall cohort were 78% and 86%, respectively. Nonrelapse mortality (NRM) was 6%. EFS in matched donor and haploidentical HSCT was 78.1% versus 77.8% ( P =0.78). OS in matched donor and haploidentical HSCT was 84.4% versus 88.9% ( P =0.83). GVHD-free relapse-free survival (GRFS) was 58%. Among the factors analyzed, only pretransplant minimal residual disease (MRD) positivity was found to be associated with significantly poor outcome.

Conclusion: HSCT for children with AML from the developing world shows promising outcomes with high survival rates even in the absence of matched donors. Having expertise in multiple specialties, such as a molecular hematologist, infectious disease (ID), and intensive care specialist, can significantly enhance the outcomes for transplant patients.

Background: GNE mutations are rare pathologic conditions that can cause severe thrombocytopenia and bleeding tendency from the neonatal period. The clinical presentation of patients with GNE mutations varies from mild skin and mucosal bleeding to life-threatening bleeding.

Case presentation: This study reported two siblings with hereditary thrombocytopenia. The 2 patients exhibited severe thrombocytopenia (platelet [PLT] count: <15,000/mm 3 ) since the neonatal period and did not respond to intravenous immunoglobulin (IVIG) and steroids. The patients required PLT transfusions once every 1 to 2 weeks due to frequent bleeding incidence. Whole-exome sequencing was performed based on the preliminary diagnosis of inherited thrombocytopenia. A homozygous missense variant (c.1675G>A [p.Gly559Arg]) was detected in GNE . One sibling was unresponsive to the platelet receptor agonists eltrombopag and romiplostim. Meanwhile, the other sibling was unresponsive to eltrombopag but was responsive to romiplostim.

Conclusion: The first-line treatment of patients with GNE mutations is PLT transfusion. However, the management of patients with severe thrombocytopenia and frequent bleeding is challenging. Thrombopoietin receptor agonists are administered to these patients to mitigate the risk of alloimmunization and PLT transfusion refractoriness. However, the observed responses may differ even in siblings carrying the same mutation. This differential response may be related to bone marrow megakaryocyte reserves and hepatocyte Aswell-Morell receptor levels.

Several international studies have reported qualitative alterations in the concentrations of specific trace elements among individuals diagnosed with leukemia. However, further investigations are required to validate these associations and better understand the observed elemental variations. In Karbala province, there is a lack of research addressing the distribution of trace elements in pediatric leukemia cases. The aim of this study was to evaluate the concentrations of selected trace elements (Cd, Pb, Co, Al, Cu) in the blood of children with leukemia in Karbala, and to determine whether these levels differ from the normal reference ranges reported by WHO and NIH guidelines, as well as between urban and rural populations. This study measured the concentrations of cadmium (Cd), lead (Pb), cobalt (Co), aluminum (Al), and copper (Cu) in blood samples collected from 20 children with leukemia at Al-Hussein Medical City Hospital. Atomic absorption spectroscopy (AAS), using both Flame and Graphite Furnace techniques, was used to quantify the levels. The observed concentrations were copper (46.192 to 274.866 ppb), lead (0.767 to 8.675 ppb), cobalt (0.331 to 3.170 ppb), cadmium (0.466 to 1.752 ppb), and aluminum (15.011 to 24.787 ppb). The results indicated that the concentrations of these trace elements were generally lower than the internationally recognized normal ranges. In addition, a geographic variation was observed: children residing in the urban center exhibited lower trace element concentrations compared with those living in rural areas.

Cartilage hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders are rare skeletal dysplasias caused by pathogenic variants in RMRP, associated with immune dysfunction and cancer predisposition. While non-Hodgkin lymphoma is more commonly seen, Hodgkin lymphoma (HL) is rarely reported, and its management in this setting remains unclear. We describe 2 siblings with genetically confirmed CHH-AD who developed relapsed/refractory EBV-positive classic HL. Both presented with short stature, atopy, recurrent infections, and elevated IgE. The brother was diagnosed with stage IV disease, and the sister with stage IIB. Despite receiving frontline chemotherapy, both relapsed within a year. Salvage therapy with gemcitabine/vinorelbine induced metabolic responses, followed by radiotherapy and consolidation with brentuximab vedotin. Autologous transplant was considered but declined by the family due to perceived risks. At 30 months follow-up, both remain in complete remission. Genetic testing confirmed a shared homozygous pathogenic RMRP variant. These cases expand the oncologic spectrum of CHH-AD to include HL, highlight the risk of aggressive disease and early relapse, and demonstrate that durable remission may be achieved without transplantation when consolidation with targeted therapy is feasible. Early recognition of CHH-AD features in HL patients may allow risk-adapted therapy and informed genetic counseling.

Hepatitis-associated aplastic anemia (HAAA) is a rare but potentially life-threatening form of acquired aplastic anemia. Since 2022, our center has observed an increase in HAAA cases. This study examines pediatric HAAA cases to enhance understanding of its presentation, diagnosis, and treatment outcomes, aiming to guide future research and care protocols. A retrospective review was conducted on 5 pediatric HAAA patients treated between 2022 and 2023 at a tertiary children's hospital in the Midwestern United States. Data included clinical presentation, diagnostics, bone marrow and liver pathology, treatments, and clinical course. Immunohistochemical analysis was performed on liver biopsies. As a result, none of the 5 patients developed liver failure. One patient had a genetic mutation associated with an immune-mediated disease; other genetic tests were negative. Histopathology revealed consistent CD8 T-cell infiltration in the liver and bone marrow, with a median CD4/CD8 ratio of 0.5. The median interval from hepatitis onset to pancytopenia was 7 to 9 weeks, with a median follow-up of 2.5 years. Four patients developed severe aplastic anemia (sAA), and 1 had nonsevere aplastic anemia (NSAA). Steroid therapy was insufficient in 4 cases, necessitating antithymocyte globulin (ATG) and cyclosporine. Due to nonresponse, 4 patients required stem cell transplantation (SCT). HAAA can rapidly progress to sAA, highlighting the importance of early, aggressive intervention. Equine ATG and cyclosporine should be initiated promptly, but refractory cases often require SCT. Further research is essential to refine therapeutic strategies and improve outcomes.

Ocular relapse in pediatric acute lymphoblastic leukemia (ALL) is rare and typically associated with central nervous system or bone marrow involvement. Anterior segment infiltration as the sole manifestation of relapse is exceptionally uncommon and may mimic noninfectious uveitis, leading to diagnostic delay. We report the case of a 4-year-old boy with a history of B-cell precursor ALL, diagnosed at age 2 and treated according to the ALL IC BFM 2009 protocol. The patient remained in remission until presenting with persistent redness and irritation of the left eye, unresponsive to topical corticosteroids and cycloplegics. Slit-lamp examination revealed sectoral iris thickening, which was further assessed using ultrasound biomicroscopy and confirmed localized stromal infiltration without ciliary body involvement. The posterior segment was unremarkable. Initial systemic reevaluation showed no evidence of hematologic or CNS relapse, and at that time, ocular findings were provisionally considered an isolated recurrence. However, ∼3 months after the onset of ocular symptoms, the patient exhibited hematologic abnormalities, and relapse was confirmed with 31% circulating blasts, thrombocytopenia, and 92% blasts in bone marrow aspirate. He was subsequently reclassified as high-risk and systemic therapy was resumed. This case illustrates a rare presentation of anterior segment involvement as the initial manifestation of relapse in pediatric ALL. Clinicians should maintain a high index of suspicion when evaluating persistent or atypical anterior uveitis in leukemia survivors, as early recognition of ocular involvement may be critical for timely diagnosis and treatment of systemic recurrence.

Hatipoglu immunodeficiency syndrome (HATIS) is an autosomal recessive immunologic disorder, characterized by cytopenias, recurrent infections, and failure to thrive associated with biallelic mutation in DPP9 gene. We report 8-month-old pair of twins born to a nonconsanguineous marriage with similar presentation showing severe anemia and recurrent sino-pulmonary infections requiring multiple hospitalizations and blood transfusions with investigations suggestive of macrocytic anemia unresponsive to B12 supplementation. Immunodeficiency workup showed positive Dihydrorhodamine test suggestive of chronic granulomatous disease and whole exome sequencing displayed DPP9 mutation in both the twins.