Gyermekkori neuroblastoma kezelésében alkalmazott 131-I-meta-jodo-benzil-guanidin terápia. Első hazai tapasztalatok

Neuroblastoma, representing one-tenth of childhood malignancies, is a clinically and prognostically heterogeneous disease. Survival in cases with poor prognosis has recently been significantly improved by rapidly evolving multimodal therapy. Our 4-year-old patient presented with bitemporal swelling and the diagnostic workup confirmed stage IV neuroblastoma (bone marrow and multiple bone metastases). While the tumor responded well to the initial treatment, it relapsed during post-consolidation therapy. As part of the salvage therapy for this high-risk disease with poor prognosis, 131-I-meta-iodo-benzyl-guanidine treatment was performed for the first time in our country, in a case of pediatric neuroblastoma. Neuroendocrine tissue cells express a norepinephrine transporter capable of uptaking the catecholamine analog meta-iodo-benzyl-guanidine. This mechanism makes it an adequate molecule for the imaging (123-I-meta-iodo-benzyl-guanidine) and target therapy (131-I-meta-iodo-benzyl-guanidine) of neuroendocrine tumors, including neuroblastoma. Treatment with 131-I-meta-iodo-benzyl-guanidine requires specific personnel and infrastructural equipment, particularly in pediatric cases. Careful organization and cooperation between nuclear medicine specialists and collaborating clinicians (pediatric oncologists and adult internists if necessary) are essential. Meta-iodo-benzyl-guanidine therapy, already routinely used abroad, has been considered as part of salvage therapy for recurrent neuroblastoma until now, but ongoing clinical trials suggest that it may become part of the first-line treatment soon. As the indications broaden, it is necessary to make it available for more and more children in our country. Orv Hetil. 2023; 164(39): 1550-1555

Primer nyaki lymphadenopathia formájában jelentkező, IgG4-hez társult betegség gyermekkorban = IgG4-related disease manifesting in the form of primary cervical lymphadenopathy

A nyaki nyirokcsomó-megnagyobbodás gyakori jelenség gyermekkorban. A benignus, átmeneti kórképek mellett a tünetek hátterében súlyos kórállapotok is állhatnak. A szerzők egy 12 éves fiúgyermek esetét mutatják be, aki több hónapja fennálló, progrediáló nyaki nyirokcsomó-megnagyobbodás miatt került klinikai felvételre. A laboratóriumi vizsgálatok malignitásra nem utaltak, a pontos etiológia tisztázása céljából biopsziás mintavétel történt. A szövettani vizsgálat immunglobulin-G4-hez (IgG4) társult betegséget mutatott. A szövettani vizsgálati eredményt a kórképre jellegzetes laboratóriumi eredmények, illetve a jellegzetes bőrfolyamat is alátámasztotta. Egyéb szervi manifesztáció kizárására pozitronemissziós tomográfiás (18FDG-PET/CT), illetve hasi mágneses rezonanciás (MR-) vizsgálat történt. A beteg szteroidkezelésben részesült, melynek hatására az organomegalia csökkenése volt detektálható. Az aktivitási tünetként értékelt fokozódó ichthyosiform bőrfolyamat és perzisztáló lymphadenopathia miatt mikofenolátmofetil-kezelés került bevezetésre, mely hatásosnak bizonyult: mind a klinikai tünetek, mind a laboratóriumi paraméterek alapján tartós remisszió észlelhető. Esettanulmányunk a gyakori klinikai tünetként ismert nyaki lymphadenopathia hátterében álló ritka kórképre hívja fel a figyelmet. A kórkép diagnózisának felállításában a képalkotó vizsgálatok mellett speciális laboratóriumi vizsgálatok, illetve a szövettani lelet segíthet. A betegség kezelésében a szervi manifesztációk mértékének függvényében különböző immunszuppresszív kezelés alkalmazása szükséges. | Enlargement of the cervical lymph nodes is a common phenomenon in childhood. In addition to benign, transient symptoms, severe pathologies may also underlie the symptoms. The authors present the case of an adolescent boy who was admitted to our clinic because of a progressive cervical lymph node enlargement that had been present for several months. Laboratory investigations did not suggest malignancy, and biopsy was performed to clarify the exact etiology. Histopathological examination showed immunoglobulin G4 (IgG4-) related disease. The typical laboratory findings and the characteristic skin lesions (ichthyosis) supported the histopathological findings. Positron emission tomography (18FDG-PET/CT) and abdominal magnetic resonance (MR) scans were performed to rule out other organ manifestations. The patient was treated with steroids, which resulted in a significant reduction in organomegaly. Due to a severe skin flare and persistent lymphadenomegaly assessed as an activity symptom, mycophenolate mofetil treatment was introduced. The treatment proved effective with sustained remission observed in clinical symptoms and laboratory parameters. This case report highlights a rare pathology underlying cervical lymphadenopathy, a common clinical presentation. In addition to imaging studies, special laboratory tests and histopathological findings may help diagnose this pathology. Treating the disease requires using different immunosuppressive regimens depending on the extent of the organ manifestations

Comprehensive profiling of disease-relevant copy number aberrations for advanced clinical diagnostics of pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia is the most common pediatric cancer characterized by a heterogeneous genomic landscape with copy number aberrations occurring at various stages of pathogenesis, disease progression, and treatment resistance. In this study, disease-relevant copy number aberrations were profiled in bone marrow samples of 91 children with B- or T-cell precursor acute lymphoblastic leukemia using digital multiplex ligation-dependent probe amplification (digitalMLPA(TM)). Whole chromosome gains and losses, subchromosomal copy number aberrations, as well as unbalanced alterations conferring intrachromosomal gene fusions were simultaneously identified with results available within 36 hours. Aberrations were observed in 96% of diagnostic patient samples, and increased numbers of copy number aberrations were detected at the time of relapse as compared with diagnosis. Comparative scrutiny of 24 matching diagnostic and relapse samples from 11 patients revealed three different patterns of clonal relationships with (i) one patient displaying identical copy number aberration profiles at diagnosis and relapse, (ii) six patients showing clonal evolution with all lesions detected at diagnosis being present at relapse, and (iii) four patients displaying conserved as well as lost or gained copy number aberrations at the time of relapse, suggestive of the presence of a common ancestral cell compartment giving rise to clinically manifest leukemia at different time points during the disease course. A newly introduced risk classifier combining cytogenetic data with digitalMLPA(TM)-based copy number aberration profiles allowed for the determination of four genetic subgroups of B-cell precursor acute lymphoblastic leukemia with distinct event-free survival rates. DigitalMLPA(TM) provides fast, robust, and highly optimized copy number aberration profiling for the genomic characterization of acute lymphoblastic leukemia samples, facilitates the decipherment of the clonal origin of relapse and provides highly relevant information for clinical prognosis assessment.Cancer Signaling networks and Molecular Therapeutic

Next-Generation Sequencing–Based Genomic Profiling of Children with Acute Myeloid Leukemia

Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML Berlin-Frankfurt-Münster protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients. Considerable differences were observed in the mutational profiles compared with previous studies, as BCORL1, CUX1, KDM6A, PHF6, and STAG2 mutations were detected at a higher frequency than previously reported, whereas KIT, NRAS, and KRAS were less frequently mutated. Our study identified novel recurrent mutations at diagnosis in the BCORL1 gene in 9% of the patients. Tumor suppressor gene (PHF6, TP53, and WT1) mutations were found to be associated with induction failure and shorter event-free survival, suggesting important roles of these alterations in resistance to therapy and disease progression. Comparison of the mutational landscape at diagnosis and relapse revealed an enrichment of mutations in tumor suppressor genes (16.2% versus 44.4%) and transcription factors (35.1% versus 55.6%) at relapse. Our findings shed further light on the heterogeneity of pediatric AML and identify previously unappreciated alterations that may lead to improved molecular characterization and risk stratification of pediatric AML