Objective: To document characteristics and outcome in children with Langerhans cell histiocytosis (LCH) in Greece. Methods: A retrospective review of patients with biopsy-proven LCH treated in pediatric-hematology-oncology units was undertaken. Results: Between 2000-2019, LCH was diagnosed in 169 patients (62.7% males) with median age 4.76 years (37.8% <2 years old). One-hundred-thirty-three (78.7%) had single-system (SS) disease; bone 110/133 (82.7%), 4 with diabetes insipidus (DI): 67 (50.4%) were only observed and 5 (7.5%) relapsed. With median follow-up-time (MFupT) 4.2 years (range, 0.1-19.7), all are alive in complete remission (CR), with overall survival (OS) 100% and event-free survival (EFS) 92.5%. Seventy-one (53.4%) patients with SS-disease received systemic chemotherapy (66/71 as initial treatment). At MFUpT time of 6.51 years (range, 0.1-19.7), OS and EFS were 98.4% and 85.7%, with 2 deaths (pneumothorax, lymphoma). Multi-system (MS) disease (2-5 systems) had 36 patients (21.3%), median-age 1.7 years (range, 0.04-10.35 / 58.3% <2 years), 28/36 (77,8%) had bone involvement and 44,4% (16/36) Risk-Organ involvement, while 10/36 (27.8%) presented with DI. Most MS-patients (91.7%) received Prednisolone/Vinblastine for a median duration of 12 months (range, 1-43); OS and EFS were 97.2% and, 75.0%, with MFUpT 6.39 years (range, 0.5-20.2). Twenty-seven patients out of 51 tested, were found BRAF-V600E+ (52.9%); the probability of relapse was significantly higher in BRAF-600E mutated patients (p=0,014). Discussion: Disease and outcome data of the Greek LCH National Registry cohort are comparable with international data, with favorable results. This work formed the basis for LCH-IV Protocol national participation, supported by Histiocytosis Hellas.

Background: Fanconi anemia (FA) is a rare genomic instability disorder, characterized by congenital abnormalities, progressive bone marrow failure and predisposition to cancer. FA is caused by (likely) pathogenic variants in any of the 23 ( FANCA-FANCY) linked genes. Procedure: Retrospective analysis of 13 FA patients with a causative variant was performed to allow insights into FA. Patients (6 boys and 7 girls) aged from 9 to 26 years old, (mean age of 7.3 years), at diagnosis. Results: Phenotype evaluation demonstrated in 11/13 patients’ congenital anomalies, primarily pigmentary changes and short stature, in 90% of cases. Haematological abnormalities were present in 10/11 patients, with thrombocytopenia being the prominent finding. Genetic analysis for the most common complementation group FA-A revealed that 12/13 patients belonged to this group and only one patient was found to be FA-E. Exon deletions, single nucleotide variations, and duplications were identified. Familial patterns, due to consanguinity, were evident in one case. Twelve patients underwent hematopoietic stem cell transplantation (HSCT), with variable pre-HSCT supportive treatments. Post-HSCT data showed that 9 out of 10 patients for whom follow up data was available, survived for a median time of 5.4. Complications like acute graft-versus-host disease were noted. Conclusions: Our study highlights the importance of genotype-phenotype correlations towards tailored clinical management including the optimum time for HSCT in patients with FA.

Survival of high risk neuroblastoma patients is increased with the use of dinutuximab beta (DB). This anti-ganglioside 2 antibody promotes neuroblastoma cell killing but has on-target off-tumor nervous system side effects. A patient with high-risk neuroblastoma treated with DB and cis-retinoic acid without interleukin-2 presented with severe encephalopathy. Prompt commencement of acyclovir, steroids and intravenous immunoglobulin infusions proved unsuccessful. Symptomatic improvement concurred with the initiation of high-dose steroid pulses and serial plasmapheresis sessions. Timely management of severe DB neurotoxicity as immune-based encephalomyelitis and prompt initiation of plasmapheresis, if needed, can reverse symptoms and offer long-term recovery of the patients.