Hodgkin Lymphoma in Children and Adolescents of Northern Greece: 25-Year Results and Long-term Follow-up.

Aim of this study was to evaluate the long-term therapeutic outcome and treatment-related complications in Hodgkin disease. We reviewed the medical records of 93 patients diagnosed with classic Hodgkin lymphoma, treated, and followed-up during the last 25 years. The cohort study included 49 males and 44 females with median age 11.8 years old (range: 3.95 to 17.42 y). The most common subtype was nodular sclerosis in 47/93 (50.5%). B symptoms were present in 15/93 (16.1%). From January 2009 until December 2020, 55 (59%) patients diagnosed with Hodgkin lymphoma were treated according to European Network for Pediatric Hodgkin Lymphoma (EURONET)-PHL-C1 protocol. Concerning outcome, a total of 89/93 patients are alive. Relapse occurred in 7/93. Second malignancies are reported in a total of 5 patients, 3 solid tumors (thyroid cancer, breast cancer, and osteosarcoma), and 2 acute myeloid leukemias. The overall survival and event-free survival for the whole cohort were 95.7% and 83.9%, respectively. Disease-free survival was 92.5%. Although a considerable high fraction of patients with Hodgkin disease can achieve continuous complete remission, they are at a high risk of developing long-term treatment-related complications. High curative rates as well as prevention of late effects can be achieved by implementation of individualized treatment strategies and innovative treatments.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

Childhood (0-14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern-Eastern European (SEE) countries and those in the United States. Average age-standardized mortality rates and time trends of Hodgkin (HL) and non-Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990-2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990-2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan-Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/106 ), which presented a sizeable (-4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non-HL was associated with a poorer outcome and an amphi-directional age-specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28-1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46-0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype-specific, and age-specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs.

Incidence, time trends and survival patterns of childhood pilocytic astrocytomas in Southern-Eastern Europe and SEER, US.

Pilocytic astrocytomas (PA) comprise the most common childhood central nervous system (CNS) tumor. Exploiting registry-based data from Southern and Eastern Europe (SEE) and SEER, US, we opted to examine incidence, time trends, survival and tentative outcome disparities of childhood PA by sociodemographic and clinical features. Childhood PA were retrieved from 12 SEE registries (N = 552; 1983-2014) and SEER (N = 2723; 1973-2012). Age-standardized incidence rates (ASR) were estimated and survival was examined via Kaplan-Meier and Cox regression analysis. ASR of childhood PA during 1990-2012 in SEE was 4.2/106, doubling in the USA (8.2/106). Increasing trends, more prominent during earlier registration years, were recorded in both areas (SEE: +4.1 %, USA: +4.6 %, annually). Cerebellum comprised the most common location, apart from infants in whom supratentorial locations prevailed. Age at diagnosis was 1 year earlier in SEE, whereas 10-year survival was 87 % in SEE and 96 % in SEER, improving over time. Significant outcome predictors were age <1 year at diagnosis diagnosis (hazard ratio, HR [95% confidence intervals]: 3.96, [2.28-6.90]), female gender (HR: 1.38, [1.01-1.88]), residence in SEE (HR: 4.07, [2.95-5.61]) and rural areas (HR: 2.23, [1.53-3.27]), whereas non-cerebellar locations were associated with a 9- to 12-fold increase in risk of death. The first comprehensive overview of childhood PA epidemiology showed survival gains but also outcome discrepancies by geographical region and urbanization pointing to healthcare inequalities. The worse prognosis of infants and, possibly, females merits further consideration, as it might point to treatment adjustment needs, whereas expansion of systematic registration will allow interpretation of incidence variations.

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance, Epidemiology and End Results, USA.

PURPOSE: To describe epidemiologic patterns of childhood (0-14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies. METHODS: Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990-2014; incidence rates were estimated and time trends were evaluated. RESULTS: Overall age-adjusted incidence rate was higher in SEE (16.9/106) compared to SEER (13.6/106), because of a higher incidence of Hodgkin (HL, 7.5/106 vs. 5.1/106) and Burkitt lymphoma (BL, 3.1 vs. 2.3/106), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/106 vs. 5.8/106), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE. CONCLUSIONS: Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium.

PURPOSE: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. RESULTS: Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. CONCLUSIONS: Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

Bilateral Eyelid Ptosis, Attributed to Vincristine, Treated Successfully with Pyridoxine and Thiamine in a Child with Acute Lymphoblastic Leukemia.

Vincristine-induced neurotoxicity is an adverse effect commonly seen in pediatric patients treated for cancer. We hereby present a case of a 6-year-old boy with acute lymphoblastic leukemia, who developed bilateral eyelid ptosis 25 days after the last intravenous administration of vincristine (cumulative dose 14.2 mg i.e., 17.75 mg/m(2)). The boy was treated with 5 mg/kg thiamine and with 10 mg/kg pyridoxine. Complete recovery of ptosis was noticed 4 weeks after the initiation of Vitamins B1 and B6 supplementation therapy.

Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia.

BACKGROUND: We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy-induced bacterial infections in children with B acute lymphoblastic leukemia (B-ALL). PROCEDURE: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were determined in children with B-ALL. FCN2 haplotype was determined by gene sequencing. Number and duration of FN episodes as well as number of bacterial infections were recorded during induction chemotherapy. RESULTS: Forty-four children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in 44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not associated with increased frequency of FN episodes. MBL2 medium/high-risk genotype and FCN2 medium/high-risk haplotype were associated with prolonged duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of bacterial infections (P = 0.001 and P = 0.002, respectively). The combined MBL2/FCN2 medium/high-risk genotype was associated with an increased number of bacterial infections (P = 0.001). CONCLUSIONS: MBL2 and FCN2 single or combined deficiencies are associated with increased duration of FN episodes as well as increased number of bacterial infections in children with B-ALL suggesting a prognostic role of these genes.

Combined chelation therapy with deferoxamine and deferiprone in ß-thalassemia major: compliance and opinions of young thalassemic patients.

Treatment of ß-thalassemia major (ß-TM) includes regular blood transfusions and iron chelation with subcutaneous injection of deferoxamine (DFO). During the last decade, a new chelation agent, deferiprone (L1), was introduced. The purpose of our study was to determine the level of awareness/education regarding chelation therapy, the degree of compliance to this therapy and their views of L1 in patients with ß-TM. A relevant questionnaire was administered to 36 patients (12-26 years old) who were on combination chelation therapy with both DFO and L1. The majority of patients was well aware/educated about chelation therapy (76.6%), was compliant with this therapy (74.4%) and had a positive view towards oral chelation (86.0%). In conclusion, most patients with ß-TM who were on combination chelation therapy with DFO and L1 were satisfied with this treatment and this results in high compliance rates.

Effect of apolipoprotein E (APOE) gene polymorphisms on the lipid profile of children being treated for acute lymphoblastic leukemia.

BACKGROUND: Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes. PROCEDURE: We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls. RESULTS: The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence). CONCLUSIONS: Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.

Metabolic Fingerprint in Childhood Acute Lymphoblastic Leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of the disease. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL have a distinct metabolomic fingerprint at diagnosis when compared: (i) to a control group; (ii) to children with a different (sub)type of ALL; (iii) to the end of the induction treatment. MATERIALS AND METHODS: In this prospective case-control study (NCT03035344), plasma and urinary metabolites were analyzed in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analyses were performed using SIMCAP and scripts under the R programming language. RESULTS: Metabolomic analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the patient group differed significantly between common B-ALL and pre-B ALL and between D0 and D33, reflecting the effect of treatment. We have further identified the major components of this metabolic dysregulation, indicating shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipid metabolism, and in the glutaminolysis/TCA cycle. CONCLUSIONS: The disease type and time point-specific metabolic alterations observed in pediatric ALL are of particular interest as they may offer potential for the discovery of new prognostic biomarkers and therapeutic targets.

Prognostic factors in high-grade pediatric osteosarcoma among children and young adults: Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data along with a systematic review and meta-analysis.

The 5-year overall survival of children and adolescents with osteosarcoma has been in plateau during the last 30 years. The present systematic review (1976-2023) and meta-analysis aimed to explore factors implicated in the prognosis of children and young adults with high-grade osteosarcoma. Original studies including patients ≤30 years and the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) data (2010-2021) referred to children ≤14 years were analysed. Individual participant data (IPD) and summary estimates were used to assess the n-year survival rates, as well as the association of risk factors with overall survival (OS) and event-free survival (EFS). IPD and the n-year survival rates were pooled using Kaplan-Meier and Cox regression models, and random effects models, respectively. Data from 8412 patients, including 46 publications, NARECHEM-ST data, and 277 IPD from 10 studies were analysed. The summary 5-year OS rate was 64% [95% confidence interval (95%CI): 62%-66%, 37 studies, 6661 patients] and the EFS was 52% (95%CI: 49%-56%, 30 studies, 5010 patients). The survival rates generally differed in the pre-specified subgroups. Limb-salvage surgery showed a higher 5-year OS rate (69%) versus amputation (47%). Good responders had higher OS rates at 3 years (94%) and 5 years (81%), compared to poor responders at 3 years (66%), and 5 years (56%). Patients with metastatic disease had a higher risk of death [Hazard Ratio (HR): 3.60, 95%CI: 2.52, 5.15, 11 studies]. Sex did not have an impact on EFS (HR females/males: 0.90, 95%CI: 0.54, 1.48, 3 studies), whereas age>18 years seems to adversely affect EFS (HR 18+/<10 years: 1.36, 95%CI: 1.09, 1.86, 3 studies). Our results summarize the collective experience on prognostic factors of high-grade osteosarcoma among children and young adults. Poor response to neoadjuvant chemotherapy and metastatic disease at diagnosis were confirmed as primary risk factors of poor outcome. International collaboration of osteosarcoma study groups is essential to improve survival.

Clinical Characteristics and Risk Factors for Bloodstream Infections in Children with Cancer: A Report from a Pediatric Hematology Oncology Unit.

BACKGROUND/AIM: Infections are a major cause of morbidity and mortality in children with haematologic malignancies and solid tumors as well as those undergoing hematopoietic stem cell transplantation (HSCT). The purpose of our study was to record the epidemiological characteristics and outcomes of bacteremias, focusing on pathogens, as well as risk factors and mortality rates in patients of a pediatric hematology-oncology unit from Northern Greece. MATERIALS AND METHODS: A retrospective analysis was conducted, which included all positive blood cultures from pediatric hematology oncology patients aged from 1 to 16 years old admitted to the Pediatric and Adolescent Hematology Oncology Unit of AHEPA University Hospital of Thessaloniki between January 2014 and December 2018. Data were collected from patients' printed and electronic medical records. RESULTS: 73 episodes of bacteremias were identified (41% male and 32% female with a ratio of 1.28:1; median age 6.5 years; 13.7% solid tumor, 72.6% acute lymphoblastic leukemia, 13.7% acute myeloid leukemia, and 95.8% with an indwelling permanent catheter). 49.3% of the isolates were Gram-positive bacteria and 50.7% Gram-negative, and the ratio of Gram-negative to Grampositive was 1.02. Coagulase-negative staphylococci were most frequent (39.7%), followed by E. coli (17.8%) and Klebsiella pneumoniae (17.8%). Out of all Gram-negatives, 13.5% carbapenemase producers and 8.1% ESBL-producers were found. In relation to Gram-positive, 79.3% were identified as methicillin-resistant CoNS. During the study period, 10.9% of indwelling catheters were removed, and 2.73% of episodes resulted in ICU transfer. The 3-month mortality rate was 8.2%. CONCLUSION: This study demonstrated an almost equal distribution of Gram-positive and Gramnegative bacteremias in total in this population but with an increase in the isolation of Grampositive bacteria over the last years, which is consistent with other similar studies in this patient group. Knowledge of the local epidemiology and bacterial antimicrobial resistance is important to prevent and timely treat these life-threatening infections in immunocompromised pediatric oncology patients.

Kinetics and Role of Pancreatic Stone Protein and Midregional Proadrenomedullin as Predictors of Sepsis and Bacteremia in Children with Hematological Malignancies.

Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with hematological malignancies. Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. CRP, PSP, and MR-proADM levels were measured at the onset of the febrile episode (day 1), day 3, and day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as an area under a receiver operating characteristic (ROC) curve. ROC curves were used for each biomarker to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis. Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with hematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%), a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers on day 1 differed significantly between patients with and without sepsis. PSP, MR-proADM, and CRP specificity were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM, and CRP were 0.84, 0.74, and 0.88, respectively. Conclusions: PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with hematological malignancies. However, PSP has a higher sensitivity and specificity.

Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology.

First detection of mcr-1-producing Escherichia coli in Greece.

OBJECTIVES: In this communication, we describe the emergence of the mcr-1 colistin resistance gene in a blaCTX-M-32 extended-spectrum-ß-lactamase-producing Escherichia coli isolate recovered from a pediatric patient in Greece. METHODS: Bacterial identification and antimicrobial susceptibility testing were performed with the VITEK2 automated system and broth microdilution. Detection of resistance genes, assignment to sequence type, in silico plasmid detection, and virulence factors were carried out using ResFinder, MLST 2.0, PlasmidFinder 2.1., and VirulenceFinder 2.0, respectively. PlasmidSPAdes v3.11.1 was used to assemble the plasmid contigs. The mcr-1.1-containing plasmid was analyzed for insertion sequence elements using ISfinder. Phylogenetically relevant sequences of the plasmid were identified using the Microbe BLASTN suite. RESULTS: The microorganism was assigned to sequence type 48 and carried four plasmids of different incompatibility groups. The specific mcr-1.1 allele was located in a 32.722 bp plasmid belonging to the IncX4 group with no additional resistance genes. CONCLUSION: To the best of our knowledge, this is the first detection of mcr-1 in a human specimen in our country. A potential spread of mcr-1 in Greece is concerning because of the existing high rates of carbapenem resistance and colistin usage as a last resort regimen.

Aplastic anemia and paroxysmal nocturnal hemoglobinuria in children and adults in two centers of Northern Greece.

Bone marrow failure (BMF) syndromes are a group of various hematological diseases with cytopenia as a main common characteristic. Given their rarity and continuous progress in the field, we aim to provide data considering the efficiency and safety of the therapeutic methods, focusing on the treatment of aplastic anemia(AA) and paroxysmal nocturnal hemoglobinuria (PNH). We enrolled consecutive patients diagnosed with BMF in two referral centers of Northern Greece from 2008 to 2020. We studied 43 patients with AA (37 adults and 6 children/adolescents) and 6 with classical PNH. Regarding classical PNH, 4 patients have received eculizumab treatment with 1/4 presenting extravascular hemolysis. Among 43 patients with aplastic anemia, PNH clones were detected in 11. Regarding patients that did not receive alloHCT (n=15), 14/15 were treated with ATG and cyclosporine as first line, with the addition of eltrombopag in patients treated after its approval (n=9). With a median follow-up of 16.7 (1.8-56.2) months from diagnosis, 12/14 (85.7%) are alive (4-year OS: 85.1%). AlloHCT was performed in 28 patients. Five patients developed TA-TMA which did not resolve in 3/5 (all with a pre-transplant PNH clone). With the follow-up among survivors reaching 86.3 (6.3-262.4) months, 10-year OS was 56.9%, independently associated with PNH clones after adjusting for age (p=0.024). In conclusion, our real-world experience confirms that novel treatments are changing the field of BMF syndromes. Nevertheless, there is still an unmet need to personalize algorithms in this field.

Safety and Efficacy of Eltrombopag in Children and Adults with Immune Thrombocytopenia: A Systematic Review and Meta-Analysis.

Immune thrombocytopenia is an immune condition where antibodies are produced against platelets. Eltrombopag is a thrombopoietin receptor agonist that stimulates and promotes platelet production approved for treating thrombocytopenia in patients with chronic immune thrombocytopenia, where other treatments such as corticosteroids, splenectomy or immunoglobulins are inadequate. The aim of this meta-analysis was to evaluate the efficacy and safety of the eltrombopag in adults and children with immune thrombocytopenia. We included 7 studies with a total of 765 patients (606 adults and 159 children). We evaluated the number of patients that achieved a post-treatment platelet count equal or above 50x109/L (primary result-target) without the need of rescue treatment for at least 4 weeks. Our data showed that patients who received eltrombopag were almost 4 times more probable in achieving the primary target when compared to patients who received placebo (RR 3.84, 95% CI 2.39 to 6.14; I2 = 46%). The number of patients needed rescue treatment and the number of bleeding incidents were reduced in the group that received eltrombopag when compared to those who received placebo (RR 0.40, 95% CI 0.25 to 0.62; I2 = 40%) (RR 0.74, 95% CI 0.62 to 0.89; I2 = 68%). The total number of side effects did not statistically differ between the two groups (RR 0.99, 95% CI 0.90 to 1.08; I2 = 14%). Our findings were similar to previously published studies and confirm that eltrombopag is safe and efficient in immune thrombocytopenia. However, more clinical trials are needed in order to enhance our findings.

Overall and event-free survival of childhood lymphoma in Greece: analysis of harmonized clinical data over a 24-year active registration period.

We assessed event-free (EFS) and overall (OS) survival in 676 incident cases of childhood Hodgkin (HL) and non-Hodgkin (NHL) lymphoma actively registered in Greece (1996-2019). HL-OS5-year was 96% and NHL-OS5-year 85%, whereas HL-EFS5-year was 86% and NHL-EFS5-year was 81%, notably similar to the respective OS rates (HL: 95%, NHL: 85%) in developed countries. For HL, older age at diagnosis, high maternal education and close proximity to treatment centers were linked to remarkably favorable outcomes. By contrast, stage IV patients showed worse OS and EFS. HL patients with low levels of hemoglobin were associated with worse EFS (hazard ratio: 2.81, 95% confidence intervals: 1.09-7.22). OS (76%) and EFS (73%) were poor among high-risk NHL patients and those with increased LDH (71%). The identified predictors of poor disease outcome point to the need for intensification of individualized treatments. Ongoing clinical cancer registration entailing clinical components could contribute to use of state-of-the-art treatments.