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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. [ABSTRACT FROM AUTHOR]

Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children. [ABSTRACT FROM PUBLISHER]

Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5-10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32,18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear. [ABSTRACT FROM AUTHOR]

From 1979 to 2006, 74 children with Hodgkin's lymphoma were treated at our center. Among them, 15 (14 boys and 1 girl) and 59 (33 boys and 26 girls) patients were younger and older than 8 years, respectively. Six (40%) children among younger patients and 26 (44%) among older patients had advanced stage disease. We detected 3 (20%) relapses among younger patients and 5 (8.5%) among the older patients. All of younger patients are alive whereas three of the older patients have died. Second malignancy developed in one and three children among younger and older patients, respectively. The only difference that was detected concerning the age was a male predominance among the younger patients. [ABSTRACT FROM AUTHOR]

During the last 30 years, combined chemotherapy regimens with radiotherapy or not significantly improved the prognosis for patients with Hodgkin lymphoma. We retrospectively studied 58 children (35 boys and 23 girls) with Hodgkin lymphoma who were treated at our institution during the period 1987-2006 and we correlated age, sex, stage, histology, and therapy with the outcome of patients. Of our patients, 9 children were 8 years old or younger. Nodular sclerosis was the predominant histology subtype (69%), whereas 26 patients (45%) had advanced disease (stage III or IV). Chemotherapy (CT) with various drug combinations, according to the period of treatment plus low-dose involved field radiation therapy (IFRT), was used in all patients. Five children experienced relapse and in 3 other patients second or third malignancies were documented. The overall survival was found to be 98%. No factors related to the outcome could be detected. The prognosis of children with Hodgkin lymphoma is excellent with CT combined with low dose IFRT but in long-time survivors late effects of the combined modality treatment are still issues of major concern. Longer followup of a greater number of patients is necessary to detect prognostic factors related to the outcome of children with Hodgkin lymphoma and to identify some patients who would be treated without radiation. [ABSTRACT FROM AUTHOR]

Background: Gliomatosis cerebri is a rare but fatal widespread infiltrating central nervous system tumor. We aimed to describe diagnostic and prognostic features of gliomatosis cerebri among children and adolescents. Methods: We conducted a systematic literature review for published case reports and case series on patients with histologically confirmed gliomatosis cerebri and extracted data on an individual patient level for those aged 0-18 years. Multivariable Cox proportional hazard models were fit for overall survival. Results: Following screening of 274 published studies, 182 gliomatosis cerebri patients (63% males) aged 0-18 years with individual-level data available were identified. The most common presenting symptoms were seizures (52%), focal motor deficits (36%), and headache (30%). Imaging showed bilateral hemisphere involvement in 60%, infratentorial infiltration in 39%, and a focal contrast-enhanced mass (type II gliomatosis cerebri) in 27% of cases. Anaplastic astrocytoma was the most common histologic subtype of pediatric gliomatosis cerebri, whereas MGMT promoter methylation, IDH1 mutations, and codeletion of 1p/19q were less common molecular aberrations, as compared to adult gliomatosis cerebri. In the multivariable analyses, age at diagnosis >4 years, extended central nervous system infiltration, coordination abnormalities, and cognitive decline were predictors of worse outcome. Conversely, IDH1 mutations were associated with prolonged overall survival. Chemotherapy and extended surgical resection were associated with improved outcome, whereas radiotherapy was not associated with overall survival and was inferior to chemotherapy alone. Conclusion: Gliomatosis cerebri among children and adolescents presents distinct histopathologic and molecular features compared to adults. However, similar associations of chemotherapy, and, when feasible, extended surgical resection, with favorable outcomes were noted among the 2 age groups. [ABSTRACT FROM AUTHOR]

A13-year-old girl was admitted to our departmentwith a history of severe pain of her left axilla and fever. Onphysical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian regionwere noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL), whereasDNAofMycobacteriumtuberculosis was detected by polymerase chain reaction (PCR) in the same tissue biopsy. Patientwas started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two newnodular lesionswere detected in the left lower lobe. Biopsy revealed granulomas, and PCRwas positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months), pyrazinamide (the first 2 months), and maintenance chemotherapy for herALCL for one year simultaneously. Four years later, she is disease free for bothmycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time. [ABSTRACT FROM AUTHOR]

The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease in remission, who developed autoimmune anemia and thrombopenia. He was treated with high-dose steroids and he developed serious invasive lung aspergillosis, which was treated with antifungal agents and surgical intervention. Children suffering from cancer are prone to develop systemic fungal infections secondary to the severe immunosuppression caused by the disease itself and the antineoplastic therapy. Intravenous antifungal medications and, when feasible, surgery are used for treatment of pulmonary aspergillosis. Factors related to better outcome are early diagnosis, remission of underlying disease, aggressive antifungal therapy, and recovery from neutropenia. [ABSTRACT FROM AUTHOR]

Candidemia is an important cause of morbidity and mortality especially in immunocompromised and hospitalized patients. We retrospectively collected data of candidemia cases that occurred in the seven Hematology-Oncology Departments/Units of Greece and the Stem Cell Transplant Unit between 2015 and 2019. In total, 19 episodes of candidemia in 19 patients were recorded. The majority of the patients (78.9%) had at least one risk factor for candidemia. The most frequent risk factors associated with candidemia observed in our patients were prolonged duration of hospitalization (30 days, range 1-141), presence of a central venous catheter at diagnosis of candidemia (73.7%) and antibiotics use during the last two weeks (84.2%). Candida parapsilosis was the most common species isolated accounting for 42.1%, followed by C. albicans (26.3%) and C. famata (15.8%). Nearly all of the patients (84.2%) received antifungal monotherapy with liposomal amphotericin B or echinocandins. The central venous catheter was removed in 78.6% of patients and the median time between the first positive blood culture and catheter removal was 3 days (range 1-9). Mortality at 28 days was 26.3%. In conclusion, a predominance of non-albicans species was observed in our study in conformity with the global trend. [ABSTRACT FROM AUTHOR]

Although childhood acute lymphoblastic leukemia (ALL) is characterized by high remission rates, there are still patients who experience poor response to therapy or toxic effects due to intensive treatment. In the present study, we examined the expression profile of miR-143 and miR-182 in childhood ALL and evaluated their clinical significance for patients receiving Berlin-Frankfurt-Münster (BFM) protocol. Bone marrow specimens from 125 childhood ALL patients upon diagnosis and the end-of-induction (EoI; day 33), as well as from 64 healthy control children undergone RNA extraction, polyadenylation, and reverse transcription. Expression levels of miRNAs were quantified by qPCR analysis. Patients' cytogenetic, immunohistotype and MRD evaluation was performed according to international guidelines. Median follow-up time was 86.0 months (95% CI 74.0-98.0), while patients' mean DFS and OS intervals were 112.0 months (95% CI 104.2-119.8) and 109.2 months (95% CI 101.2-117.3), respectively. Bone marrow levels of miR-143/miR-182 were significantly decreased in childhood ALL patients at diagnosis and increased in more than 90% of patients at the EoI. Patients' survival analysis highlighted that children overexpressing miR-143/miR-182 at the EoI presented significantly higher risk for short-term relapse (log-rank test: p = 0.021; Cox regression: HR = 4.911, p = 0.038) and death (log-rank test: p = 0.028; Cox regression: HR = 4.590, p = 0.046). Finally, the evaluation of the miR-143/miR-182 EoI levels along with the established disease prognostic markers resulted to improved prediction of BFM-treated patients' survival outcome and response to therapy and additionally to superior BFM risk stratification specificity. Concluding, miR-143 and miR-182 could serve as novel prognostic molecular markers for pediatric ALL treated with BFM chemotherapy. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila is a Gram negative organism causing both intestinal and extraintestinal disease. The case of a 14-year-old girl with underlying immunodeficiency and leukemia who developed systemic A. hydrophila infection is described in this report. While in deep bone marrow aplasia she developed fever, severe pain in the lower extremities, and swelling of the left femur. Blood culture showed Escherichia coli and A. hydrophila whereas pus culture from the soft tissue swelling showed the presence of A. hydrophila. Imaging studies showed diffuse osteolytic lesions. Patient received 5 months of intravenous and oral antibiotics and she improved clinically whereas the radiology findings persisted. [ABSTRACT FROM AUTHOR]

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, −21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity. [ABSTRACT FROM AUTHOR]

In this report, we describe the experience with immunization against pandemic influenza A H1N1 in children with cancer treated at a pediatric oncology department during the pandemic season (2009). According to the guidelines, vaccination of all children with cancer receiving chemotherapy as well as those who had completed treatment was scheduled. Among the 140 children who were eligible for immunization, 122 were immunized, achieving a compliance rate of 87% despite negative publicity and low vaccine uptake in the general population. The vaccine was tolerated and none of the vaccinated children developed influenza. It is concluded that high immunization rates can be achieved among pediatric oncology patients. [ABSTRACT FROM AUTHOR]

Abstract: An increase of the prevalence of childhood allergic diseases and the incidence of childhood Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL) were reported in the late 20th century. Among adults, several studies point to an inverse association with lymphoma; it remains to be confirmed whether allergy is also related to childhood lymphomas and whether the association, if any, is of an aetiologic nature. Between 1996 and 2008, 277 children (aged 0–14years) with HL (N =111) or NHL (N =166) were enrolled in Nationwide Registry for Childhood Hematological Malignancies (NARECHEM), a Greek hospital-based-registry of childhood hematological malignancies. Hospital controls were individually matched to cases on age and sex. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95%confidence intervals (CIs) for associations of allergic diseases and other covariates with childhood HL or NHL risk. Subsequently, we combined our results with those of a French case–control study in a meta-analysis amounting to a total of 330 NHL cases/1478 controls and 239 HL cases/959 controls. After controlling for sociodemographic, perinatal and environmental factors, childhood NHL was less prevalent among children with allergy-associated symptoms overall (OR:0.50, 95%CI:0.27–0.92) or a history of asthma (OR:0.43, 95%CI:0.21–0.88). By contrast, allergy did not seem to be associated with childhood HL risk, although statistical power was limited. Fewer seaside holidays and higher birth weight were also associated with increased childhood NHL risk. The combined OR of the two studies for the association of asthma with NHL risk was: 0.52, 95%CI:0.32–0.84, whereas for HL: 0.86, 95%CI:0.51–1.45. Allergy seems to be strongly and inversely associated with childhood NHL. It remains to be elucidated in future investigations comprising larger populations, focusing on specific disease subtypes and employing more pertinent study-designs, whether this association is genuinely protective. [ABSTRACT FROM AUTHOR]

Abstract: An increase of the prevalence of childhood allergic diseases and the incidence of childhood Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL) were reported in the late 20th century. Among adults, several studies point to an inverse association with lymphoma; it remains to be confirmed whether allergy is also related to childhood lymphomas and whether the association, if any, is of an aetiologic nature. Between 1996 and 2008, 277 children (aged 0–14years) with HL (N =111) or NHL (N =166) were enrolled in Nationwide Registry for Childhood Hematological Malignancies (NARECHEM), a Greek hospital-based-registry of childhood hematological malignancies. Hospital controls were individually matched to cases on age and sex. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) with 95%confidence intervals (CIs) for associations of allergic diseases and other covariates with childhood HL or NHL risk. Subsequently, we combined our results with those of a French case–control study in a meta-analysis amounting to a total of 330 NHL cases/1478 controls and 239 HL cases/959 controls. After controlling for sociodemographic, perinatal and environmental factors, childhood NHL was less prevalent among children with allergy-associated symptoms overall (OR:0.50, 95%CI:0.27–0.92) or a history of asthma (OR:0.43, 95%CI:0.21–0.88). By contrast, allergy did not seem to be associated with childhood HL risk, although statistical power was limited. Fewer seaside holidays and higher birth weight were also associated with increased childhood NHL risk. The combined OR of the two studies for the association of asthma with NHL risk was: 0.52, 95%CI:0.32–0.84, whereas for HL: 0.86, 95%CI:0.51–1.45. Allergy seems to be strongly and inversely associated with childhood NHL. It remains to be elucidated in future investigations comprising larger populations, focusing on specific disease subtypes and employing more pertinent study-designs, whether this association is genuinely protective. [Copyright &y& Elsevier]

To investigate whether single nucleotide polymorphisms (SNPs) in key cytokine and innate immunity genes influence risk for childhood lymphomas, we genotyped 37 children with Hodgkin’s (HL) and 48 with non-Hodgkin’s lymphoma (NHL), aged (1 month–14 yr), along with their 85 age- and gender-matched controls suffering from mild medical conditions. Genotypic analysis was performed for 10 SNPs from nine genes with important role in immunoregulatory pathways ( IL4, IL4R, IL6, IL10, IL12, IL18, TNFα, IFNγ, CD14). Analysis of SNPs genotypes revealed that the CD14 −159 C>T polymorphism was associated with significantly increased risk for HL regarding both the CC and CT genotypes (ORCC: 5.36; 95% CI, 1.30–22.14; P = 0.02, ORCT: 3.76; 95% CI, 1.00–14.16; P = 0.05). An indicative association between IL18−137 G>C polymorphism with the CC genotype and NHL did not reach, however, statistical significance (ORCC, 3.78; 95% CI, 0.87–16.38; P = 0.08). In conclusion, our findings suggest that genetic variation in the CD14–159 loci may be associated with childhood HL risk; these preliminary findings need to be further confirmed in sizeable multi-centre studies along with determination of cytokines, which could provide an insight on the biologic basis underlying these findings. [ABSTRACT FROM AUTHOR]

Neurofibromatosis-1 (NF-1) is a multisystem disorder presenting with a variety of clinical and imaging manifestations. Neural and non-neural tumours, and unusual benign miscellaneous conditions, separately or combined, are encountered in variable locations. We present a 2(1/2)-year-old boy with NF-1 who demonstrated coexisting optic pathway glioma with involvement of the chiasm and optic nerve, orbital alveolar rhabdomyosarcoma and bilateral optic nerve sheath dural ectasia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to examine the effects of a known neurotoxic regimen, such as the acute lymphocytic leukemia (ALL) Berlin-Frankfurt-Münster 95 (ALL-BFM-95) protocol, on the function of the medial olivocochlear bundle, which was assessed by recording suppression of the amplitudes of distortion-product otoacoustic emissions (DPOAEs) when white noise was applied simultaneously to the contralateral ear. METHODS: Our population consisted of 3 groups of children with ALL. A baseline examination was performed before the beginning of therapy. DPOAE-suppression measurements were repeated after 4 weekly doses of vincristine in the first group (n = 12), after 8 weekly doses in the second group (n = 12), and 3 years after completion of the protocol in the third group (n = 23). In the third group, a subgroup of 12 children who were exposed to low-dose gentamicin (<13 days) and another 11 children who were exposed to high gentamicin doses (>23 days) were evaluated. RESULTS: At baseline examination, all groups presented significant suppression at all frequencies. Efferent mediated DPOAE suppression was still present after 4 sessions of vincristine. However, after 8 vincristine sessions, instead of suppression, an increase of amplitudes was noted at 5 (of 12) frequencies. In the subgroups examined 3 years after ALL-BFM-95, the olivocochlear reflex had recovered. CONCLUSIONS: Enhancement or no significant suppression of OAEs by contralateral noise indicates a probable vincristine-induced insult to the efferent cochlear innervation. This adverse effect seems to take place early in the course of chemotherapy and is slowly reversed a few years after chemotherapy. The clinical implications of these findings may need additional investigation. [ABSTRACT FROM AUTHOR]