Predictive Factors for Gram-negative Versus Gram-positive Bloodstream Infections in Children With Cancer.

BACKGROUND: Identifying potential predictive factors for the type of bacteremia (Gram-negative vs. Gram-positive) in children with cancer would be crucial for the timely selection of the appropriate empiric antibiotic treatment. MATERIALS AND METHODS: Demographic, clinical, and laboratory characteristics of children with cancer and a bacterial bloodstream infection (BSI) (February 1, 2011 to February 28, 2018) in a tertiary pediatric oncology department were retrospectively examined and were correlated with the type of isolated bacteria. RESULTS: Among 224 monomicrobial bacterial BSI episodes, Gram-negative and Gram-positive bacteria were isolated in 110 and 114 episodes, respectively. Gram-negative bacteria were isolated significantly more frequently in girls (Gram-negative/Gram-positive ratio 1.7:1) versus boys (Gram-negative/Gram-positive ratio 0.72:1), P=0.002, in patients with previous BSI episodes (1.4:1) versus those without (0.8:1), P=0.042, and in children with hematologic malignancy (1.3:1) versus those who suffered from solid tumors (0.52:1), P=0.003. Gram-negative BSI episodes were more frequently correlated with a lower count of leukocytes, P=0.009, neutrophils, P=0.009 and platelets, P=0.002, but with significantly higher C-reactive protein (CRP) levels, P=0.049. Female sex, hematologic malignancy, and higher CRP levels remained independent risk factors for Gram-negative BSI in the multivariate analysis. Among neutropenic patients, boys with solid tumors and a recent central venous catheter placement appear to be at increased risk for Gram-positive BSI in the multivariate analysis. CONCLUSIONS: Although Gram-negative and Gram-positive BSIs are close to balance in children with cancer, Gram-negative bacteria are more likely to be isolated in girls, children with hematologic malignancies and those with higher CRP level at admission. In contrast, neutropenic boys with solid tumors and a recently placed central venous catheter may be at increased risk for Gram-positive BSI indicating probably the need for initially adding antibiotics targeting Gram-positive bacteria.

Children with progressive and relapsed pleuropulmonary blastoma: A European collaborative analysis.

BACKGROUND: Children with progressive (PD) or relapsed disease (RD) of pleuropulmonary blastoma (PPB) type II/III are known to have a very poor outcome. METHODS: A retrospective review of children registered in national and European databases and trials (2000-2018) with diagnosis of PPB type II/III and PD or RD was performed. RESULTS: A total of 35 patients with PPB were analysed: patients with PD (n = 9) and RD (n = 26). Patients experienced PD at the median age of 3.9 years [range, 0.5-17.8] despite surgery, chemotherapy (CHT, n = 9) and radiotherapy (RT, n = 1) with a median time to progression of 0.58 years [range, 0.02-1.27] from diagnosis. All of them died. Patients suffered from RD at the median age of 4.3 years [1.7-15.1], median delay to relapse 1.03 years [range, 0.03-2.95]. RD occurred locally (n = 12), combined (n = 1) and in metastatic sites (n = 13): central nervous system (n = 11) and unspecified site (n = 2). Patients were treated with salvage CHT (n = 20), surgery (n = 10) ± RT (n = 10). After a median follow-up of 4.2 years [range, 2.1-14.6], a second complete remission (CR) was achieved in nine out of 26 patients. Patients were alive in the second CR (n = 6), in the third CR (n = 1), in partial remission (n = 2) and lost of follow-up (n = 1). Five-year event-free survival (EFS) and overall survival (OS) for patients with RD were both 37% (±19, CI 95%). Local therapy (surgery, RT) had a favourable impact on OS (p = 0.03 and 0.02, respectively). CONCLUSIONS: Cure of patients with RD of PPB type II/III with multimodal treatment is possible but rare. Progressive PPB is fatal and patients need new treatment options.

Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents.

As part of the European Union-funded project designated Paediatric Rare Tumours Network - European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5-flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN-ß) for selected high-risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long-term treatment-related complications that affect most of the survivors.

Clinical utility of miR-143/miR-182 levels in prognosis and risk stratification specificity of BFM-treated childhood acute lymphoblastic leukemia.

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.

Incidence and survival of gliomatosis cerebri: a population-based cancer registration study.

Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern of diffuse gliomas. We explored the incidence patterns and survival rates of GC in a population-based registration sample from the Surveillance, Epidemiology and End, Results database (1973-2012). GC cases (n = 176) were identified based on their International Classification of Diseases in Oncology (ICD-O-3) morphology code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated temporal trends. Survival was assessed with Kaplan-Meier curves and Cox regression models. The annual AIR of GC was 0.1/million. We noted increasing trends in the preceding registration years (1973-2002; annually, + 7%) and a tendency of clinical/radiological approaches to substitute the gold-standard histological assessment for diagnosis. GC was diagnosed in the entire age spectrum (range 1-98 years), but higher incidence rates (0.43/million) were noted among the elderly (≥ 65 years). A slight male preponderance was identified (male-to-female ratio: 1.4). Median overall survival was 9 months with a 5 year survival rate of 18%. Increasing age, primary tumor location not restricted to the cerebral hemispheres and rural residence at diagnosis were identified as negative prognostic factors, whereas receipt of radiotherapy, surgical treatment, race and method of diagnosis were not associated with outcome. This first comprehensive overview of GC epidemiology exemplifies the rarity of the disease, provides evidence for male preponderance and increased incidence among the elderly and shows lower survival rates compared to the published single center reports. Expansion of registration to histological and molecular characteristics would allow emergence of clinical prognostic factors at the population level.

Malignant central nervous system tumors among adolescents and young adults (15-39 years old) in 14 Southern-Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns.

BACKGROUND: Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program. METHODS: Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573). RESULTS: Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions. CONCLUSIONS: Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. Cancer 2017;123:4458-71. © 2017 American Cancer Society.

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.

Optic pathway glioma in children: 10 years of experience in a single institution.

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.

Prayer and blessings focused for healing is the most popular complementary intervention in a paediatric oncology unit in Greece.

PURPOSE: Increasing numbers of children with cancer are using complementary and alternative medicine (CAM) therapies. Our aim was to estimate the rate of use, the beliefs of users and non-users and factors related with the use of CAM among Greek families. METHODS: A self-reported questionnaire was given to parents of 184 children with cancer. We assessed the rate of use, types of CAM therapies and factors potentially associated with the use of CAM. RESULTS: Based on the 110 questionnaires which were completed (59.8% of the families), 23 families (21%) had used at least one complementary treatment. The most common forms were: spiritual healing/prayer/blessings 18/23 (78%), art therapies 4, dietary supplements 3, massage 3, homeopathy 2, and herbals 2. The reasons given for use included: making the child stronger 17/23 (48%, hope of stopping the cancerous process 11/23 (49%), and coping with side effects 6/23 (26%). Among the reasons given by the parents for not using CAM therapies the most common (84%) was the effective conventional treatment and, therefore, there was no need for CAM use. Another 24% reported that were unaware of these "alternative" and "complementary" therapies and a further 7% had considered using them but finally they didn't. In bivariate analysis, the use of CAM was not associated either with age, sex, nationality, education or occupation of the parents at the time of the survey, or with diagnosis, mode of therapy or age of the child at diagnosis. CONCLUSIONS: The use of CAM therapies by Greek families for their children with cancer does not appear to be very popular, although the experiences of those who did use them were generally positive.

A novel karyotype in acute myeloid leukemia with basophilia.

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.

Childhood leukemia and lymphoma: time trends and factors affecting survival in five Southern and Eastern European Cancer Registries.

PURPOSE: Within Europe, incidence and mortality rates of childhood leukemia and lymphoma are rather heterogeneous. The present study comprising data from five Southern and Eastern European Cancer Registries aims to compare time trends and examine whether sociodemographic variables, clinical parameters, and proxies of efficient care affect survival. METHODS: Data spanning 1996-2010 were obtained for a total of 3,041 newly diagnosed childhood leukemia and 1,183 lymphoma cases reported by the Greek Nationwide Registry for Childhood Hematological Malignancies, Bulgarian National Cancer Registry, Moscow Region and Turkey (Antalya and Izmir) Cancer Registries. Poisson modeling for the evaluation of time trends and multivariate Cox regression analysis for the assessment of prognostic factors were performed. RESULTS: The incidence of leukemia was increasing in all cases, with Bulgaria and Greece presenting statistically significant annual changes (+3.5, and +1.7 %, respectively), followed by marginally increasing trends in Izmir and Moscow; by contrast, there was a remarkable, statistically significant, decreasing mortality trend for leukemia. Rates for lymphoma remained flat. Greece experienced almost twofold better survival rates for both leukemia and lymphoma, probably due to its higher socioeconomic status during the study period. Overall, patients with leukemia living in rural areas had a 28 % lower prognosis (RR: 1.28, 95 % CI 1.03-1.59), pointing to effects of remoteness, when the most privileged country (Greece) was excluded from the analysis. CONCLUSIONS: The favorable mortality trends highlight the progress in Southern-Eastern European countries along their trajectory to converge with Northern-Western EU counterpart states. Socioeconomic status may act as a multipotent factor underlying the study findings.

Differences between younger and older patients with childhood hodgkin lymphoma.

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.

Compliance with immunization against H1N1 influenza virus among children with cancer.

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.

In vitro fertilization and risk of childhood leukemia in Greece and Sweden.

BACKGROUND: Cancer risk in children born after in vitro fertilization (IVF) remains largely unknown. We aimed to investigate risk of leukemia and lymphoma following IVF using two nationwide datasets. METHODS: The hospital-based case-control study in Greece derived from the National Registry for Childhood Hematological Malignancies (1996-2008, 814 leukemia and 277 lymphoma incident cases with their 1:1 matched controls). The Swedish case-control study was nested in the Swedish Medical Birth Register (MBR) (1995-2007, 520 leukemia and 71 lymphoma cases with their 5,200 and 710 matched controls) with ascertainment of incident cancer cases in the National Cancer Register. Study-specific and combined odds ratios (OR) were estimated using conditional logistic regression, with adjustment for possible risk factors. RESULTS: Nationwide studies pointed to similar size excess risk of leukemia following IVF, but to a null association between IVF and lymphoma. The proportion of leukemia cases conceived through IVF was 3% in Greece and 2.7% in Sweden; prevalence of IVF in matched controls was 1.8% and 1.6%, respectively. In combined multivariable analyses, the increased risk of leukemia was confined to age below 3.8 years (OR = 2.21; 95% confidence interval, CI: 1.27-3.85) and to acute lymphoblastic leukemia (ALL) (OR = 1.77; 95% CI: 1.06-2.95) with no sufficient evidence of excess risk for other leukemias (OR = 1.34; 95% CI: 0.38-4.69). Following IVF, OR for ALL was 2.58 (95% CI: 1.37-4.84) before age 3.8 and 4.29 (95% CI: 1.49-12.37) before age 2 years. CONCLUSIONS: IVF seems to be associated with increased risk of early onset ALL in the offspring.

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.

Second malignant neoplasms after treatment of non-Hodgkin's lymphoma-a retrospective multinational study of 189 children and adolescents.

Data on the spectrum of second malignant neoplasms (SMNs) after primary childhood non-Hodgkin's lymphoma (NHL) are scarce. One-hundred-and-eighty-nine NHL patients diagnosed in a 30 years period of 1980-2010 developing an SMN were retrieved from 19 members of the European Intergroup for Childhood NHL and/or the international Berlin-Frankfurt-Münster Study Group. Five subgroups of SMNs were identified: (1) myeloid neoplasms (n = 43; 23%), (2) lymphoid neoplasms (n = 51; 27%), (3) carcinomas (n = 48; 25%), (4) central nervous system (CNS) tumors (n = 19; 10%), and (5) "other" SMNs (n = 28; 15%). In 37 patients (20%) preexisting disorders were reported with 90% having any kind of cancer predisposition syndrome (CPS). For the 189 primary NHL patients, 5-year overall survival (OS) after diagnosis of an SMN was 56 ± 4%, being worst for patients with preexisting disorders at 28 ± 8%. Five-year OS rates were 38 ± 8%, 59 ± 7%, 79 ± 8%, 34 ± 12%, and 62 ± 11%, respectively, for patients with myeloid and lymphoid neoplasms, carcinomas, CNS tumors, and "other" SMNs (p < 0.0001). Patients with SMNs after childhood NHL having a reported CPS, mostly mismatch repair disorders, carried a very poor prognosis. Moreover, although outcome was favorable in some subtypes of SMNs after childhood NHL (carcinomas, lymphoid neoplasms), other SMNs such as myeloid neoplasms and CNS tumors had a dismal prognosis.