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Over the past two decades, the prognosis in adolescents and young adults (AYAs) diagnosed with acute myeloid leukemia (AML) has significantly improved. The standard intensive cytotoxic treatment approach for AYAs with AML, consisting of induction chemotherapy with anthracycline/cytarabine combination followed by consolidation chemotherapy or stem cell transplantation, has lately been shifting toward novel targeted therapies, mostly in the fields of clinical trials. One of the most recent advances in treating AML is the combination of the B-cell lymphoma 2 (Bcl-2) inhibitor venetoclax with hypomethylating agents, which has been studied in elderly populations and was approved by the Food and Drug Administration (FDA) for patients over 75 years of age or patients excluded from intensive chemotherapy induction schemas due to comorbidities. Regarding the AYA population, venetoclax combination therapy could be a therapeutic option for patients with refractory/relapsed (R/R) AML, although data from real-world studies are currently limited. Venetoclax is frequently used by AYAs diagnosed with advanced hematologic malignancies, mainly acute lymphoblastic leukemia and myelodysplastic syndromes, as a salvage therapeutic option with considerable efficacy and safety. Herein, we aim to summarize the evidence obtained from clinical trials and observational studies on venetoclax use in AYAs with AML. Based on the available evidence, venetoclax is a safe and effective therapeutic option for R/R AML AYA patients. However, further research in larger cohorts is needed to confirm these data, establishing the benefits of a venetoclax-based regimen for this special population.

Adults with β- thalassemia major (β-TM) develop low BMD and fragility fractures at a higher incidence and at a younger age compared to the general population. The disease itself, including direct effects of anemia and iron overload toxicity on bone turnover, genetic susceptibility, thalassemia-related endocrinopathies and acquittance of suboptimal peak bone mass contribute to low bone mass and increased bone fragility frequently encountered among these patients. Current management of osteoporosis requires long-term treatment that can be provided by agents that reduce the risk of all osteoporotic fractures by modulating bone metabolism with different mechanisms of action. These include inhibitors of bone remodeling (e.g., bisphosphonates, denosumab) and stimulators of bone formation (e.g., PTHR1 agonists and sclerostin antibodies). Considering the unique characteristics of osteoporosis associated with β-TM and the clinical importance of balancing the risk/benefit of treatment in the long-term, appropriate use of these therapeutic approaches is essential for patient care. In this review we outline current literature on the use of anti-osteoporotic drugs in β-TM patients with osteoporosis focusing on data on the efficacy, safety, and duration of treatment. In addition, we propose a long-term management plan for β-TM -associated osteoporosis aiming at the optimal patient care for this special population.

Background: Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0-14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA)., Methods: A total of 3966 WT cases (0-14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990-2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990-2012); mortality data were provided by the respective national statistical services. Kaplan-Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS)., Results: Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR] 5-year increment :0.67, 95% confidence interval [CI]:0.60, 0.75) vs. a non-significant 10% improvement in the SEER data, which had a high starting value. OS differentials [two-fold less favourable among children aged 10-14 years, boys and those living in rural SEE areas (HR:1.37; CI:1.10-1.71) or countries with inferior HDI (2-3-fold)] were minimal in the USA., Conclusions: Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Despite advances in the management of nephroblastoma (Wilms' tumor, WT), the etiology of the tumor remains obscure. We aimed to compare nephroblastoma incidence rates and time trends among children (0-14 years) in 12 Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology, and End Results Program (SEER), USA, in relation to the human development index (HDI)., Methods: In total 1776 WT cases were recorded in 13 SEE collaborating registries (circa 1990-2016), whereas data on 2260 cases (1990-2012) were extracted from the SEER database. Age-standardized incidence rates (AIRs) were calculated and correlated with HDI, whereas temporal trends were evaluated using Poisson regression and Joinpoint analyses., Results: The overall SEE AIR (9.2/10 6 ) was marginally higher than that of the SEER (8.3/10 6 ), whereas significant differences were noted among the 13 SEE registries which comprised mainly Caucasian populations. A statistically significant temporal increase in incidence was noted only in Belarus. Most cases (∼75%) were diagnosed before the fifth year of life, with rates steadily declining thereafter; median age at diagnosis was similar in SEE countries and SEER. A slight male preponderance in the first year of life (male:female = 1.1) was followed by a female preponderance in the older age groups (male:female = 0.7). Lastly, a statistically significant positive association between higher HDI and increasing nephroblastoma incidence was noted (regression coefficient: +3.25, 95%CI: +1.35, +5.15)., Conclusions: Variations in incidence and time trends across the examined registries, changing male-to-female patterns with advancement in age, and positive associations with the HDI imply a plausible role for environmental and genetic factors in disease etiology, and these need to be explored further., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Bone changes are a prominent symptom of beta-thalassemias, related to expansion of bone marrow and reduction of bone density. Conventional treatment ameliorates bone changes and improves survival, thus increasing the morbidity of bone diseases in adulthood. Peripheral quantitative computer tomography (pQCT) was used recently to assess the changes in volumetric bone mineral density (vBMD) in various bone compartments., Objectives: Assessment of indices of bone density and structure in patients with thalassemia major (thal-major) and intermedia (thal-interm) on conventional therapy and in healthy adults., Material and Methods: 45 patients with thal-major, 27 with thal-interm and 32 healthy individuals aged 21-42 years were studied by pQCT analysis. The vBMD total (tot), trabecular (trab) and cortical (cort), the bone mineral content (BMC), the cross sectional area (CSA), the cortical thickness (CRTHK) and the stress strain index (SSI) were assessed at the 4% site of the distal radius., Results: Tot, trab, and cort vBMD, BMC, and cortical thickness showed statistically significant differences among the three groups with significant reduction in thalassemics. No significant differences were found in the three groups with CSA and SSI. Impairment of bone density and structure in Greek thalassemics on proper treatment was not as severe as expected. A significant proportion of patients had bone density indices within the normal range and above the 10th percentile of normal., Conclusions: Peripheral QCT analysis is a convenient method to study the regional changes of bone density in patients with thalassemia. These changes affect mainly the cortical compartment and are more pronounced in thalassemia intermedia.

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency, autoimmune hemolytic anemia, and by a complex of neurologic manifestations including ataxia, developmental delay, and spasticity. PNP protein catalyzes the phosphorolysis of deoxyinosine and deoxyguanosine. It is found in most tissues of the body but is expressed at the highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. We describe a five-yr-old boy with muscular hypertonia, impaired growth, autoimmune hemolytic anemia, and neutropenia who underwent HSCT from his HLA-identical sister. One yr post-HSCT, the boy developed normal immunological functions, and his neurological status improved.

Hypocalcemia, hyperparathyroidism, hypovitaminosis D, hypocalcitoninemia and decreased bone mass are side effects of several anticonvulsant drugs. Since calcitonin inhibits the mineral mobilization of bone and augments minerals bone content, combined therapy with calcitonin, calcium, vitamin-C and vitamin-D was administrated to a patient with severe anticonvulsant disturbances of bone metabolism. Calcitonin hypersensitivity was evident. The symptomatology, characterized by the rare hypocalcemic hyperpyrexia, regressed after calcium infusion.