Diencephalic Syndrome: Misleading Clinical Onset of Low-Grade Glioma.

BACKGROUND: Diencephalic Syndrome is an atypical early manifestation of low-grade gliomas; so, it is important to detect it in patients that experience a failure to thrive despite adequate length growth and food intake. The purpose of this article is to focus attention on this rare but potentially dangerous cause of poor weight gain or stunting in childhood. MATERIALS AND METHODS: We describe four patients with Diencephalic Syndrome and low-grade gliomas who were evaluated in our institution from January 2017 to December 2021. CASE DESCRIPTION AND RESULTS: two patients presented with suspected malabsorption, and two presented with a suspected eating disorder. In all cases, neurological symptoms appeared late, explaining the reason for the diagnostic delay, which impacts negatively on prognosis and on quality of life. Currently, patients 1 and 2 have stable disease in second-line therapy, patient 3 has stable disease post end of second-line therapy, and patient 4 has stable disease in first-line therapy. Everyone is in psychophysical rehabilitation. CONCLUSIONS: A multidisciplinary evaluation is essential in order to make an early diagnosis and improve prognosis and quality of life.

New Insights into Iron Deficiency Anemia in Children: A Practical Review.

Iron deficiency anemia (IDA) is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39 and 48.1% in developing countries). Although IDA has been recognized for a long time, there are still uncovered issues and room for improving the management of this condition. New frontiers regarding its diagnosis and therapeutic options emerge every day; recently, innovative formulations of iron have been launched, both for oral and parenteral administration, with the aim of offering treatment schedules with higher efficacy and lower toxicity. As a matter of fact, glycinate and liposomal preparations, while maintaining a satisfying efficacy profile, have significantly fewer side effects, in comparison to the traditional elemental iron salts; parenteral iron, usually considered a second-choice therapy reserved to selected cases, may evolve further, as a consequence of the production of molecules with an interesting clinical profile such as ferrocarboxymaltose, which is already available for adolescents aged >14 years. The present article reports the clinically relevant latest insights regarding IDA in children and offers a practical guide to help pediatricians, particularly to choose the most appropriate prevention and therapy strategies.

Monitoring oral iron therapy in children with iron deficiency anemia: an observational, prospective, multicenter study of AIEOP patients (Associazione Italiana Emato-Oncologia Pediatrica).

Oral ferrous salts are standard treatment for children with iron deficiency anemia (IDA). The objective of our study was to monitor oral iron therapy in children, aged 3 months-12 years, with IDA. We prospectively collected clinical and hematological data of children with IDA, from 15 AIEOP (Associazione Italiana di Ematologia ed. Oncologia Pediatrica) centers. Response was measured by the increase of Hb from baseline. Of the 107 analyzed patients, 18 received ferrous gluconate/sulfate 2 mg/kg (ferrous 2), 7 ferrous gluconate/sulfate 4 mg/kg (ferrous 4), 7 ferric iron salts 2 mg/kg (ferric), 62 bis-glycinate iron 0.45 mg/kg (glycinate), and 13 liposomal iron 0.7-1.4 mg/kg (liposomal). Increase in reticulocytes was evident at 3 days, while Hb increase appeared at 2 weeks. Gain of Hb at 2 and 8 weeks revealed a higher median increase in both ferrous 2 and ferrous 4 groups. Gastro-intestinal side effects were reported in 16% (ferrous 2), 14% (ferrous 4), 6% (glycinate), and 0 (ferric and liposomal) patients. The reticulocyte counts significantly increased after 3 days from the start of oral iron supplementation. Bis-glycinate iron formulation had a good efficacy/safety profile and offers an acceptable alternative to ferrous iron preparations.

HbS/ß+ thalassemia: Really a mild disease? A National survey from the AIEOP Sickle Cell Disease Study Group with genotype-phenotype correlation.

OBJECTIVES: HbS/ß+ patients' presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/ß+ patients, with genotype-phenotype correlation, in order to offer guidance for clinical management of such patients. METHODS: Retrospective cohort study of HbS/ß+ patients among 15 AIEOP Centres. RESULTS: A total of 41 molecularly confirmed S/ß+ patients were enrolled (1-55 years, median 10.9) and classified on ß+ mutation: IVS-I-110, IVS-I-6, promoter, and "others." Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS-I-110 group presented the lowest median age at first SCD-related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS-I-6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. CONCLUSIONS: HbS/ß+ is not always a mild disease. Patients with IVS-I-110 mutation could benefit from a standard of care like SS and S/ß° patients. Standardization of treatment is needed.

General anesthesia, conscious sedation, or nothing: Decision-making by children during painful procedures.

BACKGROUND: Following diagnosis, children with cancer suddenly find themselves in an unknown world where unfamiliar adults make all the important decisions. Children typically experience increasing levels of anxiety with repeated invasive procedures and do not adapt to the discomfort. The aim of the present study is to explore the possibility of asking children directly about their medical support preferences during invasive procedures. PROCEDURE: Each patient was offered a choice of medical support on the day of the procedure, specifically general anesthesia (GA), conscious sedation (CS), or nothing. An ad hoc assessment tool was prepared in order to measure child discomfort before, during, and after each procedure, and caregiver adequacy was measured. Both instruments were completed at each procedure by the attending psychologist. RESULTS: We monitored 247 consecutive invasive procedures in 85 children and found that children in the 4 to 7 year age group showed significantly higher distress levels. GA was chosen 66 times (26.7%), CS was chosen 97 times (39.3%), and nothing was chosen 5 times and exclusively by adolescents. The child did not choose in 79 procedures (32%). The selection of medical support differed between age groups and distress level was reduced at succeeding procedures. CONCLUSIONS: Offering children the choice of medical support during invasive procedures allows for tailored support based on individual needs and is an effective modality to return active control to young patients, limiting the emotional trauma of cancer and treatment.

Triptorelin for Fertility Preservation in Adolescents Treated With Chemotherapy for Cancer.

BACKGROUND: Triptorelin, a gonadotropin releasing hormone analogue, can be administered to postpubertal female individuals with cancer who receive chemotherapy to obtain menstrual suppression and decrease the risk of hemorrhage caused by thrombocytopenia. Our goal was to assess whether triptorelin also has a protective role against the gonadotoxicity of chemotherapy. PATIENTS AND METHODS: This retrospective observational study includes all postmenarchal female patients who presented to our Unit from 2000 to 2015 and received chemotherapy for cancer. They were administered depot triptorelin. We evaluated long-term ovarian function in order to detect clinical signs of ovarian damage, miscarriages, and pregnancies. Laboratory follow-up consisted in dosing serum follicle stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone. Ultrasound of the ovaries was performed as well. RESULTS: Of 36 evaluable patients, 9 received hematopoietic stem cell transplantation (HSCT). The remaining 27 patients maintained normal ovarian function at clinical, laboratory, and ultrasound assessment. Five of them achieved spontaneous physiological pregnancy. Four of the 9 patients who underwent HSCT developed premature ovarian failure. CONCLUSION: Our study suggests that gonadotropin releasing hormone-a administered during chemotherapy can prevent premature ovarian failure in patients treated without HSCT and that it is not enough to preserve the ovarian function during HSCT. Hence, a prospective randomized trial with a larger population would be recommended.

Successful Treatment of a Very Late Isolated Relapse in an Adolescent With a PICALM-MLLT10 Positive T-lineage Acute Lymphoblastic Leukemia.

T-lineage ALL is an aggressive disease that needs to be treated with intensive treatment schedules. A late relapse rarely occurs and a clear choice for second-line treatment is on debate. We report on a young adult with a very late isolated extramedullary relapse of PICALM-MLLT10 positive T-ALL, successfully treated with a chemotherapy-based and radiotherapy-based pediatric protocol. We demonstrate that relapse can occur in T-ALL although a SR-MRD behavior treated with a high-risk protocol; specific molecular diagnostic aberrations, as PICALM-MLLT10, are still conserved at very late relapse; a second-line treatment based on pediatric protocol can be effective.

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

BACKGROUND: The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. POPULATION AND METHODS: The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. RESULTS: Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sß°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sß° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5 g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5 mg/kg, and dose at full regimen was 17.1 mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sß° patients. Only 10% started HU before 3 years. In 92%, 500 mg capsule was used; in 6%, the galenic was used; and in 2%, 100 mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sß° patients and a trend toward improvement for SC/Sß+ patients was also observed. CONCLUSIONS: HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants.

Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association.

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

Organizing national responses for rare blood disorders: the Italian experience with sickle cell disease in childhood.

BACKGROUND: Sickle cell disease (SCD) is the most frequent hemoglobinopathy worldwide but remains a rare blood disorder in most western countries. Recommendations for standard of care have been produced in the United States, the United Kingdom and France, where this disease is relatively frequent because of earlier immigration from Africa. These recommendations have changed the clinical course of SCD but can be difficult to apply in other contexts. The Italian Association of Pediatric Hematology Oncology (AIEOP) decided to develop a common national response to the rising number of SCD patients in Italy with the following objectives: 1) to create a national working group focused on pediatric SCD, and 2) to develop tailored guidelines for the management of SCD that could be accessed and practiced by those involved in the care of children with SCD in Italy. METHODS: Guidelines, adapted to the Italian social context and health system, were developed by 22 pediatric hematologists representing 54 AIEOP centers across Italy. The group met five times for a total of 128 hours in 22 months; documents and opinions were circulated via web. RESULTS: Recommendations regarding the prevention and treatment of the most relevant complications of SCD in childhood adapted to the Italian context and health system were produced. CONCLUSIONS: Creating a network of physicians involved in the day-to-day care of children with SCD is feasible in a country where it remains rare. Providing hematologists, primary and secondary care physicians, and caregivers across the country with web-based guidelines for the management of SCD tailored to the Italian context is the first step in building a sustainable response to a rare but emerging childhood blood disorder and in implementing the World Health Organization's suggestion "to design (and) implement … comprehensive national integrated programs for the prevention and management of SCD".

Lessons learned from the H1N1 pandemic: the need to improve systematic vaccination in Sickle Cell Disease children. A multi center survey in Italy.

During the recent H1N1 pandemic, children with Sickle Cell Disease (SCD) experienced more hospitalizations and more complications than the general pediatric population. We performed a retrospective multicenter survey at 9 Pediatric Haematology-Oncology Units across Italy. H1N1 admission rate was 5.2%, with all admissions occurring before vaccine availability. Length Of Stay (LOS) was 6.06 days (7.85 for Acute Chest Syndrome), longer than in other countries. Vaccination coverage was not homogeneous, ranging from 0 to 99%; several family-related and health-system related barriers in accessing vaccinations were identified that should be ameliorated to improve coverage in this high risk group of children.

Craniofacial morphology in patients with sickle cell disease: a cephalometric analysis.

The aim of the study was to evaluate the craniofacial morphology in Caucasian patients with sickle cell disease (SCD) by comparing them with a healthy group paired for gender and age, by means of lateral cephalometric radiographs. Thirty-six Sicilian patients with SCD (17 females and 19 males), including 14 beta(s)beta(s) (mean age 28 +/- 5.9 years), 13 beta(s)beta(0 th) (mean age 27.5 +/- 8 years), and nine beta(s)beta(+th) (mean age 32.8 +/- 9.9 years) were examined. The control group consisted of 36 subjects (mean age 28.9 +/- 8 years) without recognized haematological abnormalities. The means and standard deviations were calculated for each cephalometric variable. A two-sample t-test was used to compare the means between the study and control groups. One-way analysis of variance and Dunnet's multiple comparison test were used in order to analyse the differences between the control group and the subgroups divided according to genotype. The level of significance used was P<0.05. The cephalometric findings indicated a posterior rotation of the mandible and a tendency towards a vertical pattern (clockwise), with lower (P=0.000) and total (P=0.002) face heights increased in comparison with the control sample. These findings were more pronounced in subjects with SCD (beta(s)beta(s)). In all patients, there was a significantly greater maxillary incisor proclination than in the control group. The upper first molar position to the PTV line was significantly increased but only in patients with compound heterozygosis beta(s)beta(th). The SCD patients did not exhibit the craniofacial abnormalities noted in black American patients with SCD; the craniofacial features observed, reflecting the degree of clinical expression of SCD in Sicilian patients, were of moderate severity.

Evidence for the molecular heterogeneity of sickle cell anemia chromosomes bearing the betaS/Benin haplotype.

There are at least four distinct African and one Asian chromosomal backgrounds (haplotypes) on which the sickle cell mutation has arisen. Additionally, previous data suggest that the beta(S)/Bantu haplotype is heterogeneous at the molecular level. Here, we report the presence of the (A)gamma -499 T-->A variation in sickle cell anemia chromosomes of Sicilian and North African origin bearing the beta(S)/Benin haplotype. Being absent from North American beta(S)/Benin chromosomes, which were studied previously, this variation is indicative for the molecular heterogeneity of the beta(S)/Benin haplotype.