OBJECTIVES:To generate body mass index (weightaheight 2 (kgam 2 ), BMI) reference values for 0 to 45-y-old Danes and compare these with published European reference values. SUBJECTS: A national sample used to generate the current Danish height and weight reference (29 106 measurements made 1965 ± 1977; age 0 ± 21 y; sample I), and four samples from Copenhagen (3391 measurements made 1981 ± 1985; age 7 ± 45 y; samples II ± III and 2608 measurements made 1991 ± 1994; age 6 ± 45 y; samples IV ± V). DATA ANALYSIS: Using the LMS method, Danish BMI reference values by age and sex were constructed from samples I and II. These were compared with BMI reference values from Sweden (age 6 ± 16 (girls) or 6 ± 19 y (boys)), Germany (6 ± 19 y), UK (0 ± 23 y), and France (0 ± 87 y). Two recently examined but smaller Danish cohorts (samples IV and V) were compared with the reference values to assess the secular trend in BMI.
Depressed left ventricular fractional shortening and left ventricular dilatation were uncommon years after treatment of childhood leukemia when cumulative anthracycline doses were < or = 300 mg/m2.
Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where <70% consensus occurred, the statement was modified and resubmitted for voting. Twenty-seven statements meeting consensus criteria are reported. For HCLGG, statements describing overall therapeutic purpose and indications for biopsy, observation, or treatment aimed at limiting the risk of visual damage and the need for on-going clinical trials were made. Primary surgical resection was not recommended. For DIPG, biopsy was recommended to ascertain biological characteristics to enhance understanding and targeting of treatments, especially in clinical trials. For HGG, biopsy is essential, the World Health Organization classification was recommended; selection of surgical strategy to achieve gross total resection in a single or multistep process should be discussed with the PNMDT and integrated with trials based drug strategies for adjuvant therapies.
Background Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. Methods Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). Results As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3–79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16–49) for all patients. In all patients, the 24-week disease control rate was 73% (95% CI: 54–87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45–100), 56% (95% CI: 38–74), and 85% (95% CI: 71–99), respectively. Median time to response was 1.9 months (range 1.0–3.8 months). Duration of treatment ranged from 1.2–31.3+ months. Treatment-related adverse events were reported for 20 patients, with Grade 3–4 in 3 patients. No new safety signals were identified. Conclusions In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.
Summary:Internal genitalia and uterine blood flow were assessed by ultrasound in 12 females 4.0-10.9 years after total body irradiation and allogeneic bone marrow transplantation for childhood leukaemia or lymphoma. Median age of the participants was 12.7 years (range 6.1-17.6) at bone marrow transplantation and 21.5 years (11.6-25.6) at the follow-up study. At follow-up all had entered puberty and 11/12 females had experienced the menarche. Eight females received sex steroid replacement therapy, three had spontaneous pubertal development and one woman experienced symptoms of estrogen deficiency. Median uterine and ovarian volumes were significantly reduced to ؊2.6 standard deviation scores (SDS) (؊6.3 to ؊0.6), P ؍ 0.002, and ؊2.6 SDS (؊4.8 to ؊0.5), P ؍ 0.002, respectively, compared with normal controls. Follicles were only detectable in two individuals. Uterine blood flow was impaired, as a systolic blood flow could be measured in 6/9 individuals, and a diastolic blood flow in 1/9 females. Our results indicate that the prescribed dosage of hormone replacement therapy, which was sufficient to induce bleeding and suppress other stigmata of premature menopause, was inadequate to generate normal uterine growth. In order to achieve uterine growth higher doses of hormone replacement therapy may be required. Our results confirm pelvic ultrasound as a reliable tool for investigation of internal female genitalia; however, in an infertility setting further tests are indicated. Keywords: BMT; TBI; childhood; uterus; ovary; uterine blood flow During the past two decades allogeneic bone marrow transplantation (BMT) has been used in the treatment of children with relapsed or very high risk leukaemia and lymphoma. Since many of these children become long-term survivors, the late effects of treatment are of major concern. Preparative regimens for BMT, high-dose chemotherapy alone or in combination with total body irradiation (TBI), may cause various endocrine abnormalities, 1-10 and ovarian failure Correspondence: K Holm, Department of Growth and Reproduction, Section 5064, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark Received 26 March 1998; accepted 5 September 1998 resulting in life-long need for sex steroid replacement therapy (HRT) and infertility is common. Recovery of ovarian function occurs especially when preparative regimens do not include TBI, 5-11 and cases of pregnancies resulting in successful deliveries have been reported even when preparative regimens have included TBI. [12][13][14][15][16][17][18][19][20] The progress of assisted reproduction and the availability of oocyte donation has made pregnancy a possibility in women without ovarian function, provided there is normal function of the uterus. However, once pregnancy has been achieved, other problems may occur. In patients treated for solid tumours abdominal irradiation with 20-30 Gy have caused irreversible damage to uterine musculature and blood flow 21 and a high risk of adverse pregnancy outcome, eg low birth weight and increased perinat...
This prospective study focused on risk factors and clinical outcome of pulmonary and cardiac late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated 162 children by pulmonary function tests (PFTs) and cardiac shortening fraction (SF) before allo-HSCT and yearly up to the 5th year of follow-up. The 5-year cumulative incidence of lung and cardiac impairment was 35 (hazard rate=0.03) and 26% (hazard rate=0.06), respectively. Patients presenting abnormal PFTs and SF at last follow-up were 19 and 13%, respectively, with a median Lansky performance status of 90% (70-100). Chronic graft-versus-host disease (c-GVHD) was the major risk factor for reduced lung function in univariate (P=0.02) and multivariate analysis (P=0.02). Total body irradiation (TBI) alone and TBI together with pre-transplant anthracycline administration were significant risk factors for reduced cardiac function in univariate analysis, only (P=0.04 and 0.004, respectively). In conclusion, our prospective study demonstrates an asymptomatic post-allo-HSCT deterioration of pulmonary and cardiac function in some long-term survivors, who had been transplanted in childhood, and thus emphasizes the need for lifelong cardiopulmonary monitoring and the development of new strategies both to reduce pre-transplant cardiotoxic regimens and to treat more efficiently c-GVHD.
The self-reported health of children treated on NOPHO-AML protocols without HSCT was good, and their use of health care services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects.
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