ALBERT

Description: Reduction in bone mineral density (BMD), fractures, altered body composition, deteriorated motor performance and impaired passive ankle dorsiflexion are side-effects of chemotherapy during childhood acute lymphoblastic leukemia (ALL). Because only scarce information is available on the value of regular exercise to prevent these side-effects, we performed a randomized trial to investigate the effects of intervention with an exercise program. At diagnosis 51 ALL patients (median age: 5.4 years) were randomized into a group receiving intervention (including twice-daily high-intensity weight-bearing activities throughout the two-year during treatment period), or a control group receiving standard care. BMD of total body (BMDTB) and lumbar spine (BMDLS) and body composition parameters were measured using dual energy X-ray absorptiometry (DEXA). We measured motor performance with the Bayley Scales of Infant Development and the Movement-ABC, and passive ankle dorsiflexion with a goniometer. The investigators were blinded to the randomization. Repeated measurements analysis (ANOVA) was used. BMD decreased equally in the intervention and control group during treatment (delta-BMDTB: −0.75 SDS vs −0.96 SDS, p=0.65 and delta-BMDLS: −0.15 SDS vs −0.04 SDS, p=0.83), and increased equally during the year after treatment (delta-BMDTB: 0.42 SDS vs 0.35 SDS, p=0.70 and delta-BMDLS: 0.10 SDS vs 0.14 SDS, p=0.84). Body-fat increased during treatment in both groups (delta-fat: 1.04 SDS vs 1.56 SDS, p=0.25). In the intervention group a more rapid decline of body-fat was observed during the year after completion of therapy than in the control group (delta-fat: −1.08 SDS vs −0.49 SDS, p=0.01). Lean body mass (LBM) of both groups decreased equally during treatment (delta-LBM: −0.61 SDS vs −0.12 SDS, p=0.16) and increased equally the year after stop of treatment (delta-LBM: 0.29 SDS vs 0.22 SDS, p=0.66). Both groups showed similar changes in passive ankle dorsiflexion mobility (−5.2º vs −4.6º, p=0.76) and motor performance (0.37 SDS vs 0.68 SDS, p=0.44) during treatment. Adherence to the exercise program varied considerably: 11% of the patients performed exercises daily, 37% more than once a week, 16% once weekly and 36% less than once a week. The exercise program was not more beneficial in preventing reduction in BMD, motor performance and passive ankle dorsiflexion than standard care, most likely due to unsatisfactory compliance. However, the faster recovery after stop of treatment of the excess of body-fat in the intervention group than in the control group may be due to the educational effect of the intervention program.

Description: Abstract 3071 Poster Board III-8 Introduction As the survival of pediatric acute lymphoblastic leukemia (ALL) improves, research on treatment-related morbidity, like disturbance of body composition and bone mineral density (BMD), is required. This study investigates pharmacogenetic risk factors for BMD and body composition in pediatric ALL. Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ ApaI/ TaqI and Cdx-2/ GATA), collagen type I alpha 1 (SpI), estrogen receptor 1 (ESR1: PvuII/ XbaI) and the glucocorticoid receptor (BclI)) on body composition, BMD and fracture risk during dexamethasone-based pediatric ALL treatment. Anthropometry data of 69 patients (mean age 7.4 (range: 1.6-16.8) year) treated according to the DCOG-ALL9 protocol were evaluated. In patients aged 〉4 years body composition and BMD of the total body (BMD-TB) and the lumbar spine (BMD-LS) were measured repeatedly using dual energy X-ray absorptiometry. To correct for bone size we calculated bone mineral apparent density of the lumbar spine (BMAD-LS) with the model BMAD-LS = BMD-LS x (4/ (n × width)). All values were expressed as standard deviation scores (SDS). Repeated measurements analysis (ANOVA) was used. Results Non-carriers of VDR 5'-end (Cdx-2/ GATA) haplotype 3 revealed a significant larger fat gain than carriers (Δ%fat: non-carriers: +1.76 SDS, carriers: +0.77 SDS, p

Description: Introduction: Pediatric acute lymphoblastic leukemia (ALL) and its treatment have adverse effects on growth, bone mineral density (BMD) and body composition. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate and homocysteine metabolism. Several studies showed a higher incidence of methotrexate (MTX) related toxicity among carriers of polymorphisms in the (MTHFR) gene. Methods: We studied whether polymorphisms in the MTHFR gene influence the risk of therapy-induced side effects in pediatric ALL. C677T and A1298C polymorphisms in the MTHFR gene were studied in 83 pediatric ALL patients (47 male, 36 female) using real-time PCR and hybridization probes (LightCycler system). Mean age at diagnosis was 7.5 yr (1.5 – 16.8 yr). All patients were treated with a dexamethasone-based treatment protocol, without cranial irradiation. BMD of lumbar spine (LS) and total body (TB) and body composition were measured using DEXA-scan four times during therapy and once one year after therapy; results are compared with healthy age- and sex-matched controls and expressed as standard deviation scores (SDS). Bone mineral apparent density of the lumbar spine (BMAD) was calculated to correct for bone size. Results: In all patients, lean body mass (LBM) was already reduced at baseline and remained low during therapy, whereas percentage body fat increased during therapy. Height SDS was reduced during therapy and remained low during the first year after therapy. Carriers of the 677 T allele showed a reduced BMDLS as compared to healthy controls both at baseline (SDS −0.81; p

Description: Introdution Symptomatic AVN occurs as a serious complication of treatment in 4%–12.5% of pediatric cases with ALL. The final common pathway for the development of AVN involves a compromise in the blood flow, leading to infarction. The pathogenesis is multifactorial, including elevated intracortical pressure, vascular occlusion, altered lipid metabolism/fat emboli, hemostatic abnormalities and inhibition of angiogenesis. The difference in incidence of AVN in patients treated according to one and the same protocol suggests a genetic variation as a contribution to the biology of AVN. In one report, familial occurence of bone marrow edema syndrome (early phase of AVN) was associated with elevated levels of lipoprotein(a)[Lp(a)]. Lp(a) is a complex of low-density lipoprotein (LDL) and a high molecular weight glycoprotein called apolipoprotein(a)[apo(a)]. The Lp(a) level is inversely correlated with the kringle IV repeat number in apo(a), that is present as a naturally variation in the population. Methods We investigated the Lp(a) levels and the genetic variation in the Apo(a) gene in pediatric patients with and without AVN. DNA from mononuclear cells was isolated from 10 ALL patients with AVN (group I) and 12 patients without AVN (group II), all matched for age, gender and protocol. AVN is defined as pain of the extremities, not related to treatment with vincristine, confirmed by finding typical abnormalities on MRI. The control group consisted of 13 healthy Caucasian subjects (group III). To detect the number of kringle IV repeats pulsed field gel elctrophoresis (PFGE) and Southern blot of genomic DNA was performed. Serum Lp(a) levels were determined by immuno-nefelometric detection method. Results The median number of kringle IV repeats (mean of both alleles) did not significantly differ between the three groups: 25 (range 16–37, group I), 24 (range 13–32, group II), 21 (range 10–36, group III). The median Lp(a) levels in ALL patients with AVN versus ALL patients without AVN were respectively 0.085 g/L (range