A Population‐Based Study of Childhood Acute Lymphoblastic Leukemia Diagnosed from July 1981 through June 1985 in the Five Nordic Countries

Gustafsson, Göran; Garwicz, Stanislaw; Hertz, H; Johanesson, G.; Jónmundsson, Guđmundur; Pj, Moe; Salmi, Tuula; Seip, M; Ma, Siimes; Yssing, M.; Åhström, L.

doi:10.1111/j.1651-2227.1987.tb10565.x

Cited by 93 publications

(24 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No specific guidelines were issued then. The first Nordic treatment programme for childhood leukaemia was developed in 1981 (14), and a Nordic register for childhood leukaemia was established the same year. Since 1986, treatment of these malignancies has been uniform in the Nordic countries.…”

Section: Discussionmentioning

confidence: 99%

Late mortality among five-year survivors of cancer in childhood and adolescence Differences between the Nordic Countries

Möller

Garwicz²,

Perfekt³

et al. 2004

Acta Oncologica

View full text Add to dashboard Cite

The present study was aimed at assessing differences between the Nordic countries, if any, in late mortality among five-year survivors of childhood cancer. All cases diagnosed before the age of 20 years, between 1960 and 1989, were collected from all Nordic cancer registries. In total, 13 689 patients were identified as five-year survivors and during the extended follow-up 12.3) of them died. Mortality was analysed by decade of diagnosis, for all sites, and for leukaemia, Hodgkin's lymphoma, and central nervous system tumours separately. Analyses were done within a Cox proportional hazards regression framework with adjustments made for gender and age at diagnosis. Hazard ratios were calculated in relation to a weighted Nordic mean based on the proportion of five-year survivors in each country. Overall late mortality was significantly higher in Denmark and Finland than in Norway and Sweden. This could not be explained by inverse differences in five-year survival. The differences diminished over time and had disappeared in the last period. The pattern was similar for both genders. The disappearance of the differences was most probably the effect of a closer collaboration between Nordic paediatric oncologists with development and implementation of common protocols for treatment of childhood cancers in all countries.

show abstract

Section: Discussionmentioning

confidence: 99%

Late mortality among five-year survivors of cancer in childhood and adolescence Differences between the Nordic Countries

Möller

Garwicz²,

Perfekt³

et al. 2004

Acta Oncologica

View full text Add to dashboard Cite

show abstract

“…7) was treated with GH from age 12 to 14 years. Chemotherapy was given according to the common protocols in the five Nordic countries (Gustafsson et al ., 1987(Gustafsson et al ., , 1998 to patients 7 and 11, and in the remaining patients according to the protocols of the Swedish Child Leukaemia Group ; for both protocols remission was induced with prednisolone and vincristine, and in some patients with doxorubicin and asparaginase. When consolidation therapy was given, it consisted of an intermediate dose of methotrexate, with citrovorum factor rescue, or of cyclophosphamide and cytosine arabinoside.…”

Section: Study Groupmentioning

confidence: 99%

Survivors of childhood acute lymphoblastic leukaemia, with radiation‐induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment

Bülow

Link

Åhrén

et al. 2004

Clinical Endocrinology

View full text Add to dashboard Cite

Summary OBJECTIVE Adult survivors of childhood acute lymphoblastic leukaemia (ALL) often exhibit GH deficiency (GHD), due to prophylactic cranial radiotherapy (CRT). It is not known whether the observed risk for adiposity in these patients is associated with impaired insulin sensitivity and whether the insulin sensitivity is affected by GH replacement therapy. SUBJECTS AND DESIGN Eleven patients with GHD (median age 29 years), previously given prophylactic CRT for ALL, and 11 sex‐, age‐ and body mass index (BMI)‐matched controls were investigated with bioimpedance analysis (BIA) and analysis of serum leptin, serum free fatty acids (FFA) and serum insulin. Insulin sensitivity was measured by a euglycaemic–hyperinsulinaemic clamp technique (IS‐clamp). Moreover, the effects of 12 months of individually titrated GH treatment (median dose 0·5 mg/day) on these parameters were investigated. RESULTS At baseline, the patients had lower fat free mass (FFM) (P = 0·003), higher percentage fat mass (FM) (P = 0·05), serum insulin (P = 0·02) and serum leptin/kg FM (P = 0·01) than controls. The patients had a tendency towards impaired IS‐clamp (P = 0·06), which disappeared after correction for body composition (IS‐clamp/kg FFM; P > 0·5). In the patients, time since CRT was positively correlated with percentage FM (r = 0·70, P = 0·02), and there was an independent negative association between serum FFA and IS‐clamp (P = 0·05). Twelve months of GH treatment increased serum IGF‐I (P = 0·003) and FFM (P = 0·02) and decreased percentage FM (P = 0·03), but no significant changes were seen in serum leptin/kg FM, serum FFA, FFA‐clamp, serum insulin or IS‐clamp (all, P ≥ 0·2). CONCLUSIONS Young adult survivors of childhood ALL with GHD had increased fat mass, hyperleptinaemia and impaired insulin sensitivity, which could be a consequence of radiation‐induced impairment of GH secretion or mediated by other hypothalamic dysfunctions, such as leptin resistance or other unknown factors, affected by CRT. Twelve months of individualized GH replacement therapy led to positive effects on body composition, but the hyperleptinaemia, hyperinsulinaemia and the impaired insulin sensitivity remained unchanged.

show abstract

“…Initially, the children were treated according to the protocols of the Swedish Child Leukemia Group (11) and since 1981 according to the common protocols in the five Nordic countries (12,13). Based on prognostic factors, the patients were allocated to different risk groups with varying treatment intensity.…”

Section: Patients and Methods Patientsmentioning

confidence: 99%

Growth Hormone Deficiency Predicts Cardiovascular Risk in Young Adults Treated for Acute Lymphoblastic Leukemia in Childhood

Link

Maaser²,

Garwicz³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

139

176

View full text Add to dashboard Cite

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving longterm survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified.The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19 -32 yr at the time of study) treated with CRT (median 24 Gy, 18 -30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRHarginine test, and patients with a peak GH 3.9 g/liter or greater were further investigated with an additional insulin tolerance test.Significantly higher plasma levels of insulin (P ‫؍‬ 0.002), blood glucose (P ‫؍‬ 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P < 0.05) were recorded among the ALL patients, compared with controls. Furthermore, the serum levels of high-density lipoprotein cholesterol (P ‫؍‬ 0.03) and Apo A1 (P ‫؍‬ 0.005) were significantly lower among the patients. Compared with controls, the patients had higher body mass index and waist to hip ratio, and body composition measured with dual-energy x-ray absorptiometry showed significantly higher fat mass and lower lean mass (P < 0.001). Forty of 44 ALL patients (91%) were considered GH deficient according to the insulin tolerance test and/or the GHRHarginine test, and the rest were considered GH insufficient.In patients, peak GH during GHRH-arginine was significantly negatively correlated to total body fat mass measured with dual-energy x-ray absorptiometry (r ‫؍‬ ؊0.48, P ‫؍‬ 0.001), waist to hip ratio (r ‫؍‬ ؊0.32, P ‫؍‬ 0.03), plasma insulin (r ‫؍‬ ؊0.49, P ‫؍‬ 0.001), and leptin (r ‫؍‬ ؊0.46, P ‫؍‬ 0.002). Moreover, a significantly positive correlation was recorded with highdensity lipoprotein cholesterol (r ‫؍‬ 0.38, P ‫؍‬ 0.012). Using Doppler echocardiography, a marked reduction in cardiac dimensions and performance (ejection fraction P < 0.001 and fractional shortening P ‫؍‬ 0.01), compared with controls, was recorded.In conclusion, at a median 17 yr after treatment with CRT and chemotherapy in former childhood ALL patients, a significant increase in cardiovascul...

show abstract

A Population‐Based Study of Childhood Acute Lymphoblastic Leukemia Diagnosed from July 1981 through June 1985 in the Five Nordic Countries

Cited by 93 publications

References 10 publications

Late mortality among five-year survivors of cancer in childhood and adolescence Differences between the Nordic Countries

Late mortality among five-year survivors of cancer in childhood and adolescence Differences between the Nordic Countries

Survivors of childhood acute lymphoblastic leukaemia, with radiation‐induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment

Growth Hormone Deficiency Predicts Cardiovascular Risk in Young Adults Treated for Acute Lymphoblastic Leukemia in Childhood

Contact Info

Product

Resources

About