Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age

Davis, Nikki; Stewart, Claire E.; Moss, Andrew; Woltersdorf, Wolf; Hunt, Linda; Elson, Ruth; Cornish, Jacqueline; Stevens, Megan; Crowne, Elizabeth

doi:10.1111/cen.12773

Cited by 17 publications

(16 citation statements)

References 42 publications

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“…[2][3][4][5][6][7][8] The causes of impaired physical performance include deficits in cardiopulmonary and musculoskeletal function, which may be related to both the primary treatment and the conditioning regimen before HCT. 3,[8][9][10][11][12][13][14][15] Also, growth hormone (GH) deficiency may develop after HCT 16,17 and may impair muscle strength and physical performance. 18 Impaired physical performance may also be caused by, as well as predispose to, physical inactivity.…”

Section: Introductionmentioning

confidence: 99%

Exercise capacity in young adults after hematopoietic cell transplantation in childhood

Öberg

Genberg

Malinovschi

et al. 2018

American Journal of Transplantation

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A symptom-limited incremental cycle ergometer test was performed in 17 young adult patients treated with hematopoietic cell transplantation and total body irradiation for hematologic malignancies during childhood. These 17 young adult patients were compared with 17 sex- and age-matched healthy control subjects. Assessments of pulmonary function, cardiac function, body composition, and levels of growth hormone were made. The median follow-up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (P < .001). All patients, but only 1 control, failed to achieve a peak workload >80% (P < .001). Fat-free mass was significantly lower (43.5 vs 57.6 kg, P < .001) and fat mass percentage was significantly higher (31.8% vs 24.2%, P = .011) in the patients. The peak workload adjusted for fat-free mass was significantly lower in the patients (3.3 vs 4.3, P < .001). In the patients, peak workload correlated significantly with total lung capacity (r = .54, P = .025). In summary, long-term survivors have significantly decreased exercise capacity compared with healthy individuals. Together with their altered body composition, this may predispose them to cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Exercise capacity in young adults after hematopoietic cell transplantation in childhood

Öberg

Genberg

Malinovschi

et al. 2018

American Journal of Transplantation

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“…A final total of 20 papers were included-seven controlled studies [1,10,[18][19][20][21][22], five uncontrolled studies [23][24][25][26][27] and eight case reports/series [28][29][30][31][32][33][34][35]. Only one study included an intervention [23].…”

Section: Search Resultsmentioning

confidence: 99%

“…Wei et al also found significantly lower BMI and fat mass index, but this was compared to obese controls [10,22]. Three studies found significantly higher body fat: body fat % compared to short stature controls [19] and healthy controls [20] and whole body fat mass z score compared to reference controls [1]. Data from Adachi et al [26] suggests BMI may be lower than leukaemic controls with no TBI, and, although significance could not be tested, within the normal range for age.…”

Section: Total Body Fatmentioning

confidence: 94%

“…Most of the studies which measured central adiposity found significantly higher central adiposity for HSCT + TBI groups compared to leukaemic controls and non-leukaemic (obese/ short stature/healthy) controls. Evidence from four studies found significant differences for lower waist-to-hip ratios and higher android-gynoid fat ratios compared to leukaemic controls and for higher waist circumference/waist-height ratio, greater trunk fat % and visceral fat %, compared to nonobese non-leukaemic controls [1,19,22,118]. One study found evidence of significant differences for lower waist circumference/waist-height ratio, higher visceral fat % and higher visceral fat to total/subcutaneous fat ratios compared to obese non-leukaemic controls [10].…”

Section: Central Adipositymentioning

confidence: 99%

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Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review

et al. 2020

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Purpose To collate evidence of changes in body composition following treatment of leukaemia in children, teenagers and young adults (CTYA, 0-24 years) with allogeneic haematopoietic stem cell transplant and total body irradiation (HSCT+TBI). Methods Papers were identified by searching Medline and Google Scholar, reference lists/citations and contacting key authors, with no date or language restrictions. Inclusion criteria were as follows: leukaemia, HSCT+TBI, aged ≤ 24 years at HSCT and changes in body composition (total fat, central adiposity, adipose tissue function, muscle mass, muscle function). Quality was assessed using a brief Newcastle-Ottawa scale.Results Of 900 papers, 20 were included: seven controlled, five uncontrolled studies and eight case reports. Study quality appeared good. There was little evidence of differences in total fat/weight for HSCT + TBI groups (compared to healthy controls/population norms/short stature controls). There was some evidence of significantly higher central adiposity and differences in adipose tissue function (compared to leukaemic/non-leukaemic controls). Muscle mass was significantly lower (compared to healthy/obese controls). Muscle function results were inconclusive but suggested impairment. Case reports confirmed a lipodystrophic phenotype. Conclusions Early remodelling of adipose tissue and loss of skeletal muscle are evident following HSCT + TBI for CTYA leukaemia, with extreme phenotype of overt lipodystrophy. There is some evidence for reduced muscle effectiveness. Implications for Cancer Survivors Body composition changes in patients after HSCT + TBI are apparent by early adult life and link with the risk of excess cardiometabolic morbidity seen in adult survivors. Interventions to improve muscle and/or adipose function, perhaps utilizing nutritional manipulation and/or targeted activity, should be investigated.

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“…Patient's age was not part of the exclusion criteria as both adult and pediatric patients were included in our analysis. Studies that did not assess the direct association of DM/IGM with TBI or did not have eligible study population were excluded (Chemaitilly et al, 2009;Majhail et al, 2009;Baker et al, 2010;Frisk et al, 2011;Sohn et al, 2011;Bizzarri et al, 2015;Davis et al, 2015;Wei et al, 2015;Wilhelmsson et al, 2015;Wei et al, 2016;Bielorai et al, 2017;Friedman et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis

Poonsombudlert

Limpruttidham

2019

Asian Pac J Cancer Prev

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Objective:Hematopoietic stem cell transplant (HSCT) has recently emerged as a cure for previously “incurable” diseases and is being explored and attempted in many other fields including congenital and acquired non-malignant diseases. However, the long-term side effect associated with HSCT especially Total Body Irradiation (TBI) is still understudied. Therefore, we attempted to establish association between TBI and risk of developing Diabetes Mellitus (DM) or impaired glucose metabolism (IGM).Methods:We searched for titles of articles in MEDLINE (PubMed), EMBASE, and Cochrane library in August 2018 that evaluated the association between TBI in the setting of HSCT and DM or IGM. We conducted a random effect meta-analysis of 11 studies involving a total of 13,191 participants and reported the pooled MD (mean difference) for the development of DM/IGM after TBI as part of the conditioning regimen for HSCT.Results:We found a significant increase in the risk of developing DM/IGM after TBI is used as part of the conditioning regimen compared to other types of conditioning regimen with the pooled MD being 5.42, 95% Confidence Interval (CI) 2.51-11.71, I2=92.4%.Conclusion:TBI as a conditioning regimen in the setting of HSCT significantly increases the risk of developing DM/IGM. Therefore, we recommend close monitoring and screening for diabetes mellitus in patients who underwent TBI before HSCT.

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Growth hormone deficiency after childhood bone marrow transplantation with total body irradiation: interaction with adiposity and age

Abstract: GHD was more prevalent in BMT/TBI survivors than expected for the CRT dose in TBI, worsened with time and persisted into adulthood. GHD could not be explained by adiposity. There was no evidence of GH neurosecretory dysfunction or resistance after BMT/TBI.

Cited by 17 publications

References 42 publications

Exercise capacity in young adults after hematopoietic cell transplantation in childhood

Exercise capacity in young adults after hematopoietic cell transplantation in childhood

Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review

Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis

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