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

Abstract

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.

Metreleptin worked in a diabetic woman with a history of hematopoietic stem cell transplantation (HSCT) during infancy: further support for the concept of ‘HSCT-associated lipodystrophy’

“…However, it is acceptable that some potential factors may expedite the impact of TBI. These include chemotherapeutic agents used during first-line treatment and/or transplantation preconditioning, cranial or abdominal irradiation [27], endocrinological complications (including hypothyroidism, hypogonadism, and GH deficiency), sarcopenia [5,6], chronic GVHD (especially GVHDrelated scleroderma [7,10]), and immunosuppressants used for GVHD treatment. Among these, GH status may be of particular importance because adults with GH deficiency are at risk of insulin resistance and increased visceral fat, which may temporarily worsen when GH treatment is initiated [28].…”

“…YOUNG ADULTS undergoing hematopoietic stem cell transplantations (HSCT) during childhood are at a high risk of developing diverse metabolic aberrations later in life. These medical conditions include diabetes [1,2], dyslipidemia [3], fatty liver [4], central adiposity [5], and insulin resistance [2,4,6]. Notably, most affected patients have a normal or even low body mass index, differentiating them from obese ones who have overnutrition and/or a sedentary lifestyle [2][3][4][5][6].…”

“…These medical conditions include diabetes [1,2], dyslipidemia [3], fatty liver [4], central adiposity [5], and insulin resistance [2,4,6]. Notably, most affected patients have a normal or even low body mass index, differentiating them from obese ones who have overnutrition and/or a sedentary lifestyle [2][3][4][5][6]. In addition, lipodystrophy of Dunnigan phenotype has sometimes been found among these patients; it is characterized by a loss of subcutaneous adipose tissue in the buttocks and extremities, with lipohypertrophy noted in the cheeks and neck [7][8][9][10].…”

Lipodystrophy as a Late Effect after Stem Cell Transplantation

“…This phenotype is reminiscent of Dunnigan-type lipodystrophy based on mutations in the LMNA gene; however, all patients tested were negative for LMNA mutations, ruling out a potential genetic origin of the disease. Body composition in children and adolescents who received HSCT/TBI has been extensively reviewed recently [ 26 ]. Accordingly, remodeling of adipose tissue is an early event after HSCT, and there is also evidence of reduced muscle mass in children and adolescents after HSCT [ 26 ].…”

“…Body composition in children and adolescents who received HSCT/TBI has been extensively reviewed recently [ 26 ]. Accordingly, remodeling of adipose tissue is an early event after HSCT, and there is also evidence of reduced muscle mass in children and adolescents after HSCT [ 26 ].…”