Dataset Information

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.

SUBMITTER: Lorenc A

PROVIDER: S-EPMC7473918 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Lorenc Ava A Hamilton-Shield Julian J Perry Rachel R Stevens Michael M

Journal of cancer survivorship : research and practice 20200718 5

<h4>Purpose</h4>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).<h4>Methods</h4>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 HS ...[more]

PMID: 32388841

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Project description:Background and objectivesIntensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT).Patients and methodsThirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617-1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk.ResultsThe mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III-IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients.ConclusionsIMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

Project description:Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy is subject to radiobiological trade-offs between ALL cell destruction, immune and haematopoietic stem cell survival, and various adverse effects in normal tissue. To diminish toxicity, a shift from single-fraction to fractionated TBI has taken place. However, HSCT and TBI are still associated with multiple late sequelae, leaving room for improvement. This review discusses the past developments of TBI and considerations for dose, fractionation and dose-rate, as well as issues regarding TBI setup performance, limitations and possibilities for improvement. TBI is typically delivered using conventional irradiation techniques and centres have locally developed heterogeneous treatment methods and ways to achieve reduced doses in several organs. There are, however, limitations in options to shield organs at risk without compromising the anti-leukaemic and immunosuppressive effects of conventional TBI. Technological improvements in radiotherapy planning and delivery with highly conformal TBI or total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI) have opened the way to investigate the potential reduction of radiotherapy-related toxicities without jeopardising efficacy. The demonstration of the superiority of TBI compared with chemotherapy-only conditioning regimens for event-free and overall survival in the randomised For Omitting Radiation Under Majority age (FORUM) trial in children with high-risk ALL makes exploration of the optimal use of TBI delivery mandatory. Standardisation and comprehensive reporting of conventional TBI techniques as well as cooperation between radiotherapy centres may help to increase the ratio between treatment outcomes and toxicity, and future studies must determine potential added benefit of innovative conformal techniques to ultimately improve quality of life for paediatric ALL patients receiving TBI-conditioned HSCT.

Dataset Information

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

Purpose

Methods

Results

Conclusions

Implications for cancer survivors

Publications

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

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