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A comprehensive comparison between TBI vs non-TBI-based conditioning regimen in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis
Ansari, F., Behfar, M., Jafari, L., Mohseni, R., Naji, P., Karamlou, Y., Amirzade-Iranaq, M. H., Hamidieh, A. A.
Leukemia research. 2023;135:107416
Abstract
INTRODUCTION We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric patients (under 18 years old) with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS A systematic search was performed on MEDLINE, Scopus, WOS, and PMC. Also, a search for grey literature was performed on Google Scholar and relevant articles' references were included. Relevant articles which met the inclusion criteria were retrieved up to October 31th, 2022. CMA version 2 was used for the quantitative synthesis of the data. RESULTS Eight studies on efficacy and safety of TBI and non-TBI as a conditioning regimen were analyzed and six comparative studies on late toxicity were investigated. The meta-analysis revealed a hazard ratio (HR) of 1.508 (95% CI 0.96-2.35) for overall survival (OS) in instances of non-TBI conditioning. Also, an HR of 1.503 (95% CI 1.006-2.25) for disease-free- survival (DFS) favoring TBI-based conditioning. Late complications were reported to be significantly higher in the TBI conditioning regimen group than in the non-TBI group. CONCLUSION It appears that non-TBI regimens are as effective as TBI regimens in pediatrics with ALL regarding OS. Occurrence of latent toxicity is higher with TBI conditioning regimen. Conversely, TBI-based regimens are superior to non-TBI conditioning regimens regarding DFS. Considering all aspects, non-TBI conditioning regimens can be an alternative treatment option for pediatric ALL undergoing HSCT.
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Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis
Rehman, M. E. U., Chattaraj, A., Mahboob, A., Ijaz, Z., Franco, D., Farhan, M., Dharma, K., Mumtaz, H., Saeed, S., Basit, J., et al
Clinical lymphoma, myeloma & leukemia. 2023
Abstract
Allogeneic hematopoietic stem cell transplant (HSCT) is indicated in pediatric patients with acute lymphoblastic leukemia (ALL) who have relapsed or are at a very high risk of relapse during first complete remission. Two types of myeloablative conditioning are employed before allogeneic HSCT total body irradiation (TBI)-based regimens and chemotherapy (CHT) alone. This study compares the efficacy and safety of TBI-based regimens and CHT-based conditioning in pediatric, adolescent, and young adult patients with ALL (0-24 years old). TBI-based and CHT-conditioning regimens were evaluated in 4262 and 1367 patients, respectively, from 15 studies. Compared to CHT alone, TBI-based regimens were associated with better overall survival (OS), relative risk (RR) 1.21, better event-free survival (RR 1.34), and a reduced risk of relapse (RR 0.69). Both approaches had comparable risk of acute graft-versus-host disease (GVHD), grades 3 to 4 acute GVHD, chronic GVHD, and nonrelapse mortality (NRM). In the subgroup analysis for patients in first complete remission, TBI-based regimens and CHT alone had comparable OS and NRM. Our results demonstrate the superiority of TBI-based regimens compared to CHT alone in pediatric patients with ALL.
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Pulmonary Toxicity After Total Body Irradiation - Critical Review of the Literature and Recommendations for Toxicity Reporting
Vogel, J., Hui, S., Hua, C. H., Dusenbery, K., Rassiah, P., Kalapurakal, J., Constine, L., Esiashvili, N.
Frontiers in oncology. 2021;11:708906
Abstract
INTRODUCTION Total body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. The most common adverse effect is pulmonary toxicity including idiopathic pneumonia syndrome (IPS). As centers adopt more advanced treatment planning techniques for TBI, total marrow irradiation (TMI), or total marrow and lymphoid irradiation (TMLI) there is a greater need to understand treatment-related risks for IPS for patients treated with conventional TBI. However, definitions of IPS as well as risk factors for IPS remain poorly characterized. In this study, we perform a critical review to further evaluate the literature describing pulmonary outcomes after TBI. MATERIALS AND METHODS A search of publications from 1960-2020 was undertaken in PubMed, Embase, and Cochrane Library. Search terms included "total body irradiation", "whole body radiation", "radiation pneumonias", "interstitial pneumonia", and "bone marrow transplantation". Demographic and treatment-related data was abstracted and evidence quality supporting risk factors for pulmonary toxicity was evaluated. RESULTS Of an initial 119,686 publications, 118 met inclusion criteria. Forty-six (39%) studies included a definition for pulmonary toxicity. A grading scale was provided in 20 studies (17%). In 42% of studies the lungs were shielded to a set mean dose of 800cGy. Fourteen (12%) reported toxicity outcomes by patient age. Reported pulmonary toxicity ranged from 0-71% of patients treated with TBI, and IPS ranged from 1-60%. The most common risk factors for IPS were receipt of a TBI containing regimen, increasing dose rate, and lack of pulmonary shielding. Four studies found an increasing risk of pulmonary toxicity with increasing age. CONCLUSIONS Definitions of IPS as well as demographic and treatment-related risk factors remain poorly characterized in the literature. We recommend routine adoption of the diagnostic workup and the definition of IPS proposed by the American Thoracic Society. Additional study is required to determine differences in clinical and treatment-related risk between pediatric and adult patients. Further study using 3D treatment planning is warranted to enhance dosimetric precision and correlation of dose volume histograms with toxicities.
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Body composition after allogeneic haematopoietic cell transplantation/total body irradiation in children and young people: a restricted systematic review
Lorenc, A., Hamilton-Shield, J., Perry, R., Stevens, M.
Journal of cancer survivorship : research and practice. 2020
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.
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Total Body Irradiation and Risk of Diabetes Mellitus; A Meta-Analysis
Poonsombudlert, K., Limpruttidham, N.
Asian Pacific journal of cancer prevention : APJCP. 2019;20(3):885-891
Abstract
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.