Adverse Effects of Total Body Irradiation: A Two-Decade, Single Institution Analysis

Pearlman, R.; Hanna, Renee; Burmeister, Jay; Abrams, Judith; Dominello, M.M.

doi:10.1016/j.adro.2021.100723

Cited by 16 publications

(13 citation statements)

References 35 publications

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“…It has been reported that TBI is associated with an increased risk of late effects. 5 , 43 However, in our study, we did not find a higher incidence of late effects in the TBI-Cy than BuCy groups, which is contrary to previous reports. 5 , 43 The reasonable explanation may be that TBI dose in our study was not as high as those in other reports 5 , 43 and there was an insufficient follow-up period to observe more late effects onset.…”

Section: Discussioncontrasting

confidence: 99%

“… 5 , 43 However, in our study, we did not find a higher incidence of late effects in the TBI-Cy than BuCy groups, which is contrary to previous reports. 5 , 43 The reasonable explanation may be that TBI dose in our study was not as high as those in other reports 5 , 43 and there was an insufficient follow-up period to observe more late effects onset. Furthermore, a low dose rate of < 0.06 Gy/min was used in our study, which might decrease the incidence of late effects such as interstitial pneumonitis and cataracts.…”

Section: Discussioncontrasting

confidence: 99%

“… 4 However, TBI-based regimens are associated with serious lifelong adverse events (AEs), including interstitial pneumonia, cataracts, endocrine disturbances, and secondary malignancies. 5 Over the past few decades, intravenous busulfan (Bu) is introduced as the conditioning for allo-HSCT. Retrospective and perspective studies of myeloid malignancies reveal that Bu-based regimens gave noninferior or even superior survival.…”

Section: Introductionmentioning

confidence: 99%

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Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial

Zhang

Huang

et al. 2023

JCO

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PURPOSE It remains controversial whether busulfan-based versus total body irradiation (TBI)–based regimens have comparable outcomes in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We investigated the efficacy and toxicity of busulfan plus cyclophosphamide (BuCy) and TBI plus cyclophosphamide (TBI-Cy) conditioning in allo-HSCT for adult standard-risk B-cell-ALL in first complete remission (CR1). PATIENTS AND METHODS We performed an open-label, randomized phase III trial at 13 hospitals in China. Eligible patients (age 14-65 years) had standard-risk ALL in CR1. Patients were randomly assigned (1:1) to BuCy (0.8 mg/kg four times per day on days –7 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2) or TBI-Cy (4.5 Gy TBI on days –5 to –4 and cyclophosphamide 60 mg/kg once daily on days –3 to –2). The primary end point was 2-year overall survival. Analysis was per protocol. This trial is registered with ClinicalTrials.gov (identifier: NCT02670252 ) and is complete. RESULTS Between January 2016 and February 2020, 275 patients were assigned to receive BuCy (273 assessed) and 275 to TBI-Cy (272 assessed). The 2-year overall survival was 76.6% (95% CI, 71.7 to 81.8) and 79.4% (74.7 to 84.4; P = .457; difference 2.9%; 95% CI, –4.1 to 9.8; P = .022), indicating noninferiority of BuCy. The 2-year relapse was 20.2% (95% CI, 15.6 to 25.1) and 18.4% (14.0 to 23.2; P = .616), and the nonrelapse mortality was 11.0% (95% CI, 7.6 to 15.0) and 11.0% (7.7 to 15.1; P = .988) in the BuCy and TBI-Cy groups, respectively. There were no differences in regimen-related toxicity, graft-versus-host disease, or late effects between the two groups. CONCLUSION The BuCy regimen has noninferior efficiency and safety as TBI-Cy (4.5 Gy × 2) for patients with adult standard-risk B cell-ALL in CR1 undergoing HLA-matched allo-HSCT.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial

Zhang

Huang

et al. 2023

JCO

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“…Several cancer treatments are associated with hematological complications including bone marrow suppression, and reduction in hematopoietic progenitor cells. This results in anemia, neutropenia, and a higher risk of infections [ 98 , 99 ]. Gut microbiota-derived SCFAs have been found to modulate hematopoiesis in the bone marrow to regulate inflammation in different body sites [ 100 ].…”

Section: Scfas and Cancer Treatment Toxicitiesmentioning

confidence: 99%

Gut Microbiota-Derived Short-Chain Fatty Acids: Impact on Cancer Treatment Response and Toxicities

et al. 2022

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The gut microbiota has emerged as a key modulator of cancer treatment responses in terms of both efficacy and toxicity. This effect is clearly mediated by processes impacting the activation and modulation of immune responses. More recently, the ability to regulate chemotherapeutic drug metabolism has also emerged as a key driver of response, although the direct mechanisms have yet to be fully elucidated. Through fermentation, the gut microbiota can produce several types of metabolites, including short-chain fatty acids (SCFAs). SCFAs play an important role in maintaining epithelial barrier functions and intestinal homeostasis, with recent work suggesting that SCFAs can modulate response to cancer treatments and influence both anti-tumor immune response and inflammatory-related side effects. In this review, we will discuss the importance of SCFAs and their implications for cancer treatment response and toxicities.

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“…Differences in biologically effective dose can arise from differences in dose rate, number of fractions and dose per fraction ( 33 ). Despite evidence of dose-dependent antileukemic activity of TBI, more intense dosing is challenging given increases in toxicity and long-term morbidities ( 34 ).…”

Section: Role Of Escalation Of Conditioning Intensity and Chemotherap...mentioning

confidence: 99%

Role of Radiation Based Conditioning Regimens in Patients With High-Risk AML Undergoing Allogenic Transplantation in Remission or Active Disease and Mechanisms of Post-Transplant Relapse

Salhotra

Stein

2022

Front. Oncol.

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In the two decades there has been a consistent improvement in the clinical outcomes of patients diagnosed with acute leukemia undergoing allogenic stem cell transplantation. These improvements have been made possible by advancements in supportive care practices, more precise risk stratification of leukemia patients by genetic testing at diagnosis, accurate disease assessment by measurable residual disease (MRD) in pretransplant marrow and attempts to clear residual disease clones prior to transplant. Availability of targeted therapies, immunotherapies, and approval of novel drug combinations with BCL-2 inhibitors has also improved remission rates for patients who are undergoing transplant. For patients who are unable to achieve a morphologic or MRD- remission prior to transplant, the risk of relapse post-transplant remains high. Total body irradiation (TBI) based intensification of transplant conditioning may be able to overcome risk of increased relapse rate in this clinical setting by improving clearance of leukemic clones. However, in the past increased nonrelapse mortality (NRM) associated with escalation of conditioning intensity has neutralized any potential benefit of decreasing relapse rate in HCT patient resulting in no significant improvement in overall survival. In this review we discuss incorporation of newer radiation techniques such as total marrow irradiation (TMI) to safely deliver targeted doses of radiation at higher doses to improve outcomes of patients with active leukemia. We also discuss the mechanisms associated with leukemia relapse and treatment options available in post allo-HCT relapse setting despite use of intensified conditioning regimens.

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Adverse Effects of Total Body Irradiation: A Two-Decade, Single Institution Analysis

Cited by 16 publications

References 35 publications

Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial

Busulfan Plus Cyclophosphamide Versus Total Body Irradiation Plus Cyclophosphamide for Adults Acute B Lymphoblastic Leukemia: An Open-Label, Multicenter, Phase III Trial

Gut Microbiota-Derived Short-Chain Fatty Acids: Impact on Cancer Treatment Response and Toxicities

Role of Radiation Based Conditioning Regimens in Patients With High-Risk AML Undergoing Allogenic Transplantation in Remission or Active Disease and Mechanisms of Post-Transplant Relapse

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