Extreme Heterogeneity Of Myeloablative Total Body Irradiation (TBI) Techniques Across Europe: A Survey Of Acute Leukemia Working Party Of The EBMT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4565-4565
Author(s):  
Sebastian Giebel ◽  
Leszek Miszczyk ◽  
Krzysztof Slosarek ◽  
Leila Moukhtari ◽  
Fabio Ciceri ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Conflicts Of Interest ◽  
Working Party ◽  
Treatment Modalities ◽  
In Vivo Dosimetry ◽  
Treatment Unit ◽  
Hematopoietic Stem ◽  
Total Body ◽  
Methodological Aspects

Background Total body irradiation (TBI) is widely used for conditioning prior to both allogeneic and autologous hematopoietic stem cell transplantation. Myeloablatitve doses of TBI are considered highly effective but also associated with relevant toxicity. Both, the efficacy and toxicity may depend on many methodological aspects of TBI. The goal of the survey was to explore current practice across centers collaborating in the European Group for Blood and Marrow Transplantation (EBMT). Methods The questionnaire sent to all EBMT centers included 19 questions regarding the doses used for myeloabaltive TBI, the way of fractionation, the modes of delivering the dose, type of immobilization, methods of dosimetry and organ shielding. 56 centers from 23 countries responded. Results All centers differ with regard at least one of the methodological aspects. The total dose of TBI used for myeloablative transplantation ranges from 8 to 14.4 Gy, the number of fractions ranges from 1 to 8, while the dose per fraction is 1.65 – 8 Gy. Altogether 16 modalities of dosing/fractionation have been identified with 6 x 2 Gy being the most frequent one (n=36, 64%). The dose rate in the axis of the beam ranges from 4.5 – 30 cGy/min (27 modalities; most frequently 18 cGy/min, 5%). The treatment unit is regular linac (n=51, 91%) or cobalt unit (n=5, 9%). Beams used for regular linac are 6 to 23 MV (most frequently 6 MV, n=26, 51%). The most frequent technique used for irradiation is “patient in one field” using two fields per fraction and two patient positions per fraction (n=36, 64%), however, altogether 11 modalities were described with regard to the technique, number of fields and positions per fraction. Source to surface distance is 2 to 5 m (most frequently 4 m; n=10, 18%). In 23 (41%) centers patients are immobilized during TBI, using 9 different types of device. Fifty-two centers (93%) measure acquired dose of irradiation using 5 types of detectors for in vivo dosimetry (most frequently semiconductors; n=37, 66%). Accepted discrepancy between planned and measured dose ranges from 1.5 to 10%. In 47 (84%) centers lungs are shielded during irradiation and lung density is considered for treatment planning. Maximum accepted dose for lungs ranges from 6 to 12 Gy. Additionally, in some centers lenses (14%), thyroid gland (7%), larynx (4%), kidneys (4%) and/or salivary glands (2%) are shielded. Conclusions TBI is an extremely heterogeneous treatment modality. Differences between centers regard all methodological aspects. Our findings should warrant caution in interpretation of clinical studies involving TBI. Further investigation is needed to evaluate whether differences between treatment modalities influence the efficacy and safety of the TBI procedure. Finally, efforts to standardize the method should be considered. Disclosures: No relevant conflicts of interest to declare.

Field Junction Technique for Helical Tomotherapy-Based Total Body Irradiation

2018 ◽  
Vol 63 (2) ◽  
pp. 55-61
Author(s):  
А. Логинова ◽  
A. Loginova ◽  
Д. Товмасян ◽  
D. Tovmasyan ◽  
А. Черняев ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Dose Distribution ◽  
Helical Tomotherapy ◽  
In Vivo Dosimetry ◽  
Hematopoietic Stem ◽  
Junction Area ◽  
In Vivo Measurements ◽  
Total Body ◽  
Field Junction

Purpose: Combination of total body irradiation (TBI) with chemotherapy is widely used technique for conditioning before hematopoietic stem cell transplantation for patient with hematological malignancies worldwide. Total body irradiation for patients with high height has to be divided into two parts: irradiation of upper part of the patient’s body (including head, body and part of legs) and irradiation of lower part of the patient’s body (including leg). There is an area in which the fields overlap each other – the junction area. The aim of this work is the development and verification of simple junction technique that would provide the dose distribution in the junction area from 90 to 125 % of prescribed dose. Material and methods: Total body irradiation was performed on the Tomotherapy machine using helical geometry of the beam delivery. Distribution of the dose in junction area was investigated. Simple solution was proposed: during the optimization of the radiotherapy plan certain margin should be maintained between upper and lower targets while dose distribution in junction area satisfies the uniformity requirements for the given irradiation geometry. The dimension of the margin was determined experimentally using a CheesePhantom and radiochromic EBT-2 films. The uniformity of dose distribution in the junction area was monitored by in vivo measurements using radiochromic EBT-2 films located on the skin surface of patients. Results: The dimension of the margin at which the dose in the junction area is within the range of 90 to 125 % of the prescribed dose was determined experimentally and amounted to 5.25 cm. The values of the measured dose were in the range from 97 to 105 %. In total 18 in vivo measurements of the junction area were performed. According to the results of in vivo dosimetry, the values of the doses measured in the junction area were in the range from 93 ± 3 % to 108 ± 4 %. Conclusion:The developed planning method with the selected plan geometry ensures satisfactory heterogeneity of the dose distribution in the area of field junction between the upper and lower irradiation regions, despite of the existing uncertainty of patient positioning. Results were confirmed by in vivo measurements. The obtained data can be used for total body irradiation of the patients using Helical Tomotherapy.

SU-E-T-85: Total Body Irradiation (TBI) Optically Stimulated Luminescence In Vivo Dosimetry

2013 ◽  
Vol 40 (6Part11) ◽  
pp. 223-223 ◽  
Author(s):  
C Holloway ◽  
S Mahendra ◽  
D Kaurin ◽  
L Sweeney
Keyword(s):  
Total Body Irradiation ◽  
Optically Stimulated Luminescence ◽  
In Vivo Dosimetry ◽  
Total Body

Rituximab In Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Chronic Lymphocytic Leukemia with Fludarabine + Total Body Irradiation Conditioning: Results of a Phase II Prospective Multicenter Study (ITAC 02-02)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3520-3520
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Mohamad Mohty ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Median Time ◽  
Total Body Irradiation ◽  
Cumulative Incidence ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Positive Trend ◽  
Hematopoietic Stem ◽  
Total Body

Abstract Abstract 3520 Background: CLL remains incurable with standard therapies. Myeloablative allogeneic SCT (allo-HSCT) is still associated with high TRM and few late relapses. Recently, the major focus of transplantation in CLL has been with reduced-intensity conditioning (RIC) allo-HSCT, which is applicable to the more elderly patient population and which attempts to exploit the graft-versus-leukemia (GVL) effect that was proved in CLL Objective: To evaluate the efficacy and toxicity a RIC regimen including fludarabine and total body irradiation (TBI) with the introduction of rituximab for allo-HSCT in patients with a CLL stage B or C diagnosis. Materials and methods: This prospective study included adult CLL patients with age < 65 years in stage B or C in response after a salvage treatment either following at least 2 treatment lines (1 including fludarabine) or after a progressive disease after auto-HSCT, having a HLA identical sibling donor and a good performance status (Karnfosky >70%). Donors were mobilized by G-CSF and in case of collection failure, bone marrow aspiration was authorized. The conditioning included: rituximab 375mg/m2 on day -5, fludarabine 30 mg/m2 from day-4 to day-2, TBI 2grays (6-7 cGrays/minute) on day 0 and rituximab 500mg/m2 on day1 and day8. GVHD prophylaxis used cyclosporine A (IV 3mg/kg/day) from day-2 and mycomofetil fenolate oral (2g/day) from day 1. Results: Between April 2003 and December 2008, 40 patients were included, 34 (85%) males and 6 females with a median age of 54 years (35-65), 38 (95%) were in B stage at diagnosis and 2 in stage C. Among 23 explored for cytogenetics, 8 were abnormal (3 del17, 1 trisomy12, 1 t(8-11) & 1 del13). Before transplantation, 17 patients received 2 lines treatment, 10 three lines, 5 four lines, and 8>4. Only 1 patient received a previous auto-HSCT. Among 18 explored for Matutes status, 1 was in score 1, 1 in score 2, 3 in score 3, 5 in score 4 & 9 in score 5. At time of allograft, 7 (17%) patients were in complete response (CR), 29 (73%) in partial response (PR) and 4 (10%) < PR. For sex-matching, 59% were mismatched (27%of them were F>M). For ABO matching, 68% were compatible, 19% major incomp. & 13% minor incopm. The median interval diagnosis-allo-HSCT was 58 months (6-177). Median CD34+ number was 7.64 (3.1-18.7). Seven (17%) patients did not receive rituximab during conditioning because the protocol did not include it at the beginning and has been amended later. Thirty-nine (98%) patients engrafted with a median time to neutrophils recovery of 20 days (11-70), 79% of patients reached a total donor chimerism at day 90. Seventeen patients developed aGVHD grade ≥II (8 grII, 8 grIII & 1 grIV) with a cumulative incidence at 3 months of 44% (36-52). The cumulative incidence of cGVHD was, at 12 months: 29% (21-36) for limited and extensive; at 18 months: 32% (24-40) limited and 42% (34-50) extensive. After a median follow-up of 28 months (3-71), the median OS was not reached with 3 and 5-years probability of 55%(41-74). The median time of EFS was 30 months (15 - 70) with a 5-years probability of 46%(33-66). The cumulative incidence of relapse at 1 and 3 years was 17% (11-23) and 22% (15-29) respectively. The cumulative incidence TRM at 1 and 3 years was 10% (5-15) and 27% (20-35) respectively. At the last follow-up, 17 patients died, 6 due to relapse and 11 due to TRM. We noticed a high severe infection rate (56%) and 4% of deaths related only to infection. The univariate analysis showed a positive trend of rituximab on OS and relapse, and a significant protective effect on aGVHD>=2 (p=0.02). The multivariate analysis studying age, interval diagnosis-allo-HSCT, ABO and sex matching, disease status at allo-HSCT, CD34+ number, and rituximab, showed a positive significant impact of this last factor (rituximab) on OS and EFS [HR=0.1 [0-0.6] p=0.02 & HR=0.1[0-0.4] p=0.035 respectively]. Conclusion: We showed interesting results in terms of OS, relapse and TRM in patients with advanced CLL after Fludarabine/TBI allo-HSCT. The introduction of rituximab allowed a better outcome especially a significant reduction of incidence and severity of acute GVHD. Nevertheless there was still a high incidence of cGVHD, already known following the Fludarabine/TBI conditioning, leading us to propose either to increase the number of rituximab injections after allo-HSCT, or to test Fludarabine/busilvex/ATG associated to rituximab. Disclosures: No relevant conflicts of interest to declare.

SU-FF-T-203: In Vivo Dosimetry Using Disposable MOSFET Dosimeters for Total Body Irradiation

2005 ◽  
Vol 32 (6Part9) ◽  
pp. 1996-1996 ◽  
Author(s):  
TM Briere ◽  
RC Tailor ◽  
NB Tolani ◽  
KL Prado ◽  
RG Lane ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
In Vivo Dosimetry ◽  
Total Body

Total Body Irradiation Causes Residual Bone Marrow Injury by Induction of Persistent Oxidative Stress in Murine Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3209-3209
Author(s):  
Yong Wang ◽  
Lingbo Liu ◽  
Senthil Kumar Pazhanisamy ◽  
Aimin Meng ◽  
Daohong Zhou
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Total Body Irradiation ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Tissue Injury ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
Total Body

Abstract Abstract 3209 Poster Board III-146 Ionizing radiation (IR) and/or chemotherapy cause not only acute tissue injury but also have late effects including long-term bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to induction of hematopoietic stem cell (HSC) senescence. However, neither the molecular mechanisms by which IR and/or chemotherapy induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury, which were investigated in the present study using a total body irradiation (TBI) mouse model. The results showed that exposure of mice to 6.5 Gy TBI induced a persistent increase in reactive oxygen species (ROS) production in HSCs only for up to 8 weeks, primarily via up-regulation of NADPH oxidase 4 (NOX4). This finding provides the foremost direct evidence demonstrating that in vivo exposure to IR causes persistent oxidative stress selectively in a specific population of BM hematopoietic cells (HSCs). The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double strand breaks, inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetyl-cysteine (NAC) after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. These findings suggest that selective induction of chronic oxidative stress in HSCs by TBI leads to induction of HSC senescence and residual BM injury and that antioxidant therapy may be used as an effective strategy to mitigate IR- and chemotherapy-induced residual BM injury. Disclosures No relevant conflicts of interest to declare.

Benefits of online in vivo dosimetry for single-fraction total body irradiation

2014 ◽  
Vol 39 (4) ◽  
pp. 354-359 ◽  
Author(s):  
David J. Eaton ◽  
Alison J. Warry ◽  
Rachel E. Trimble ◽  
Maria J. Vilarino-Varela ◽  
Christopher H. Collis
Keyword(s):  
Total Body Irradiation ◽  
In Vivo Dosimetry ◽  
Single Fraction ◽  
Total Body

scholarly journals Patient dose analysis in total body irradiation through in vivo dosimetry

2012 ◽  
Vol 37 (4) ◽  
pp. 214 ◽  
Author(s):  
K Ganapathy ◽  
P. G. G. Kurup ◽  
V Murali ◽  
M Muthukumaran ◽  
N Bhuvaneshwari ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Patient Dose ◽  
In Vivo Dosimetry ◽  
Total Body

Identification of Novel Mutations In Ribosomal Genes In Patients with Diamond Blackfan Anemia (DBA) In Germany and Genotype-Phenotype Correlation Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2244-2244
Author(s):  
Mihaela Pali ◽  
Jessica Moetter ◽  
Joerg Meerpohl ◽  
Mutlu Kartal ◽  
Alexandra Fischer ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Growth Retardation ◽  
Ribosomal Proteins ◽  
Conflicts Of Interest ◽  
Ribosomal Genes ◽  
Treatment Modalities ◽  
Hematopoietic Stem ◽  
Organ Systems ◽  
Number Of Patients

Abstract Abstract 2244 In the current study, 122 index patients in addition to parents with DBA registered in the observational DBA study were screened for mutations in the aforementioned 11 genes. Overall, we detected mutations in 51% (n=62) of index patients in the following genes: RPS19 (33.6%, n=41), RPL5 (10.7%, n=13), RPL11 (3.3%, n=4), RPS26 (1.6%, n=2), RPS24 (0.8%, n=1) and RPS10 (0.8%, n=1). Only mutations altering the amino acid composition or resulting in splice site disruption (+/−1bp intronic) were included. Putatively pathogenic mutations localized in the 5‘UTR or intronic regions, (although not present as SNPs in healthy controls) were excluded from this study. In a high number of patients multiple genes were sequenced but no mutual mutations were found. RPS26 mutations detected in two patients included c.1A>G (previously reported by Doherty et al, 2010) and a novel initiation codon mutation, c.3+1G>A. Mutations detected in RPS10 and RPS24 were not previously described: c.71A>G (p.Lys24Arg) and c.2T>G. Various physical abnormalities were present in 57%, 75%, and 100% of patients with RPS19, RPL5/11, RPS26 mutations, respectively. Interestingly, no malformations were exhibited by probands with affected RPS10 and RPS24 genes. It is well known, that imbalances of ribosomal proteins can activate the p53 pathway: RPL5 and RPL11 (in addition to RPL23, RPL26, RPS3, RPS7) were reported to inhibit the activity of MDM2 thus influencing p53 activation. To assess if mutations in RPL5 and RPL11 might have different impact on physical development than RPS19, we compared the frequency of congenital abnormalities in both groups. The following organ systems were affected in patients with mutated RPL5/11 and RPS19 genes and physical anomalies, respectively: craniofacial region: 83% and 50% thumb: 33% and 12%, kidney 17% and 4%, heart: 67% and 46%, skeletal system: 17% and 25%, neurobehavioral deficits: 33% and 12%, skin pigment changes: 17% and 8%. Cleft palate was exclusive to RPL5/11 patients (p= .007; Fisher's exact test), and growth retardation was present in 60% of RPL5 vs. 8% of RPS19 patients (p= 0.008). While none of the patients with growth retardation and RPS19 mutation were small for gestational age (SGA), all but one RPL5 patients proved to be SGA. We next focused our analysis on hematological presentation and treatment modalities of these two subgroups. There were no differences regarding lowest and median platelet, white blood and absolute neutrophil count. Further evaluation of treatment outcome did not reveal any statistical asymmetry with regard to spontaneous remission, steroid or transfusion dependency and hematopoietic stem cell transplantation. In summary, we detected 62 distinct mutations in 6 ribosomal genes in 51% of German DBA patients. Growth retardation predominates in RPL5 patients and cleft palate is solely present in patients with RPL5 and RPL11 mutations. Mutated RPL5/11 vs. RPS19 genes do not seem to have a divergent influence on hematopoiesis in vivo. ***On behalf of the German DBA registry. Disclosures: No relevant conflicts of interest to declare.

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