LUNG DOSE DETERMINATION IN TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

Total body irradiation(TBI)combined with chemotherapy prior to bone marrow transplantation(BMT)is used successfully for treatment leukemias.It need a high and homogeneous radiation dose to all target cells,dispersed In the whole body.The lung is the most sensitive vital organ at risk in TBI.The lung dose must be within it's tolerable level.So,the determination of the lung dose is most Important for TBI.The determination of the lung dose is dependent on at least 8 parameters.In order to determine the effect of 8 parameters on the lung dose,using a system of phantom of Essen University hospital in F.R.Germany,a lot of measurements and a systematical investigation was made by varying 8 parameters,under the Essen translation TBI conditions.A analysis and discussion of results was made.

Study on Fractionated Total Body Irradiation before Hematopoietic Stem Cell Transplantation

OBJECTIVE To observe the dose and the complicationsfrom total body irradiation before hematopoietic stem celltransplantation.METHODS This study involved 312 patients with total bodyirradiation before hematopoietic stem cell transplantation. Theywere entered into the treated research from May 1999 to October2005. All patients had received the irradiation from ^(60)Co of anabsorbed dose rate of (5.2 ± 1.13) cGy/min. The total dose of TBIwas 7～12 Gy, 1 f/d × 2 d. A high-dose rate group (≥10 Gy) included139 cases and a low-dose rate group (< 10 Gy) included 173 cases.RESULTS The probability of acute gastrointestinal reactionsin the high-dose rate group was more compared with that in thelow-dose rate group. The differences for other reactions, such ashematopoietic reconstitution and graft survival rate, between thetwo groups were insignificant.CONCLUSION Using fractional total body irradiation at a doserate of 5 cGy/min, with a total dose of 7～12 Gy, 1 f/d × 2 d , withthe lung receiving under 7.5 Gy is a safe and effective pretreatmentfor hematopoietic stem cell transplantation.

Low Dose Total Body Irradiation (600 cGy) as a Conditioning Regimen in Allogenic Hematopoietic Stem Cell Transplant in Children with Acute Lymphoblastic Leukemia

Total body irradiation (TBI) is conditioning regimen in children with acute lymphoblastic leukemia (ALL) with a very high risk of relapse or in those who have not achieved remission and have relapsed and subsequently received allogenic hematopoietic stem cell transplantation (HSCT). A retrospective evaluation of 33 ALL patients in full remission with an indication of HSCT was performed to evaluate overall survival (OS) and event-free survival (EFS). The inclusion criteria included a myeloablative conditioning regimen of TBI at a dose of 600 cGy. The observed OS at 5 years was 50%, and the EFS of 32% we observed difference in the EFS stem cell origin;the peripheral blood (PB) 60%, and the umbilical cord blood (UC) accounted for 40%. Overall, 45% had a documented chimerism. The OS at 5 years from patients with chimeras was 75%, while those without chimeras had an OS at 5 years of 25%. The mortality in the first 100 days was 24%. A total of 24.2% of children presented with acute graft versus-host disease (GVHD), while 33% had chronic GVHD. Currently, there is no general agreement among all international centers regarding the optimum TBI dose. Our study reports an acceptable range of adverse events with a relatively low dose of 600 cGy.

Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation： a potential immunological mechanism

Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells （CB-MSCs） could improve the survival of mice exposed to lethal dosage total body irradiation （TBI）,and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4＋CD25＋Foxp3＋ regulatory T cell （Treg） percentage; CXCR3,CCR5,and CCR7 expressions on CD3＋T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage （CFU-GM） assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells （P＜0.05）,as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

Enhancement of antitumor immunity by low-dose total body irradiation is associated with selectively decreasing the proportion and number of T regulatory cells

Low-dose total body irradiation （LTBI） is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4^＋CD25^＋Foxp3^＋ regulatory T cells are markedly decreased in naive mice following treatment with LTBI. On the contrary, the CD4^＋CD44^＋/CD8^＋CD44^＋ effector-memory T cells are greatly increased. Importantly, naive mice treated with dendritic cell-gp100 tumor vaccines under LTBI induced an enhancement of antigen-specific proliferation and cytotoxicity as well as interferon-γ, （IFN-γ） secretion against FIO melanoma tumor challenge, compared to treatment with either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a reduced tumor burden and prolonged mouse survival. Our data demonstrate that LTBI＇s enhancement of antitumor immunity was mainly associated with selectively decreasing the proportion and number of T regulatory cells, implying the potential application of the combination of LTBI and a tumor vaccine in antitumor therapy.

Bivariate whole-genome linkage scan for bone geometry and total body fat mass

To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.

A SIMPLIFIED IN VIVO DOSIMETRY FOR TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

For TBI (total body irradiation) prior to BMT(bone marrow transplantation )and in order to guarantee exact treatment,it is necessary to perfect in vivo dosimetry to detect any deviation of the treatment and to verify the dose dis-tribution. A simplified and convenient transmission type in vivo dosimetry and problems are introduced and discussed.

Setting up the Model of Xeno-graft Verse Host Disease

Objective: To observe human to mouse one way mixed lymphocyte(MLC); And to set up the xeno-grats verse host disease Xeno-graft host disease(XGVHD) model,probing its immunologic mechamism.Methods: Mouse splenic lymphocyte were collected in asepsis and treated by mitomycin as activating cell. Human Peripheral blood lymphocytes (hPBL)were separated and gathered as reacting cell; Mouse splenic lymphocyte and hPBL were mixed to incubate for a week. Destroying recipient (mouse) immune system by total body irradiation (TBI) and intraperitoneal injecting CTX、MTX; Separating and collecting hPBL; Injecting hPBL to mouse by caudal vein. Results; ①HPBL in the experiment groups(mixed mouse lymphocyte) proliferated obviously, the amount of 3H-TdR in corporation increased evidently(P<0.05); The mean percentage of CD 4、CD 8、IgG 、IgM positive cells rose markedly. ②Experiment groups,the hPBL were found in the spleen and kidney tissue, fas protein expressing, we occasionally discovered and apoptosis cells.Conclusion: The human to mouse one-way MLC has obvious lymphocyte proliferation. By these means,we succeed in inducing XGVHD and setting up a XGVHD model.

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

Background:Gastrointestinal(GI)injury is one of the most common side effects of radiotherapy.However,there is no ideal therapy method except for symptomatic treatment in the clinic.Xuebijing(XBJ)is a traditional Chinese medicine,used to treat sepsis by injection.In this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were explored.Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E.The expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by immunohistochemistry.The expression of cytokines in the intestinal crypt was detected by RT-PCR.DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence.Results:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the intestine.Elevation of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after irradiation.The expression of Bax and p53 were decreased after XBJ treatment.Conclusions:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

Computational and Experimental Approaches for Evaluating Dose under a Block in TBI Geometry

Total Body Irradiation (TBI) patients are often treated at extended distances of several meters, with blocking made from high-Z materials placed close to the patients’ skin. Evaluating the dose under a block (e.g., for implanted medical device shielding purposes) in such a geometry is challenging. We compare the performance of two commonly used dose calculation algorithms, Anisotropic Analytical Algorithm (AAA) and Acuros XB, with Optically Stimulated Lumine- scence (OSLD) and ion chamber measurements in phantoms. The calculations and phantom measurements are also compared with in-vivo OSLD measure- ments. We find that OSLD and ion chamber measurements in phantom are good predictors of in-vivo measurements, while both AAA and Acuros XB sys- tematically overestimate the block transmission. We found Acuros XB to be accurate enough for a rough upper estimate (dose under block overestimated by 7% - 22%), while for AAA the overestimate was more severe (90% - 110%);the reason is that AAA does not account for the increase in pair production cro- ss-section in high-Z materials.

TBI Technique Improvements for Anesthetized Pediatric Patients Based on Near-Miss Incident Reporting

Purpose: To share our clinical experience of an optimized and comprehensive pediatric TBI technique. Methods and Materials: Through the use of incident learning, safety-critical areas were identified in our procedure for total body irradiation (TBI) for pediatric patients under anesthesia for bone-marrow transplant. The previous procedure lacked flexibility to accommodate various requests from the anesthesia team due to the wide range of patient sizes. To address this issue and to improve the process overall, we updated our procedure for TBI simulation, dosimetry planning, patient setup during treatment, and in vivo dosimetry. A simulation form was redesigned with additional detailed instructions and documentation requirements. The dose calculation procedure was reformulated to remove dependence on setup variations. Tissue compensation determination and therefore dose uniformity were improved by introducing rigorous calculation methods. Calculations were performed on 28 previously-treated patients to compare the dose uniformity using the new versus previous methods. Results: The new procedures improve interdepartmental communication, simplify the workflow, decrease the risk of treating patients in a setup that differs from that used during the simulation, and reduce dose heterogeneity. The new compensator design significantly improved patient dose uniformity: 0.8% ± 0.4% (new method) vs. 4.2% ± 2.3% (previous method) (p Conclusion: A near-miss incident reporting system was used to improve the safety and quality of pediatric TBI procedures under anesthesia.