Involved-Field Irradiation in Combination with Total-Body Irradiation (TBI) Does Not Increase Short-Term Toxicity Compared to TBI Alone in Patients with Advanced-Stage Low-Grade Non-Hodgkin Lymphoma

PURPOSE: High-dose therapy (HDT) is currently under investigation for patients with advanced low-grade non-Hodgkin lymphoma (NHL). We report on the toxicity of a modified HDT that combines total-body irradiation (TBI) with involved-field irradiation (IF-RT) for patients with bulky disease or residual lymphomas > 2 cm after induction chemotherapy. PATIENTS AND METHODS: 41 patients received HDT which consisted of high-dose cyclophosphamide and fractionated TBI (6 x 2 Gy) followed by autologous stem cell transplantation. Eleven patients received IF-RT prior to TBI, three patients had already received another radiotherapy treatment prior to HDT. RESULTS: After a medium follow-up of 19 months we observed an overall survival rate of 100%, and a relapse-free survival rate of 78%. Severe toxicity was observed only in one patient who developed a myelodysplastic syndrome, and another patient who showed signs of pneumonitis. About two thirds of the patients claimed minor toxicity of grade I-II according the LENT-SOMA scale, predominantly as a decrease in concentration, reduced sexual functioning, and musculo-skeletal pain. Correspondingly, laboratory tests showed grade I-II changes of blood counts, liver enzymes, hormone levels, and lung function. There was no excess toxicity in the patients who received IF-RT additional to TBI. CONCLUSIONS: HDT including TBI and prior IF-RT is feasible without excess morbidity. Careful follow-up is required to detect myelodysplastic syndrome or endocrine changes of ovarian or testicular function.     

专职化院前急救对重型颅脑损伤患者预后的影响

目的探讨专职化院前急救对重型颅脑损伤患者的预后影响。方法回顾分析2003年1月～2006年12月51例重型颅脑损伤患者院前急救资料,29例行专职化院前急救患者为研究组,22例行非专职化院前急救患者为对照组,比较两组患者出车时间、到达现场时间及预后。结果研究组院内反应时间及到达现场时间分别为（2．28±0．37）分和（10．07±1．27）分,较对照组明显缩短（P〈0．05）;专职化院前急救预后良好率为58．62％,明显优于非专职化院前急救（P〈0．05）;重度伤残及死亡率（41．38％）低于非专职化院前急救（P〈0．05）。结论专职化院前急救可明显提高重型颅脑损伤患者生存率与生存质量,降低死亡率与伤残率,改善患者预后。     

Total-Body Irradiation—Role and Indications

BACKGROUND AND PURPOSE: Total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry. MATERIAL AND METHODS: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center. RESULTS: For autologous HSCT approximately 10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, approximately 80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, approximately 35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI. CONCLUSION: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished.     

Total-body irradiation with 25-MV photons in advanced non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Preliminary results and complications.

Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma were treated with total-body irradiation (TBI). One group was treated after chemotherapy failed, while the other group received TBI initially. TBI was ineffective against CLL after chemotherapy failed. All patients with lymphocytic lymphoma who initially responded to chemotherapy but later relapsed were helped by TBI, as were 88% of patients with previously untreated lymphocytic lymphomas.     

Total body irradiation in Essen--dosimetry and physical treatment planning

Since 1975, in Essen 109 patients received total body irradiation (TBI) prior to bone marrow transplantation. About 80 patients were treated by bilateral 5.7 MeV photon beams. Three new TBI techniques were developed providing precise, homogeneous, reliable and reasonable a. p./p. a. TBI for adults and children. Systematic TBI dosimetry and the beam-zone method enable for individual treatment planning.     

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

Between August 1985 and October 1987 we treated 35 patients with chronic myeloid leukaemia (CML) by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n = 31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n = 35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. The addition of TLI to the standard protocol did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. We conclude that the addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This benefit is not associated with significantly increased toxicity.     

Detection of single-strand breaks and base damage in DNA of blood cells from leukaemia patients receiving chemo- and radiotherapy.

Chemotherapy combined with total-body irradiation (TBI), a conditioning regimen for bone-marrow transplantation (BMT), causes lesions in the cellular DNA of the patients treated. To understand possible consequences of the DNA damage induced during such treatment, information is required about the nature of the damage, the level of induction and its persistence, and about the importance of the various lesions for cell-lethality and/or mutation induction. Recently, we developed a sensitive immunochemical method to quantify single-strand breaks (SSB) in the DNA of mammalian cells. In addition, a modification of the so-called alkaline elution technique was introduced which allows quantification of SSB together with base damage (SSB+BD). These methods have now been applied successfully to study the in vivo induction and repair of DNA damage in WBC of leukaemia patients who prior to BMT were treated with cyclophosphamide (CY) and received TBI. SSB and SSB+BD were determined after two treatments with CY (60 mg kg-1) followed by TBI (4.5-8.6Gy). The CY treatments gave rise to rather persistent SSB. In addition to these, radiation-induced SSB and SSB+BD could be detected shortly after TBI. However, 105 min after TBI, these SSB could be observed no longer, as a result of rapid repair.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

人脐血间充质干细胞移植促进大鼠颅脑创伤后神经功能的恢复

目的 将人脐带血(human umbilical cord blood,HUCB)间充质干细胞(mesenchymal stem cells,MSCs)注射到创伤性脑损伤(TBI)大鼠顶叶皮层及海马区,观察神经细胞标志物的表达和促进神经功能的恢复.方法 HUCB-MSCs用双苯酰亚胺(bis-benzimide)标记24 h,通过立体定向将细胞注射到损伤脑组织内.全部大鼠分为假损伤组、损伤组(TBI)、对照组(TBI+PBS)和治疗组(TBI+MSCs).用免疫组化和免疫荧光标记的方法检测移植细胞的存活、迁移和分化情况,用神经损伤严重程度评分(NSS)对神经功能恢复结果进行评价.结果 在接受移植的脑创伤大鼠局部有大量的MSCs存活,一些细胞分化为神经元或神经胶质细胞,并表达NSE和GFAP等神经细胞的标志物,治疗组的神经功能评分较其他组有明显的改善.结论 HUCB-MSCs可明显改善脑创伤后神经功能的恢复,并能很好替代骨髓MSCs而用于干细胞移植.     

Renal Dysfunction after Total-Body Irradiation

PURPOSE: A retrospective analysis was conducted on the outcome of total-body irradiation (TBI) followed by bone marrow transplantation (BMT) on leukemia patients. Also studied was the risk of renal dysfunction after TBI/BMT with or without the use of selective renal shielding blocks. PATIENTS AND METHODS: The cases of 109 leukemia patients who received TBI as a component of the conditioning regimen for their BMT were reviewed. They received 12 Gy of TBI in six fractions over 3 consecutive days. Doses to eyes and lungs were reduced to 7 Gy and 8 Gy, respectively, by customized organ shielding blocks. After March 1999, renal shielding blocks were used to constrain the renal dose to 10 Gy. The patients were followed for a median period of 16.6 months (range: 0.3-180.1 months). RESULTS: The 2-year and 5-year overall survival rates were 55.4% and 43.2%, respectively. Renal dysfunction-free rates were different between those with and without renal shielding blocks: 100% and 78.5%, respectively, at 2 years. Overall survivals were not significantly different among these patients: 60.4% and 52.9%, respectively, at 2 years in patients with and without renal shielding blocks (p = 0.53). CONCLUSION: The use of selective renal shielding blocks provided evidence for reducing radiation-induced renal toxicities without decreasing the overall survival rate.     

早期外固定术在重型颅脑创伤合并四肢骨折中的应用

目的 探讨早期(<48 h)骨折外固定术在重型颅脑创伤(GCS≤8)合并四肢骨折患者中的临床应用效果.方法 统计重型颅脑创伤合并四肢骨折年龄、性别、颅脑创伤情况、骨折部位分布及其他全身情况等差异均无统计学意义的患者,根据骨折的早期(＜48 h)治疗方法不同,将重型颅脑创伤患者分为两组.A组:早期骨折外固定组(40例);B组:早期骨牵引、石膏固定等保守治疗组(57例).对比分析两组患者褥疮、肺炎、下肢静脉血栓形成等并发症发生情况,ICU时间、住院时间、骨折愈合时间、病死率等指标.结果 A组在感染率、褥疮、肺炎、下肢静脉血栓发生率方面明显低于B组(P＜0.05).A组的ICU时间、住院时间、骨折愈合时间短于B组(P＜0.05).A组的病死率低于B组,差异有统计学意义(P＜0.05).结论 针对重型颅脑创伤合并四肢骨折的患者,开展早期骨折外固定法与原有早期骨牵引、石膏固定等保守治疗方法相比,减少了并发症,缩短了恢复时间,降低了病死率.