造血干细胞移植前全身照射急性放射性反应与照射剂量的关系

目的探讨造血干细胞移植前全身照射急性放射性反应与照射不同总剂量及分次剂量的关系。方法回顾性分析2015年5月至2019年12月于石家庄平安医院造血干细胞移植前接受6 MV X线全身照射预处理的48例患者的临床资料。将患者按照射总剂量分为8 Gy组(12例)、10 Gy组(31例)和12 Gy组(5例),按分次照射剂量分为4 Gy/次组(17例)和5 Gy/次组(31例),总结比较各组患者放疗后的口腔黏膜、咽部、涎腺、上消化道、下消化道及肺的急性放射性反应发生情况。结果照射总剂量8 Gy组咽部急性放射性反应0级11例(91.7%),1级1例(8.3%);10 Gy组0级10例(32.3%),1级13例(41.9%),2级4例(12.9%),3级3例(9.7%),4级1例(3.2%);12 Gy组0级2例(40.0%),1级、2级、3级各1例(20.0%);照射总剂量8 Gy组咽部急性放射性反应较10 Gy组和12 Gy组轻,差异有统计学意义(χ2=11.338,P=0.003);其他部位急性放射性反应发生率差异均无统计学意义(均P>0.05)。分次照射剂量4 Gy/次组咽部急性放射性反应0级13例(76.5%),1级2例(11.8%),2级、3级各1例(5.9%);5 Gy/次组0级10例(32.3%),1级13例(41.9%),2级4例(12.9%),3级3例(9.7%),4级1例(3.2%);分次照射剂量4 Gy/次组咽部急性放射性反应较5 Gy/次组轻,差异有统计学意义(Z=-2.606,P=0.009);其他部位急性放射性反应发生率差异均无统计学意义(均P>0.05)。结论造血干细胞移植前全身照射总剂量8 Gy及分次剂量4 Gy/次能减轻咽部急性放射性反应。     

优化全身照射技术对造血干细胞移植后发生间质性肺炎影响的初步观察

目的:探讨优化医用直线加速器高能X线全身照射(total body irradiation, TBI)的技术对造血干细胞移植后发生间质性肺炎(IP)的影响.方法:28例患者接受以环磷酰胺(CY) 全身放疗±依托泊苷(Vp-16)为预处理方案的造血干细胞移植,TBI采用分割放疗、肺挡铅技术,其中19例患者采用热释光剂量片(TLD)监测全身放疗的肺吸收剂量,TBI总量12Gy,共6次,肺部剂量8.5Gy.结果:28例患者随访24～104个月,中位随访时间75个月,5年总生存率(OS)为(53.6±9.4)%,5年无复发生存(RFS)(71.1±8.6)%;19例接受热释光剂量片监测吸收剂量的患者,肺吸收中位剂量8.44Gy,脐部吸收中住剂量11.87Gy,全身剂量的不均匀性<±10%;28例患者无1例发生IP.结论:采用分割全身放疗、肺挡铅、并用热释光剂量片监测肺吸收剂量可降低IP的发生.     

白血病患者造血干细胞移植前单次全身照射的预后分析

目的 回顾性分析单次全身照射(SFTBI)后行造血干细胞移植的白血病患者的预后及相关因素.方法 2008 年9月前7年半余共102例患者行SFrBI后移植.比较不同病理类型、移植方式及不同TBI参数组间生存率、复发率及间质性肺炎(IP)发生率差异,分析生存率、复发率和IP发生率的相关因素.结果 随访15～1482 d(中位值406 d).随访率为95.1%,随访满1、3年者分别为86、55例.1、3年生存率分别为59.0%、44.0%,单因素分析3年生存率有差异因素包括移植前有无复发(20%:55%,χ2=6.33,P=0.012)、移植方式(异基因比自体基因移植,39%:68%,χ2=8.06,P=0.005)、急性移植物抗宿主病(aGVHD)级别(≥3级比0～2级,0%:54%,χ2=7.52,P=0.006)、移植后有无复发(19%:58%,χ2=10.13,P=0.001)、有无IP(23%:58%,χ2=8.35,P=0.004).Cox模型多因素分析对生存有影响因素只有≥3级aGVHD(χ2=12.74,P=0.000).1、3年复发率分别为30.0%、50.0%,移植前已有过复发比无复发的复发率明显升高(47%:16%,χ2=7.32,P=0.007),Cox模型多因素分析显示移植前已有过复发对术后复发有影响(χ2=9.39,P=0.020).IP发生率为35.0%,全身剂量均匀度>3%和≤3%的分别为27%和4%(χ2=5.21,P=0.023),急性腮腺炎有和无的分别为34%和3%(χ2=14.15,P=0.000),异基因移植和自体移植的分别为31%和8%(χ2=7.70,P=0.006).Logistic多因素分析显示移植方式、急性腮腺炎及全身剂量均匀度对IP发生有影响(χ2=10.08、10.08、7.69,P=0.002、0.002、0.010).结论 ≥3级aGVHD患者3年生存率明显下降,全身剂量均匀性对IP发生有重要意义,异基因移植者更易发生IP,急性腮腺炎与IP明显相关,可能对预测IP发生有一定价值.     

含全身照射方案的造血干细胞移植对难治性白血病的疗效

目的探讨含全身照射(TBI)预处理方案的造血干细胞移植(allo-HSCT)对难治性白血病的疗效和安全性。方法采用含TBI预处理方案的allo-HSCT治疗20例难治性白血病患者,采用骨髓加外周血干细胞联合移植,预处理方案包括阿糖胞苷、氟达拉滨及TBI等,全身照射采用6MV-X照射,移植物抗宿主病(GVHD)预防采用经典环孢菌素A(CSA)和氨甲蝶呤(MTX)及抗胸腺细胞免疫球蛋白(ATG)、CD25单克隆抗体,移植后观察并发症和患者无病生存等情况。结果 20例患者均获造血重建,植入证据检测证实100%为完全供者造血。TBI后患者有轻度恶心、呕吐、腮腺肿胀等症状,无1例发生间质性肺炎。中位随访时间为12.5个月(6～36个月),共8例发生GVHD,死亡2例;因感染死亡2例、复发死亡6例,其余10例患者仍无病生存,2年无病生存率为50%。结论含全身照射方案的造血干细胞移植,对难治性白血病是1种安全有效的治疗方案,可作为挽救治疗的关键技术。广泛应用于临床。     

全身照射(TBI)在骨髓移植中的应用

1987～1990年对40例白血病患者进行骨髓移植(BMT)时应用全身照射(TBI)。其中异基因骨髓移植(Allo-BMT)26例,自体骨髓移植(ABMT)14例。A110-BMT给予9.9Gy/3F及12Gy/3F,ABMT为10Gy/2F,放射源包括~(11)Co及电子直线加速器,照射剂量率为2～7cGy/Min,对ABMT肋骨补照4Gy,对CMYL(慢粒白血病)脾区照射10Gy/2F。经TBI后全部病人白细胞均降至零,以后逐渐恢复造血,粒细胞>0.5×10~2/L及血小板上升到50×10_8/L的时间在A110-BMT及ABMT组分别为29.9天、46.8天及26.6天及43.3天。 白细胞下降到零、脱发及咽痛、上腹不适三点是BMT极期的表现。     

450例全身照射患者的照射方法及结果分析

目的 探讨450例全身照射(TBI)患者的照射方法及结果.方法 (1)测算方法:①对TLD的剂量标定采用单点剂量标定法;②人体纵轴方向体中线吸收剂量的测算采用对皮肤表面入射与出射剂量的平均值并加修正的方法.(2)照射方法:①4个野照射方法:射线成水平入射,射野的对角线与患者人体长轴方向一致,患者取仰、侧卧位,组成两对平行对穿的照射野.照射方案采用患者在TBI前一周左右通过4个野等剂量预照射(预照剂量为TBI总量的1/10),筛选出均匀度最佳的仰、侧卧位相同或不同的剂量配比方案,用于TBI的正式照射.②小野照射方法:患者仰坐在特制木椅上,照射分左侧位和右侧位两野平行对穿照射.椅背可顺时针(CW)或反时针(CCW)旋转,脚蹬可前后移动并可固定.③双侧位照射方法:与4个野照射方法基本相同,但患者仅取仰卧位,射线分别从身体两侧入射形成一对平行对穿的照射野.在使用双侧位照射方法收治的患者中,有5例患者采用了FFBI治疗方案.另外,收治的全部TBI患者,在射线入射方向上,紧贴患者身体均放置一块具有一定建成厚度的有机玻璃散射屏.结果 ①使用4个野照射方法的87例患者,其人体纵轴方向体中线的不均匀度平均为±8.1%.②使用小野照射方法收治的91例患者,其不均匀度平均为±7.4%.⑧使用双侧位照射方法收治的272例患者,其不均匀度平均为±4.9%.结论 ①使用TLD或半导体剂量仪实时监测患者体表入射与出射剂量是TBI治疗重要的质量控制和保证.②对使用常规仰、侧卧位,射野不能完全包罗患者身体各个部位时,采用小野照射方法,它从过程到结果都优于4个野照射技术.③当射野的对角线＜110 em时,采用4个野和小野照射的均匀度都不及对角线＞180 cm患者取平卧的双侧位照射.④双侧位与前后野照射比较,各有特点.实际上后者更适合于使用PTBI治疗亭,患者取半坐立姿,分前后野接受多次TBI照射.⑤STBI虽不具有FTBI放射生物学的优势,但从某种意义上讲,它也是TBI的一种较为实用的形式.     

单次与分次全身照射对干细胞移植患者肾功能损伤及其影响因素分析

目的:探讨造血干细胞移植前全身单次和分次照射对移植患者肾功能的损伤及其影响因素。方法:回顾性分析2001-2010年我院以全身放射(TBI)为基础方案预处理后73例造血干细胞移植患者的临床资料。根据TBI方案不同,分为单次照射组(A组,8 Gy)、分次照射组(B组,12 Gy分6次照射)。根据血清肌酐水平分别评估肾小球滤过率(eGFR)的基线水平及TBI后1、4、12、18和24个月的eGFR变化,肾功能损伤定义为eGFR较基线水平下降≥30%,采用t检验及Kaplan-meier方法对病例随访资料进行肾存活生存曲线分析,比较两种TBI方式对肾功能的损伤。采用逐步逻辑回归方法分析年龄、TBI剂量率、环孢素以及移植物抗宿主病(GvHD)等因素对肾功能损伤的影响。结果:TBI后1和4个月时A组肾损伤的发生率分别为12.20%和34.15%,B组分别为9.37%和21.88%;且肾损伤程度〔(各观察时间点eGFR-基线水平eGFR)/基线水平eGFR〕A组大于B组,4个月时A组为-0.25±0.20,B组-0.14±0.18,差异有统计学意义,P<0.05。12、18和24个月时A组慢性肾损伤的发生率分别为34.15%、48.78%和48.78%,B组分别为28.13%、43.75%和46.88%,A组肾损伤的发生率高于B组,但两组患者各时间点的肾损伤程度差异无统计学意义,P>0.05。Kaplan-meier肾存活生存曲线显示,两组的肾存活函数均趋于下降,但B组肾存活率高于A组。逐步逻辑回归模型分析显示,干细胞移植后肾功能的损伤与年龄密切相关,而与照射剂量、环孢素应用及GvHD无关。结论:单次及分次全身照射均能够造成造血干细胞移植患者的急、慢性肾损伤,但单次照射的早期肾损伤较为明显,分次照射对肾功能的远期影响更小。年龄与干细胞移植患者的肾损伤密切相关。     

造血干细胞移植前全身照射的毒副反应及影响因素分析

目的　观察和分析造血干细胞移植前采用全身照射治疗所产生的近期和晚期毒副反应。方法　自１９９９年５月至２００５年１２月,我科对３１２例造血干细胞移植患者进行了全身照射。采用６０Ｃｏγ射线照射,患者取侧卧体位,腹脐处中心平面剂量率控制在４～６ｃＧｙ／ｍｉｎ,平均（５.２±１.１３）ｃＧｙ／ｍｉｎ,总剂量７～１２Ｇｙ,分１～３次照射,每天照射１次,照射期间制作个体化的肺挡铅进行肺屏蔽。结果　在全身照射后,患者近期出现了Ⅰ ～Ⅱ级的发热、胃肠道反应、口腔炎及出血性膀胱炎,均可耐受,无需特殊处理。间质性肺炎发生率为９.９％,造血系统重建和干细胞植活率达７０％以上,患者均未出现严重的肾功能衰竭。结论　采用剂量率５ｃＧｙ／ｍｉｎ照射,总照射剂量控制在７～１２Ｇｙ,肺中位剂量不超过７.５Ｇｙ,１次／天,共照射１～３次的剂量分割模式,是有效和安全的造血干细胞移植预处理方案。     

改进全身照射的新途径

作为骨髓移植预处理方案的重要组成部分,全身照射(TBI)的目的是消灭肿瘤,有效地抑制免疫反应,非造血系统毒性是其剂量限制毒性。如能进一步提高TBI的杀瘤作用和免疫抑制作用同时降低其毒性,将进一步提高TBI的疗效。已知照射剂量、剂量率、分割方式和体内剂量分布是TBI疗效的影响因素。 已有的动物和临床资料显示杀瘤作用、免疫抑制作用及治疗毒性均与TBI的剂量有明显的正相关关系。小量提高剂量就可明显地增强杀瘤和免疫抑制作用,但是非造血系统毒性也     

剂量分割模式照射人肺腺癌移植瘤后基因表达谱差异的初步研究

目的 研究总相同照射剂量、不同剂量分割方案对BALB/c-nu裸鼠移植瘤(人肺腺癌细胞系Anip973)基因表达的差异.方法 将移植瘤种鼠的肿瘤组织制备成肿瘤组织块,选择裸鼠右后肢外侧小腿腓肠肌处接种,建立移植瘤裸鼠模型.待肿瘤直径达1.0 cm时将48只裸鼠分成4个组:未照射空白对照组、2 Gy30次常规照射组(2 Gy组)、6 Gy10次大分割组(6 Gy组)、10 Gy6次大分割组(10 Gy组).大分割组均在2周内完成,所有照射完成后继续观察裸鼠1个半月.采用基因谱芯片技术检测4个组移植瘤细胞的基因表达差异,并进行实时PCR验证.结果 6、10 Gy组较2 Gy组上调了抑制细胞增殖和诱导凋亡的基因如Bax和BCL2L10,下调了促进细胞增殖基因如c-myc和EGF、抗凋亡基因以及XRCCA、RAD21、RAD23B等DNA损伤修复基因.PCR证实6 Gy10次组c-myc基因表达丰度明显低于2 Gy30次组和10 Cy6次组,分别为2.9%、5.6%、4.8%(P=0.000;P=0.002);10 Gy6次组c-myc基因水平相对于2 Gy30次组也有下降(P=0.069).结论 两个大分割方案较常规分割方案对BALB/c-nu裸鼠移植瘤(人肺腺癌细胞系Xnip973)在基因水平上生长抑制显著,6 Gy10次分割方案较10 Gy6次分割方案有更强的生长抑制作用.     

Total body irradiation and pneumonitis risk: a review of outcomes

A review was undertaken of all patients treated at Royal Adelaide Hospital, South Australia with total body irradiation (TBI) for the purpose of assessing the incidence of interstitial pneumonitis (IP) and possible prognostic factors for its development. The aim was also to assess the impact of IP and other prognostic factors on long-term survival outcome following bone marrow transplantation. A total of 84 patients received TBI, with 12 Gy in six fractions delivered using two different instantaneous dose rates of 7.5 and 15 cGy min(-1). This series included 26 cases of acute lymphoblastic leukaemia, 26 of multiple myeloma and 15 of acute myelogenous leukaemia. On multivariate analysis, a higher dose rate was independently significant for an increased risk of IP.     

全身分次放射治疗血液恶性肿瘤的临床研究

目的:观察接受分次全身放射治疗的血液恶性肿瘤患者的早晚期毒性反应及预后.方法:对14例血液恶性肿瘤患者进行分次全身放射治疗,作为异基因骨髓移植的预处理.结果:14名患者均能顺利完成全身分割放射治疗,早期急性反应均能耐受.经过一年以上随访,1年生存率为57％(8/14),5年生存率为37％(3/8).结论:患者对分次全身放射治疗具有良好的耐受性,可以作为异基因骨髓移植的重要预处理手段在临床上广泛应用.     

Fractionated total body irradiation for metastatic neuroblastoma

Twelve patients over one year old with neuroblastoma (NBL) metastatic to bone and bone marrow entered a study of adjuvant low-dose, fractionated total body irradiation (TBI). Six children who achieved a “complete clinical response” following chemotherapy (cyclophosphamide and adriamycin) and surgical resection of the abdominal primary received TBI (10 rad/fraction to totals of 100–120 rad/10–12 fx/12–25 days). Two children received concurrent local irradiation for residual abdominal tumor. The intervals from cessation of chemotherapy to documented progression ranged from 2–16 months, not substantially different from patients receiving similar chemotherapy and surgery without TBI. Three additional children with progressive NBL received similar TBI (80–120 rad/8–12 fx) without objective response.     

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756–1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment. Eight patients died of recurrent leukemia, four of interstitial pneumonitis, two of infection, one of veno-occlusive disease of the liver and one of cardiac failure. The median survival time was 181 days.     

The combined modality therapy of diffuse histology non-Hodgkin's lymphoma with cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) and total body irradiation

The combination of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) alternating with total body irradiation (TBI) has been shown earlier to be effective therapy in patients with malignant lymphoma who have received prior chemotherapy and/or radiation therapy. A limited institutional pilot study was therefore done by the Southwest Oncology Group between October 1977, and November 1978 to test the benefit of this program in previously untreated persons with Stages 3 and 4 diffuse histology non-Hodgkin's lymphoma. Eleven evaluable patients with the following histologies were treated: 7 poorly differentiated, 2 with histiocytic, 1 with mixed lymphoma and 1 with well-differentiated morphology. CHOP was given in the following manner: cyclophosphamide 400 mg/M2 IV day 1, adriamycin 40 mg/M2 IV day 1, vincristine 2 mg IV day 1, and Prednisone 100 mg po daily X 5. Forty-five rad total body irradiation was delivered in three fractions on days 21, 23 and 25. Chemotherapy was repeated on day 42, etc., until four cycles of CHOP and three cycles TBI (135R) were delivered. Responses were seen in 8/11 patients (6 CR and 2 PR); 5 persons are currently alive and 6 are dead. Two of the living patients are alive with disease and the remainder are in unmaintained remission. Two persons died with no response and one died in complete remission of an unrelated illness. The median duration of remission is 15 months and the median survival for all patients is 48 months. The therapy was well tolerated with a mean nadir leukocyte count of 3,020 X 10(9)/microliters (range 1.2-5.5) and a mean nadir platelet count of 188 X 10(9)/microliters (range 016-270). As delivered, this program is capable of producing durable remissions and needs to be verified in a larger series of patients.     

Total body irradiation in chronic myeloid leukemia

Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following busulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.     

Study on fractionated total body irradiation before hematopoietic stem cell transplantation

OBJECTIVE To observe the dose and the complications from total body irradiation before hematopoietic stem cell transplantation. METHODS This study involved 312 patients with total body irradiation before hematopoietic stem cell transplantation. They were entered into the treated research from May 1999 to October 2005. All patients had received the irradiation from ^60Co of an absorbed dose rate of （5.2 ± 1.13） cGy/min. The total dose of TBI was 7-12 Gy, 1 f/d × 2 d. A high-dose rate group （〉 10 Gy） included 139 cases and a low-dose rate group （〈 10 Gy） included 173 cases. RESULTS The probability of acute gastrointestinal reactions in the high-dose rate group was more compared with that in the low-dose rate group. The differences for other reactions, such as hematopoietic reconstitution and graft survival rate, between the two groups were insignificant. CONCLUSION Using fractional total body irradiation at a dose rate of 5 cGy/min, with a total dose of 7-12 Gy, 1 f/d × 2 d, with the lung receiving under 7.5 Gy is a safe and effective pretreatment for hematopoietic stem cell transplantation.     

Total body irradiation in non-Hodgkin's lymphoma.

Between October 1972 and August 1977, low-dose fractionated total body irradiation (TBI), 150–300 rad, was selected for 48 patients with previously untreated non-Hodgkin's lymphoma staged II, III and IV. In 63% of the patients the disease had a nodular pattern; there were no patients with diffuse histiocytic lymphoma.All but 2 patients responded to TBI. The 4-year actuarial survival was 71% for the nodular group and 57% for the diffuse group.There were no acute symptoms during the course of treatment and no mortality associated with the treatment. Seventeen per cent of the patients developed transient platelet counts less than 30,000/mm³. Four required hospitalization for correction of thrombocytopenia and/or infection.The majority of patients who failed more than 3 months after initial complete remission were placed back in remission with either chemotherapy, TBI, or local irradiation. Patients with persistent disease after TBI showed a less favorable response with chemotherapy.A selected group of 15 patients in relapse after chemotherapy or localized radiotherapy were treated with TBI. Eleven responded to treatment, while 4 showed no useful response. The median survival for this group was slightly over 2 years. Twenty per cent developed transient platelet counts less than 30,000/mm³.     

Half body irradiation

Twenty-one patients with complaints of severe pain from disseminated breast cancer were treated with half body irradiation with a single dose of 600 to 800 rad. All of them had a relief of pain for periods ranging from 14 to 280 days, with a median duration of 101 days. The objective effects of a single radiation dose was studied in 15 patients with lung metastases. The growth delay observed in these patients was of the same order as the periods of pain relief observed in breast cancer patients after half body irradiation. In general a longer lasting palliation was obtained in patients with slowly growing tumors.