Total lymphoid irradiation and total body irradiation for allogeneic bone marrow transplantation in aplastic anemia

Between April 1980 and June 1989, 15 patients with severe aplastic anemia (SAA) were treated at Hyogo College of Medicine with bone marrow transplantation (BMT) after preparation consisting of cyclophosphamide (CY) and total lymphoid irradiation (TLI) or total body irradiation (TBI) for the purpose of reducing the incidence of graft rejection. All patients had initial evidence of engraftment after the first transplantation except for one patient who died of heart failure due to CY on the third day after transplantation and could not be evaluated for engraftment. Rejection later occurred in four of these 14 patients, who then underwent successful regrafting. One of these patients, who was conditioned with CY alone at the first grafting, underwent successful regrafting after a conditioning regimen of CY and TBI. In the other three patients, irradiation was performed twice as the conditioning regimen. Thus, 14 of 15 patients underwent successful BMT and are alive with restored hematopoietic function. From the above results, the combination of TLI or TBI and CY was considered to be very useful as a conditioning regimen for BMT in patients with SAA.     

Compromising Effect of Low Dose-rate Total Body Irradiation on Allogeneic Bone Marrow Engraftment

The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1^a → B6-Gpi-1^b], H-2 compatible allogeneic [BALB.B (H-2^b) → B6 (H-2^b)] and H-2 mismatched allogeneic [BALB/c (H-2^d) → B6 (H-2^b)]. TBI was delivered over a range of doses at either a high (HDR, 40 cGy/min) or low (LDR, 2 cGy/min) dose rate followed by infusion of 10⁷ bone marrow cells from syngeneic or allogeneic donors. The level of donor (Gpi-1^a) engraftment was determined from blood Gpi-typing at different times after TBI and BMT. Radiation dose–response relationships corresponding to long-term haemopoietic engraftment at 20 weeks showed a dose-sparing effect of LDR that became more prominent with increasing genetic disparity between donor and host. For fully allogeneic (H-2 incompatible) BMT, a dose as high as 16 Gy LDR was still not sufficient for achieving chimerism in all recipients. In many cases allogeneic BMT gave transient blood chimerism enabling the recipient to survive the acute effects of high dose TBI with full long-term repopulation from surviving stem cells of the host. Radiation cell survival curves were obtained for the frequency of alloreactive precursors of proliferating T-lymphocytes (pPTL) remaining in the spleen at 1 day after TBI. A radiation dose-sparing effect of LDR was also found for pPTL depletion. These data suggest that radiation damage repair during LDR irradiation in an immunocyte target cell population is mainly responsible for enhanced graft rejection thus rendering protracted TBI less effective for application in clinical allogeneic BMT.     

The effect of small radiation doses: desoxyribonucleic acid (DNA) synthesis and DNA repair by the thymus, spleen and bone marrow cells of rats following fractionated whole-body X-ray irradiation

After three to seven days following to fractionated total body X-ray irradiation (TBI) (four exposures with doses of 0.3 to 5.0 cGy per fraction at intervals of 24 hours), a maximum 50 percent stimulation of the semiconservative DNA synthesis (SDS) of spleen cells was measured in vitro. This was not dependent of the fact if an acute high-dose (400 and/or 800 cGy) unique irradiation was applied after the fractionated TBI at the moment of stimulation. A significant increase of 3H-thymidine incorporation into the DNA of bone marrow and thymus cells was only found when doses of 1.25 cGy per fraction had been used. After fractionated TBI with doses of greater than or equal to 5 cGy per fraction, an increase of DNA synthesis resistant to hydroxyurea ("unprogrammed" DNA synthesis, UDS) was demonstrated in spleen cells. The UV-stimulated UDS decreased proportionately. The sedimentation of thymus, spleen, and bone marrow nucleoids in a neutral saccharose gradient gave no evidence of an increased DNA repair capacity after fractionated TBI. Whereas the SDS stimulation by fractionated TBI with small doses can be explained by a modified proliferation behavior of exposed cells, the UDS behavior of spleen cells after considerably higher radiation doses suggests regenerative processes correlated with an increased number of cells resistant to hydroxyurea and cells presenting an UV repair deficiency. These findings can be considered to be a further proof of the assumed immune-stimulating effect of small radiation doses.     

Interstitial pneumonitis after allogeneic bone marrow transplantation following total body irradiation.

The records of 40 patients who received allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine under the same conditioning regimen using cyclophosphamide and total body irradiation (TBI) from January 1984 to August 1989 were analyzed. The dose rate of TBI was 10 cGy per minute, and the total dose was 10 Gy (2.5 Gy daily for 4 days). Interstitial pneumonitis (IP) occurred in 13 of 40 patients, and was fatal in five patients. The probability of developing IP during the first year was 31%. We performed univariate analysis on the following factors but did not find any significant risk factors for IP: age and sex of patient, sex mismatch, ABO mismatch, grade of acute graft-versus-host disease, post immunosuppression regimen, and number of marrow cells transfused.     

Immunosuppressive role of radiotherapy in bone marrow transplant in patients with aplastic anemia

From April 1976 through August 1989, 66 patients with aplastic anemia were treated on either of two immunosuppressive regimens in preparation for allogeneic bone marrow transplantation (BMT) from matched donor. Seventeen patients were treated with cyclophosphamide (50 mg/kg for 3 days) followed by thoracoabdominal irradiation (TAI), 6 Gy/1 fr and 2 patients, receiving marrow graft from partially matched family donors, were treated with cyclophosphamide (50 mg/kg for 3 days), TAI (6 Gy/1 fr) and Ara-C (4 g/mq for 2 days). Forty-seven more patients were treated with cyclophosphamide alone (50 mg/kg for 4 days). All patients received prophylactic treatment with methotrexate (15) or cyclosporine A (51) to avoid graft-versus-host disease. Mean time to engraftment was 12 days after chemotherapy and TAI and 15 days after cyclophosphamide (Cy) alone. No marrow rejections were observed in the TAI group: the two infants that received partially matched marrow allografted and are alive and well. Two patients treated with cyclophosphamide alone rejected allogeneic marrow. Long-term overall survivals are similar: 64% for TAI + Cy group and 56% for Cy alone group. In spite of the immunosuppressive regimen employed, young patients (under 20 years) do better than older ones (survival: 65% vs 45%, respectively). Thus, patient's age seems to be the main factor determining overall survival after allogeneic BMT. We conclude that the use of irradiation does not add significantly to the survival of aplastic patients; given the possible toxic long-term effects of irradiation, it would probably be wise to restrict the combined use of cyclophosphamide and irradiation to the patients sensitized to their donors, to those receiving partially matched marrow from family donors or in programs involving T-cell depletion.     

Whole body irradiation in conditioning for bone marrow transplantation. Experiences with 35 cases of leukemia

Total body irradiation, carried out in two different regimens (10 Gy single dose; 200 cGy X 5 fractions) has been used in 35 patients with acute leukaemia or chronic leukaemia in chronic or accelerated phase, in preparation for bone marrow transplantation. The dose rate was in the range of 2-4 cGy . min-1. No lung shielding was adopted. The role of total body irradiation in the development of interstitial pneumonitis is considered. Rather than to the regimen of total body irradiation--single dose or five fractions--the incidence of interstitial pneumonitis seems to be related to other factors; mainly to the presence of Graft-versus-Host-Disease: Five patients out of six with III or IV grade GvHD, developed interstitial pneumonitis; only one patient out of twenty without GvHD or with a low grade GvHD developed interstitial pneumonitis.     

153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies

This study examined the safety of adding 153Sm lexidronam to standard conditioning regimens in patients undergoing stem cell transplantation for marrow based haematological malignancies in whom total-body irradiation as part of conditioning was desirable but not feasible. Ten such patients were enrolled, seven with multiple myeloma. An escalating regimen of 19-45 GBq of 153Sm lexidronam was added 12-14 days prior to the standard transplantation regimen. Evaluation parameters included time to engraftment, status at day +100 by International Bone Marrow Transplant Registry (IBMTR) criteria and toxicity during this period. Absorbed marrow radiation doses were estimated using the MIRDOSE 3 program. No adverse events were attributable to 153Sm lexidronam. Of the seven patients with multiple myeloma, four achieved complete response, two partial response, and another had stable monoclonal band at 3 months post-transplant. One patient with Refractory Anaemic with Excess Blasts in transformation (RAEBt) died of a presumed fungal infection, whilst another with acute myeloid leukaemia relapsed, dying at day +153. A patient with low-grade lymphoma showed no evidence of residual disease at day +100. The total marrow absorbed dose was estimated to be 0.7+/-0.2 mGy x MBq(-1). Regional uptake was markedly non-uniform with poor uptake in the appendicular skeleton. Dose-limiting toxicity was not attained. At the activities used 153Sm lexidronam was not associated with additional toxicity in this population. Adequate absorbed radiation dose to appendicular marrow is unlikely to be deliverable by this approach alone.     

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (188Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2+/-2.1 (range 6.9-15.8) GBq 188Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4+/-5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.     

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates (¹⁸⁸Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2DŽ.1 (range 6.9-15.8) GBq ¹⁸⁸Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4LJ.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking ¹⁸⁸Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia.     

Contrasting Dose-rate Effects of γ-irradiation on Rat Salivary Gland Function

The aim of this study was to investigate the effects of ⁶⁰Co irradiation delivered at high (HDR) and low (LDR) dose-rates on rat salivary gland function. Total-body irradiation (TBI; total doses 7·5, 10 and 12·5 Gy) was applied from a ⁶⁰Co source at dose-rates of 1 cGy/min (LDR) and 40 cGy/min (HDR) followed by syngeneic bone marrow rescue. Four days before and 1–30 days after TBI, submandibular and parotid saliva samples were collected in male albino Wistar rats using Lashley cups. Lag phase and flow rate were recorded, and [Na⁺] and [K⁺] were measured. The severity of salivary gland dysfunction for each dose-rate was dependent on total TBI dose in all parameters. LDR irradiation significantly enhanced the increase of lag phase, while it tended to further decrease flow rate during days 0–3. At later times the reverse effect was seen with significant LDR sparing in most cases. The changes in [Na⁺] and [K⁺] showed similar trends; LDR had an enhancing effect for early damage, while beyond day 3 it consistently produced less damage. From this dose-rate study it is concluded that the early postirradiation changes in salivary gland function are probably predominantly caused by irradiation damage to membrane structures and are less the result of reproductive failure. The later changes in salivary gland function are probably mainly dependent on repopulation of surviving stem cells.     

Radiation dose as a factor in host preparation for bone marrow transplantation across different genetic barriers.

Engraftment of donor bone marrow in relation to total body irradiation (TBI) dose was studied in syngeneic (B6----B6), MHC-compatible (BALB.B----B6) and MHC-incompatible allogeneic (BALB/c----B6) murine bone marrow transplantation (BMT) models. For each BMT combination radiation dose-response curves were obtained from stable long-term bone-marrow chimerism using Gpi-1 phenotyping and this was compared with the growth of exogenous CFU-S. Syngeneic engraftment required the lowest TBI doses limited to ablation of host haemopoietic stem cells. Resistance against H-2-compatible allogeneic engraftment was evident at low radiation doses (less than 5.5 Gy) but at 6 Gy and above the level of chimerism was comparable to syngeneic transplants, which indicated effective immunosuppression. Higher TBI doses were needed for engraftment as the immunological barrier was increased using fully H-2-incompatible allogeneic transplants. The high TBI dose (9.5 Gy) needed for suppression of spleen endocolonies in the CFU-S assay meant that rejection of exogenous bone marrow was evident only across the larger immunological barriers. When the fully allogeneic combination was reversed (B6----BALB/c) both CFU-S and chimerism data showed less rejection. The steep dose-response relationships show how engraftment is critically dependent on TBI dose, as well as the genetic disparity between donor and host.     

异基因骨髓移植的植入证明

本文对我院1987年12月至1989年11月间进行的9例HLA相合的异基因骨髓移植供受者的植入情况做了分析。我们采用了国际骨髓移植登记处的移植成功指标,及常规的细胞遗传学检查,结果全部患者均有间接的临床植入证据,其中5例有直接的细胞遗传学证据。本文综合文献提示,细胞遗传学分析在移植证明中具有很重要的意义,但其缺陷也是显而易见的。DNA-RFLP的检测可弥补常规方法的缺陷,并获得准确可靠的植入依据。     

Total body irradiation followed by bone marrow transplantation: comparison of once-daily and twice-daily fractionation regimens

Purpose The purpose of this study was to evaluate the results of two sequential total body irradiation (TBI) regimens, especially focusing on pulmonary complications. Materials and methods Patients with malignant disease who underwent TBI followed by bone marrow transplantation were retrospectively reviewed. There were 86 patients (51 males, 35 females). Altogether, 36 patients were treated on twice-daily fractions of 2 Gy for 3 days to a total 12 Gy (group A). Another 50 patients were treated on once-daily fractions of 2.4 or 3.0 Gy for 4 or 5 days to a total 12 Gy (group B). Results The 5-year overall survival rate was 49.2%, and relapse-free survival was 44.3%. There were no significant differences between the two groups regarding overall survival (P = 0.1237) or relapse-free survival (P = 0.1548). Two patients in group A had interstitial pneumonitis of grade 3 or higher severity compared with three patients in group B. There was no significant difference between patients in group A (5-year probability rate was 7.6%) and patients in group B (5-year probability rate was 13.9%) (P = 0.9519). Conclusion We concluded that our once-daily TBI regimen is feasible and had the benefit of reducing the complexity of TBI. We believe that further investigation of the TBI regimen is needed.     

Late Effects of Cyclophosphamide and Total Body Irradiation as a Conditioning Regimen for Bone Marrow Transplantation in Rats (a Preliminary Report)

Summary

The longterm survival and occurrence of neoplastic and nonneoplastic lesions following total body irradiation (TBI), 8·5 Gy, with or without additional cyclophosphamide (Cy; 100 mg kg^?1 i.p.) treatment as a conditioning regimen for bone marrow transplantation (BMT) were studied in male BN/BiRij rats.

The two groups of rats that were treated with Cy (Cy and Cy + TBI) that survived beyond 100 days after treatment, had a severely decreased median (post treatment) survival time (Cy + TBI: 14·5 months and Cy: 14·1 months). Survival time in the TBI group was moderately decreased (18·5 months) as compared with the untreated controls (27·2 months). All treatment modalities were carcinogenic according to the raw data. After Cy-treatment a high incidence of, frequently multiple, malignant nerve-sheath tumours (Cy: 66 per cent, Cy + TBI: 31 per cent, controls: 2 per cent) was observed.

TBI induced an increased occurrence of a great variety of tumours, especially mesenchymal tumours. This effect was more pronounced in animals receiving TBI alone as compared to animals receiving the combined treatment of Cy + TBI; an effect that most likely resulted from the longer median survival after TBI. The multi-target effect of TBI was also reflected in the occurrence of nonneoplastic effects in a variety of tissues, including high incidences of biliary cysts in the liver and severe testicular atrophy.

The most important Cy-induced nonneoplastic lesion was incisor dysplasia, which resulted in feeding problems that could only be partly overcome by administering powdered food. Early mortality in the Cy-treated groups was associated with emaciation and generalized organ atrophy.

A more definitive estimate of the late effects of supralethal chemoradiotherapy as part of a treatment of malignant disease has to await the results of various conditioning regimens for BMT in rats employing the acute BN myelocytic leukaemia (BNML) as a rat model for human acute myelocytic leukaemia (AML).     

医源性急性放射病的临床探讨

目的 通过观察医源性急性放射病的临床和治疗经验，为事故性放射病的救治提供依据。方法 观察41例经过大剂量照射预处理的自体外周血造血干细胞移植患者的外周血象、体温和症状，并作统计学比较与相关分析。结果 照射后患者外周血白细胞、血小板逐渐下降，平均于照后第10天、第13天至最低值，分别于第18天、第17天恢复，血红蛋白仅有轻至中度降低。移植后使用rhG-CSF与未使用rhG-CSF患者造血重建时间差异有统计学意义。移植前采集的单个核细胞数与骨髓重建时间呈负相关。照射副作用除常见呕吐、乏力、腮腺肿大、口腔溃疡、肝功异常及皮肤损伤外，25．6％患者照射后体温升高。粒细胞减少或缺乏期感染发生率为63．4％，多为轻度，心脏功能及肾脏功能基本不受影响。患者均能平稳渡过骨髓抑制期。结论 rhG-CSF的应用可明显缩短粒细胞缺乏期，促进骨髓重建；而移植前采集足够数量的单个核细胞是治疗医源性放射病、缩短造血恢复时间的关键；严格实行全环境保护和及时、联合、足量应用抗生素的原则为医源性急性放射病患者能够顺利渡过极期、减少感染等合并症提供了保证。     

口服携带人血小板第四因子的减毒沙门氏菌对放射损伤的保护作用

目的以减毒沙门氏菌SL3261为载体研究通过口服途径血小板第四因子(plateletfactor4PF4)对小鼠放射损伤的保护作用。方法将携带PF4基因的真核表达载体pIRES2EGFP转化减毒沙门氏菌SL3261,通过口服途经1×108个3d个菌株的剂量饲服小鼠,在第3次饲服后12h小鼠接受700cGy剂量60Co全身照射。以绿色荧光蛋白(greenfluorescenceproteinGFP)、外周血象及流式的检测、骨髓集落培养、小鼠生存期的观察研究PF4对造血系统的保护作用。结果照射后SL3261PF4治疗小鼠的肝脏、脾脏、肾脏、小肠、外周血及骨髓分别检测到绿色荧光蛋白的表达。照射后第7和14天SL3261PF4组小鼠骨髓细胞总数(marrowmononuclearcellsMNC)、粒巨集落细胞形成细胞(granulocytemacrophagecolonyformingunitCFU-GM)和高增殖潜能集落形成细胞(highproliferatingpotentialcolonyformingcellsHPP-CFC)数量与对照组有明显差异(P<0.05),生存期明显延长。结论本研究首次证实以减毒沙门氏菌SL3261为载体,口服PF4基因治疗可以保护小鼠免受放射损伤,并促进放射损伤后小鼠的造血恢复。     

一种侧卧位X射线分次全身照射技术及剂量监测结果分析

目的 报道一种侧卧位前后对穿X射线分次全身照射技术,并对照射中的实时剂量监测结果进行分析。方法 采用Varian Trilogy医用电子直线加速器10 MV X射线,行水平野对穿全身照射,源到模体表面距离390 cm,测量X射线全身照射条件下的射野百分深度剂量、离轴剂量分布及绝对剂量输出。对10例患者采用侧卧位前后对穿野分次全身照射。照射处方剂量1200 cGy/6次,共3 d,体中线剂量率约5.0 cGy/min。治疗时利用多通道半导体剂量计实时监测患者剂量准确性及剂量分布均匀性,采用固体水进行剂量非均匀性补偿。结果 治疗条件下模体测量射野离轴剂量分布均匀性<±5.0%,最大剂量点处绝对剂量输出为0.0721 cGy/MU。10例患者均能够顺利完成侧卧位治疗,各个部位监测总剂量偏离处方剂量-4.9%~6.7%,平均监测剂量均匀性<5.0%。结论 侧卧位X射线全身分次照射技术患者耐受性好,照射过程中实时监测剂量,采用固体水进行剂量非均匀性补偿,能够保证患者接受准确均匀的剂量分布,方法简便易行。     

Radiotherapy and High-Dose Chemotherapy in Advanced Ewing's Tumors

BACKGROUND: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (< 2 years after diagnosis) or multifocal relapse. PATIENTS AND METHOD: As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Düsseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) or Double-ME with whole lung irradiation up to 18 Gy (without TBI). RESULTS: The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy. CONCLUSION: High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion.     

全身淋巴结X线照射预处理在活体肾脏移植中的应用

目的探讨非清髓性全身淋巴结照射（TLI）预处理在活体供肾肾移植中应用的安全性和有效性。方法共5例受体接受了TLI,平均年龄27岁。供受体的HLA-A、B、DR6个抗原中4个抗原错配1例,3个抗原错配2例,1个抗原错配2例。供肾切取均采用手辅助腹腔镜活体供肾切取手术。TLI治疗从移植手术前5天开始,90cGy／d,共5天。术中和术后的免疫抑制药物方案与同时期的活体或尸体肾移植相同,但剂量略减少。术后定期检测受体外周静脉血白细胞绝对值;流式细胞仪检测T细胞、CD4^＋T细胞、CD8^＋T细胞和Th1、Th2亚群的变化;观察免疫抑制药物的使用情况、移植肾状态、急性排斥反应频率和相关副作用。结果受体外周血白细胞在术后的1～2周达最低值,12周观察期内均未恢复到移植术前水平。T细胞总数和CD4^＋T细胞、CD8^＋T细胞在术后的1～2周内达最低值,300天的观察期内未恢复到移植前水平;在TLI治疗后Th1细胞百分比减少,Th2细胞百分比略有增加,因此Th2细胞相对增多。观察期内未发生移植肾排斥反应,移植肾功能正常。免疫抑制剂使用量低于同时期的其他活体肾脏移植和尸体肾脏移植受体。没有任何感染等并发症发生。结论非清髓性TLI是一种安全有效的免疫抑制治疗手段,可以获得较长时间的免疫抑制状态,在减少肾脏移植排斥反应的基础上,减少了其他非特异性免疫抑制剂的应用,是一个理想的活体肾脏移植的预处理方案。     

Total body irradiation in the conditioning of autologous bone marrow transplants in acute leukemias and lymphomas

From january 1984 to may 1986, 31 patients, 15 ANLL, 8 ALL (in remission status) and 8 NHL (6 in remission, 2 in relapse) have been treated with chemo-radiotherapy [cyclophosphamide 60 mg/kg X 2 days + total body irradiation (TBI): 10 Gy/1 fr. in ANLL and NHL patients, 12 Gy/3 fr./3 days with 4 Gy boost testicular dose in ALL] and autologous bone marrow transplantation (BMT). Seventeen patients are alive, 16 in remission: 9 (60%) ANLL, 2 (25%) ALL, 5 (62%) NHL (median 8+ months, follow up 1+/29+); 2 patients presented interstitial pneumonitis (6.45%). In this series, very good results have been achieved in ANLL, where no relapse was noted, encouraging achievements in NHL, with 2/6 relapses; unsatisfactory results in ALL, with 4/8 relapse. Advantages and disadvantages of autologous relative to allogenic BMT, and of conditioning regimen with or without TBI are discussed.