Reteplase in the treatment of peripheral arterial and venous occlusions: a pilot study

PURPOSE: Reteplase, a truncated mutant of tissue plasminogen activator, has been used successfully in the treatment of acute coronary occlusion, but, heretofore, it has not been investigated in the setting of peripheral vascular occlusion. Reteplase is a potential recombinant thrombolytic agent that may offer an appropriate alternative to currently employed plasminogen activators. MATERIALS AND METHODS: Over a 6-month period reteplase was used to treat peripheral vascular occlusions at five centers in the United States. The agent was used in peripheral arterial occlusion (n = 26, 70.3%) or venous occlusion (n = 11, 29.7%), in doses ranging from 0.5 to 2.0 U/h, infused directly into the thrombus. A lacing dose (4.3 +/- 0.9 U) was employed in 17 patients (45.9%), and 25 patients (67.6%) received concurrent heparin therapy in a subtherapeutic dose (n = 14, 37.8%) or as full therapeutic anticoagulation (n = 11, 29.7%). RESULTS: The 26 patients with arterial occlusions received a total dose of reteplase that averaged 20.5 U +/- 5.3 (mean +/- SEM), ranging from 3.5 to 82 U. The duration of infusion was 19.3 hours +/- 2.4 with a range of 0.2-36 hours. Complete dissolution of the occluding thrombus was achieved in 23 patients (88.5%). Hemorrhagic complications developed in eight patients (30.8%) and were major in five patients (19.2%). No patient experienced intracranial bleeding. Although there was no association between the dose regimen and thrombolytic efficacy, bleeding complications appeared to be more frequent as the dose was increased from 0.5 to 2.0 U/h. The 11 patients treated for deep venous thrombi received an average of 32.6 U +/- 7.4 of reteplase, ranging from 6 to 75 U over a mean length of time of 31.1 hours +/- 7.3 (range, 4-84 hours). Complete dissolution of thrombus occurred in eight patients (72.7%). Hemorrhagic complications developed in three patients (27.3%) and one of the episodes was major (9.1%). No patient experienced intracranial hemorrhage. CONCLUSIONS: Reteplase appears to be an acceptable alternative thrombolytic agent with a satisfactory safety and efficacy profile in the setting of peripheral arterial and venous occlusion. As such, it may provide an attractive alternative for the treatment of peripheral arterial and venous thrombotic occlusions. However, definitive conclusions must await the results of controlled comparisons of reteplase to other thrombolytic agents.     

Reteplase monotherapy and reteplase/abciximab combination therapy in peripheral arterial occlusive disease: results from the RELAX trial

PURPOSE: The safety and efficacy of increasing doses of intraarterial reteplase monotherapy and reteplase/abciximab combination therapy were examined in patients with acute peripheral arterial occlusive disease (PAOD). The primary endpoint of this analysis was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) investigators. MATERIALS AND METHODS: The RELAX trial was a prospective, dose-escalating safety trial of reteplase monotherapy (0.1, 0.2, 0.5, or 1.0 U/h) and reteplase/abciximab combination therapy (0.25-mg/kg bolus and 0.125 micro g/kg/min abciximab in addition to each reteplase regimen) for patients with acute or subacute clinical deterioration of PAOD. Reteplase was administered intraarterially to 74 patients; 38 patients were also administered intravenous abciximab for the duration of reteplase infusion. Protocol-specified angiograms were obtained at 6 and 20 hours or for clinical need. Each angiogram was assessed for volume of thrombus dissolved and for arterial patency. The primary safety endpoint (TIMI major bleeding) was assessed at discharge and at day 7. Clinical endpoints were assessed at discharge and at days 30 and 90. RESULTS: Major bleeding occurred with similar frequency in patients treated with and without abciximab (15% of the pooled patients receiving reteplase monotherapy and 20% of patients receiving reteplase/abciximab combination therapy). There were no intracranial hemorrhagic events in the 74 patients. Reteplase doses of at least 0.2 U/hour were effective at dissolving thrombus and restoring patency. There was no clear dose-response relationship for reteplase. However, the addition of abciximab reduced the occurrence of distal embolic events requiring intervention (5% vs. 31%; P =.014). CONCLUSIONS: Over the range of reteplase doses studied for peripheral arterial thrombolysis, there were no significant differences in safety or efficacy. However, the addition of intravenous abciximab to reteplase was associated with a decreased rate of distal embolic events without a significant increase in the risk of hemorrhagic complications. Further investigation is needed to define the role of abciximab in catheter-directed thrombolysis with reteplase for PAOD.     

Catheter-directed thrombolytic therapy in peripheral artery occlusions: combining reteplase and abciximab

OBJECTIVE: The goal of this study was to assess the safety and efficacy of combination therapy consisting of the third-generation plasminogen activator reteplase and the glycoproteins IIb and IIIa platelet receptor antagonist abciximab for thrombolysis in peripheral artery occlusive disease. This two-center experience focused on immediate thrombolytic success, thrombolysis time, complication rate, and 30-day patency rate. SUBJECTS AND METHODS: Fifty patients with arterial occlusive disease (age range, 40-96 years; mean age, 69 years) were prospectively enrolled at two centers. Eighteen patients (36%) had native artery thromboses, and 32 patients (64%) had graft thromboses. Catheter-directed intraarterial thrombolytic infusion of reteplase (average dose, 0.51 U/hr; range, 0.25-1 U/hr) was combined with IV infusion of abciximab (bolus, 0.25 mg/kg of body weight; 12-hr infusion, 0.125 microg/kg of body weight per minute). Nontherapeutic heparin (100-400 U/hr) was given intraarterially during the thrombolytic infusion. RESULTS: Complete thrombolysis was achieved in 89% of the patients with native artery occlusions and 94% of the patients with graft occlusions for an overall rate of 92%. The average thrombolysis time was 20.7 hr (range, 4-41 hr) with a mean reteplase dose of 12.1 U (range, 2-23 U). Major hematoma occurred in 12% of the patients, with an average blood transfusion of 3.1 U of packed RBC (range, 1-11 U), and correlated to increased thrombolysis time and dose. No intracranial hemorrhage occurred. The 30-day primary patency rate was 92%. Two patients (4%) underwent amputation, including one major amputation (2%), within 30 days of thrombolysis. CONCLUSION: The combination of reteplase and abciximab in catheter-directed arterial thrombolysis is feasible and effective. Results of this combination therapy suggest acceptable thrombolysis times and doses with tolerable complication rates. Which patient group might benefit the most from combination therapy and the long-term results of combination therapy still need to be determined.     

Treatment of peripheral arterial obstruction with streptokinase: results in arterial vs graft occlusions

A retrospective study of the efficacy of local low-dose intraarterial streptokinase for the treatment of peripheral arterial occlusion was performed in 60 cases. The results of treatment of occlusion of native arterial and arterial graft occlusions were compared. Twenty-two (73%) of 30 cases of arterial occlusion showed complete or partial angiographic resolution, compared with 16 (53%) of 30 cases of arterial graft occlusion. Ten (71%) of 14 patients with venous arterial grafts were successfully treated vs only six (38%) of 16 patients with prosthetic arterial grafts. These results suggest that streptokinase is an effective fibrinolytic agent for the treatment of arterial occlusion and arterial graft occlusion. Its effectiveness in arterial graft obstruction is comparatively low, although patients with venous grafts respond much more favorably than those with synthetic conduits.     

Intraarterial catheter thrombolytic therapy for acute peripheral arterial occlusions.

Intraarterial thrombolytic therapy was performed in 36 patients with acute arterial occlusions of the extremities. Intraarterial thrombolytic therapy was effective in 19 of 24 patients (79.2%) with embolic occlusions. However, the results were poor in patients who had multiple arterial occlusions including those at sites other than the extremities. Only four of 12 patients (33.3%) with thrombotic occlusions had good initial technical results. Six patients died shortly after the thrombolytic procedure, and seven patients underwent amputation. The long-term patency rate of 21 patients who were treated successfully was 92.7% after one year and 74.6% after five years. Intraarterial catheter thrombolytic therapy was effective for embolic occlusion even when more than six hours had elapsed from the onset of symptoms. The indications for thrombotic occlusions may be limited, since associated marked atherosclerotic change was often present.     

Thrombolysis of acute peripheral arterial and venous occlusions with tenecteplase and eptifibatide: a pilot study

PURPOSE: To prospectively assess the feasibility, risk profile, and effect on fibrinogen levels of combination tenecteplase (TNK) and eptifibatide in transcatheter thrombolysis for peripheral arterial and venous thromboocclusive disease. MATERIALS AND METHODS: Sixteen consecutive patients (seven men, nine women) seen at our institution between March and August 2002 with arterial (n = 11) or venous (n = 5) thromboocclusive disease were treated with TNK (5-mg bolus and 0.25-mg/h infusion) and eptifibatide (180- micro g/kg bolus and 1- micro g/kg/min infusion). Informed consent was obtained. Technical success was defined as restoration of antegrade flow and more than 95% removal of thrombus. Clinical success in arterial cases was defined as immediate limb salvage and relief of ischemic rest pain, and in venous cases as resolution or improvement in extremity pain and swelling. Major bleeding was defined as an intracranial bleeding episode, bleeding resulting in death, or bleeding requiring transfusion, surgery, or cessation of thrombolytic therapy. RESULTS: Technical success was achieved in 10 of 11 arterial cases (91%) and in four of five venous cases (80%). Clinical success was achieved in nine of 11 arterial cases (82%) and in four of five venous cases (80%). The mean duration of thrombolysis was 12.1 hours +/- 5.8 (range, 2-22 hours), requiring a total TNK dose of 8.0 mg +/- 1.5 (range, 4.0-10.5). A major bleeding episode occurred in one of 16 patients (6.3%) as a result of slow oozing from a femoral groin access site and required transfusion of 2 U of packed red blood cells. There were no deaths, intracranial hemorrhages, remote sites of bleeding, or minor bleeding complications. The serum fibrinogen level decreased to a mean of 59.3% +/- 34.6 of baseline. CONCLUSION: In this initial study, the combination of TNK and eptifibatide was shown to be feasible for peripheral arterial and venous thrombolysis.     

Thrombolysis of peripheral arterial and graft occlusions: improved results using high-dose urokinase

Ninety-three thromboembolic occlusions of peripheral arteries or grafts in 85 patients were treated with high-dose urokinase by direct intraarterial infusion. Urokinase was infused at 4000 IU/min until antegrade blood flow was reestablished and then at 1000 or 2000 IU/min until clot lysis was completed. Of the 93 infusions, 75 (81%) resulted in clinical improvement. The infusion therapy was incomplete in nine patients. The mean duration of the 84 completed infusions was 18 +/- 20 hr, the incidence of complete clot lysis was 83%, and the incidence of clinical improvement was 89%. Significant bleeding, requiring transfusion, occurred during or after four of the urokinase infusions (4%). Other complications included distad clot migration, thrombus formation on the catheter, revascularization phenomena, oliguria, skin rash, pseudoaneurysm, balloon rupture during angioplasty, and vascular spasm. There were no instances of drug resistance or adverse drug reactions. These results indicate that an initially high-dose urokinase regimen accomplishes more rapid recanalization, a higher incidence of total clot lysis, and produces fewer complications than the standard low-dose streptokinase regimen.     

Bleeding complications associated with the use of rt-PA versus r-PA for peripheral arterial and venous thromboembolic occlusions

This article analyzes the early experience with alteplase (rt-PA) and reteplase (r-PA) to identify noteworthy differences in bleeding and to determine correlations with dosage, concomitant anticoagulation, and duration of infusion. A retrospective review of the medical records was unavailable for the initial 82 patients who were treated with either rt-PA (44) or r-PA (38) for peripheral arterial or venous occlusions after urokinase therapy. Successful recanalization was achieved in 31/44 (70%) of the patients treated with rt-PA and in 34/38 (89%) of the patients treated with r-PA. Significant bleeding was documented in 20/44 (45%) of the rt-PA-treated patients (including 14 transfusions) versus 3/38 (8%) of the r-PA-treated patients (3 transfusions). Concomitant anticoagulation with either preceding warfarin (international normalized ratio > 1.1) or a bolus of heparin at the outset of the infusion was associated with significant bleeding in 13/17 (76%) of the rt-PA-treated patients (including 9 transfusions) versus 0/17 in the r-PA-treated patients. No significant correlation between either mean dose or total dose and bleeding was shown for either drug. Early experience indicates that r-PA is at least as effective as rt-PA for the thrombolysis of peripheral arterial and venous occlusions. It also appears that r-PA is less likely than rt-PA to be associated with significant bleeding during such infusions, especially if the patient is concomitantly anticoagulated.     

Initial experience with the combination of reteplase and abciximab for thrombolytic therapy in peripheral arterial occlusive disease: a pilot study.

PURPOSE: To report the efficacy of catheter-directed thrombolysis with a combination of a thrombolytic agent (reteplase) and a glycoprotein (GP) IIb/IIIa platelet receptor antagonist (abciximab) in peripheral arterial occlusive disease. MATERIALS AND METHODS: Fifteen patients with lower extremity arterial thromboses (age range, 40-96 y; mean, 73 y) were prospectively enrolled in a protocol approved by the Institutional Review Committee. Nine patients had native arterial occlusions, three (33%) of whom had subacute symptoms (>14 d) and one of whom had chronic symptoms (>3 mo). Four patients had acute arterial graft thromboses. Two patients with lower extremity bypass grafts presented with subacute limb ischemia. All patients received catheter-directed infusion of reteplase (0.5 U/h) in combination with intravenous administration of abciximab (0.25-mg/kg bolus followed by 0.125 microg/kg/min infusion) for 12 hours without systemic heparinization. The thrombolytic success was studied by Doppler ultrasonography (US) and angiography. RESULTS: Complete thrombolysis and clinical success was achieved in 14 of the 15 patients (93%). One patient with unsuccessful thrombolysis underwent major amputation. The mean thrombolysis time per Doppler US procedure was 6.8 hours (range, 2-30 h). Angiographic patency was achieved at a mean of 17.5 hours (range, 4-36 h) corresponding to a mean dose of reteplase of 8.8 U. The mean increase in ankle-brachial index was 0.52 (range, 0-0.9). No major hemorrhagic complications occurred. The 30-day primary patency rate was 93%. CONCLUSION: The combination of reteplase and abciximab in catheter-directed arterial thrombolysis is feasible and effective. This combination therapy pilot study suggests short thrombolysis times and minimal adverse effects in catheter-directed thrombolytic therapy for peripheral arterial occlusive disease.     

Prourokinase versus urokinase for recanalization of peripheral occlusions, safety and efficacy: the PURPOSE trial.

BACKGROUND: The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase. METHODS: A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion. RESULTS: Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage. CONCLUSIONS: The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.     

Dye laser-assisted angioplasty with multifiber catheters: short-term results in the treatment of 29 peripheral arterial occlusions

The use of pulsed dye laser energy for angioplasty offers the possibility of ablating atherosclerotic plaques without thermal damage to the adjacent arterial wall. However, to be of value, systems that deliver the energy safely and effectively are required. We tested multifiber catheters in 504-nm pulsed dye laser angioplasty for treatment of peripheral arterial occlusions. Flexible multifiber catheters consist of 12 (7-French) and 19 (9-French) concentrically arranged 200-microns quartz fibers allowing guidewire-directed use. Laser-assisted angioplasty was performed in 2- to 13-cm- (mean, 7.5-cm) long occlusions of iliac (six) and femoropopliteal (23) arteries in patients with symptomatic occlusive vascular disease. Angiograms were obtained before and after laser ablation, after subsequent balloon dilatation, and if signs or symptoms indicated restenosis, during follow-up. The laser procedure was impossible to perform in three (10%) of 29 patients; this was related to unsuccessful passage of the wire in one patient and to inability to advance the laser catheter across the lesion in two patients. In one other patient, reocclusion occurred 1 day after angioplasty. Stand-alone laser angioplasty relieved residual stenosis of less than 30% in six (26%) of 23 femoropopliteal arteries, making balloon dilatation dispensable. Immediate clinical improvement was achieved in 26 (90%) of 29 patients. Laser treatment caused no perforation and no embolization, but minor dissections occurred in 36% of the patients. Our experience suggests that pulsed dye laser angioplasty via multifiber catheters converts arterial occlusions into stenoses. With the exception of angioplasty in distal femoropopliteal arteries, additional balloon dilatation is necessary to complete recanalization.     

Hepatic arterial port systems for treatment of liver metastases: factors affecting patency and adverse events

PURPOSE: To assess the outcome of interventional hepatic arterial port placement in a prospective phase II trial. MATERIALS AND METHODS: One-hundred five consecutive patients were included in this study. Primary endpoint was port patency; secondary endpoints were complications, toxicity, response, and progression free and overall survival. Seventy-eight patients presented with liver metastasis only, 6 patients had additional minor extrahepatic disease, and 21 patients had no evidence of disease after liver resection, laser-induced thermotherapy, or computed tomography (CT)-guided interstitial brachytherapy of liver metastasis. Exclusive access route was the femoral artery. Subgroup analysis compared either 4-F catheters (n = 58) to 2.2-F (n = 33) and 2.7-F (n = 20) microcatheters or different strategies in anatomic variants of the celiac branch: neglect (n = 10) or embolization of minor hepatic feeders (n = 11), splenic arterial port (n = 8), double port (n = 7). RESULTS: Technical success was 99%. Assisted port patency after 6 months was 93%. Complications demanding port revisions were significantly lower in patients receiving 4-F versus 2.2-F and 2.7-F systems (P <.001), with disconnection as the major problem with use of microcatheters. Hepatic artery thrombosis occurred in 10 patients (9%), with successful lysis in two patients. With use of 4-F and 2.2-F catheters, there was no difference with respect to catheter occlusion or hepatic thrombosis. No differences were noted in complications or outcome applying four different strategies in celiac branch variants. In a subgroup of patients receiving folinic acid/5-fluorouracil (170 mg/600 mg; 10% dose escalation per cycle) for 5 days every 4 weeks only 15% experienced Grade 3 toxicity. Patients with liver metastasis and salvage therapy demonstrated progression-free survival of 63% after 6 months and a median survival of 16 months. CONCLUSION: Interventional placement of hepatic arterial port systems may overcome frequent hepatic arterial chemotherapy failures as encountered in all published major trials on hepatic arterial infusion.     

Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events

PURPOSE: To prospectively evaluate tenecteplase (TNK) for thrombolysis in acute lower-limb ischemia. MATERIALS AND METHODS: Forty-three consecutive limbs in 37 patients (15 male, 22 female) were treated for acute lower-limb ischemia. Group 1 included 22 limbs treated with TNK infusion of 0.25 mg/h and group 2 included 21 limbs treated with TNK at 0.125 mg/h. Technical success was defined by 95% clearing of thrombus, and clinical success was defined by Society of Interventional Radiology category for acute ischemia of +1. Complications were ranked by severity and relation to TNK administration. Logistic regression, Student t test, and analysis of variance were performed. RESULTS: TNK infusions averaged 24 hours in duration (SD, 13 h), with means of 20 hours in group 1 and 27 hours in group 2 (P = .071). Technical success was achieved in 84% of limbs (36 of 43): 82% in group 1 (18 of 22) and 86% in group 2 (18 of 21; P = .827). The SIR ischemia category improved (ie, +1) in 86% of limbs (37 of 43), stayed the same (ie, category 0) in 12% of limbs (five of 43), and worsened (ie, -1) in 2% of limbs (one of 43). TNK-related complications were seen in 12% of limbs (n = 5) and were correlated with percentage decrease in fibrinogen level, initial TNK bolus, and abciximab administration (P = .001, P < .001, and P = .036, respectively). Initial TNK boluses of 1.5 mg or less were associated with fewer complications than boluses of 3-5 mg (P = .045). The percentage decrease in fibrinogen level in group 1 was 23% (SD, 29%), compared with 7% in group 2 (SD, 20%; P = .045). There was a 7% incidence of major bleeding complications (n = 3) and no intracranial hemorrhages. CONCLUSIONS: Treatment of acute lower-limb ischemia with TNK infusion at 0.25 mg/h and 0.125 mg/h is associated with similar success and complication rates. TNK-related complications correlated with initial TNK bolus, abciximab treatment, and percent decrease in fibrinogen level. The initial TNK bolus dose should be limited to 1.5 mg.     

Local intraarterial urokinase thrombolysis of acute ischemic stroke with or without intravenous abciximab: a pilot study

PURPOSE: One of the most important prognostic factors in the thrombolytic treatment of acute ischemic stroke is the time to recanalization. To shorten the recanalization time, an antiplatelet agent, abciximab (platelet glycoprotein receptor IIb/IIIa antagonist), was administered intravenously before the initiation of local intraarterial urokinase thrombolysis. The purpose of this study was to evaluate the effectiveness and safety of this combined therapy. MATERIALS AND METHODS: A total of 26 patients with acute ischemic stroke (National Institutes of Health Stroke Scale score >10) were enrolled in this study. In the earlier phase of this study, conventional local intraarterial urokinase thrombolysis was performed in 16 patients (urokinase group). In the later phase, combined use of intravenous abciximab and local intraarterial urokinase thrombolysis was performed in 10 patients (urokinase + abciximab group). Recanalization rate (Thrombolysis in Myocardial Infarction grade >or=2), total amount of urokinase used, incidence of symptomatic hemorrhage, and better functional outcome rate (modified Rankin scale 相似文献   

调强放疗联合时辰化疗治疗局部进展期鼻咽癌的近期疗效及不良反应

目的 比较时辰化疗与常规化疗联合调强放疗在局部进展期鼻咽癌患者治疗过程中的不良反应、免疫功能、近期疗效。方法 选取2015年7月至2017年4月在贵州医科大学附属肿瘤医院初治局部进展期鼻咽癌患者159例,采用简单随机分组法,前瞻性将159例初治局部进展期鼻咽癌患者随机分为时辰化疗组与常规化疗组,前者采用时辰化疗模式给药,后者采用常规模式给药,两组均采用调强放射治疗,评价近期疗效及观察不良反应。结果 时辰化疗组与常规化疗组近期疗效完全缓解（CR）、部分缓解（PR）、稳定（SD）、进展（PD）差异无统计学意义（P>0.05）,两组有效率（CR+PR）差异无统计学意义（P>0.05）;时辰化疗组的白细胞减少（Z=-2.222,P<0.05）、中性粒细胞减少（Z=-1.999,P<0.05）、呕吐（Z=-2.298,P<0.05）、口腔黏膜炎（Z=-3.571,P<0.05）发生率低于常规化疗组,差异有统计学意义;时辰化疗组CD16+56+淋巴细胞计数高于常规化疗组（Z=-2.332,P<0.05）。结论 时辰化疗作为一种新的治疗模式,与调强放疗联合可在不降低临床疗效的同时减轻治疗相关不良反应的发生率及严重程度,减轻免疫抑制,值得临床推广及应用。