小剂量肝素预防异基因造血干细胞移植后肝静脉阻塞症

目的探讨小剂量肝素预防以白消安／环磷酰胺（BU／CY）为预处理的异基因造血干细胞移植（allo-HSCT）后肝静脉阻塞症（VOD）的安全性和有效性,以及肝素使用的最佳时间跨度。方法1997年4月至2005年12月,134例患者在本院进行了allo—HSCT。所有患者均接受标准BU／CY或以此为基础的预处理方案,以肝素100IU·kg^-1·d^-1持续24h静滴预防VOD。分别比较血缘供者和非血缘供者移植、移植前肝功能正常与否、肝素使用时间不同组的VOD发生率。结果134例患者全部顺利植活,中性粒细胞〉0．5×10^9／L和血小板〉20×10^9／L的中位数时间分别为移植后12（9～28）d和20（6～65）d。其中118例白血病患者中97例（82．2％）于移植后100d无白血病生存。134例患者无一例发生VOD,其中包括47例非亲缘供者移植（骨髓移植34例,外周血干细胞移植8例,脐血5例）和肝功能异常组40例,肝素使用时间不同的两组亦无VOD发生。未有定期检测凝血酶原时间、部分活化凝血活酶时间组与监测组比较,临床出血情况并无明显加重。结论单一小剂量肝素预防以BU／CY为预处理方案的allo-HSCT后VOD安全有效,肝素使用时间跨度缩短为移植前7d至移植后14d并不影响其预防效果。     

肝素联合前列腺素E1预防造血干细胞移植后肝静脉阻塞症

目的 探讨在异基因造血干细胞移植(Allo-HSCT)中使用肝素联合前列腺素E1(PGE1)预防肝静脉阻塞症(HVOD)的疗效和不良反应.方法 100例造血干细胞移植患者,男62人,女38人,其中位年龄30岁(2～62岁),其中血液系统恶性肿瘤85例,重型再生障碍性贫血13例,重症肌无力2例.所有患者均采用肝素联合PGE1预防HVOD.结果 100例造血干细胞移植患者中除3例非血缘脐血移植患者未植入外其余患者均获得植入,本组HVOD的发生率2.0%.结论 肝素联合PGE1可用于造血干细胞移植中预防HVOD,疗效好,副作用小,价格低廉,是一个安全,值得推广的预防方案.     

非清髓异基因造血干细胞移植治疗恶性血液病临床分析

目的:观察非清髓异基因造血干细胞移植(NST)治疗恶性血液病的疗效及并发症的处理。方法:对33例恶性血液病患者施行NST并随访观察。预处理方案应用氟达拉滨30mg.m-2.d-1(-7～-2d),马利兰4mg.kg-1.d-1(-6～-5d),环磷酰胺350mg.m-2.d-1(-3～-2d),HLA不全相合者加用抗淋巴细胞球蛋白(ALG)750mg/d(-2～-1d)。移植物抗宿主病(GVHD)预防应用环孢素A(CsA)和骁悉(MMF)。应用美司那、大量水化、碱化尿液预防出血性膀胱炎。应用凯时(前列腺素E1)预防肝静脉闭塞病(VOD)。结果:全部患者均成功植入,造血重建速度快。中性粒细胞0.5×109/L的中位时间是+13(+10～+16)d,血小板20×109/L的中位时间是+12(+9～+25)d。3例患者在+100d左右出现间质性肺炎,血CMV-DNA阳性,应用更昔洛维抗病毒等治疗后均痊愈。17例患者发生急性移植物抗宿主病(aGVHD)(51.5%),Ⅰ度患者10例(30.3%),Ⅱ度患者5例(15.2%),Ⅲ度患者2例(6.06%)。有20例患者出现慢性移植物抗宿主病(cGVHD)(64.5%),其中局限型15例(48.4%),广泛型5例(16.1%)。有3例患者出现VOD(9.1%),5例患者出现出血性膀胱炎(15.2%),经积极治疗均有效控制。中位随访37(2.5～58.0)个月,现存活24例(72.7%),9例死亡(27.3%),5例疾病复发(15.2%)。9例死亡患者中7例死于GVHD,2例死于疾病复发。结论:NST植入可靠,造血重建快,复发率低,移植相关并发症感染、出血性膀胱炎、VOD发生率低,治疗安全、有效。但GVHD发生率较高,是导致死亡的主要原因。     

儿童重型β-地中海贫血造血干细胞移植后肝静脉闭塞病防治的临床观察

目的:观察肝素联合前列地尔脂质微球体(凯时)和人血白蛋白在防治儿童重型β-地中海贫血造血干细胞移植后肝静脉闭塞病(HVOD)中的作用。方法:对38例重型β-地中海贫血患儿,年龄在2~14岁之间,平均年龄为6.1岁,共进行46例次造血干细胞移植,从-3d开始应用肝素, 1d开始应用前列地尔脂质微球体和人血白蛋白预防HVOD,观察其临床效果。结果:46例次的造血干细胞移植过程中有20例发生程度不一的肝静脉闭塞病。肝素、前列地尔脂质微球体和人血白蛋白联合应用过程中未观察到明显的毒副作用。结论:肝素联合前列地尔脂质微球体和人血白蛋白在预防儿童重型β-地中海贫血造血干细胞移植后肝静脉闭塞病是有效的。     

前列腺素E1和丹参对老年人血小板聚集率影响的比较

目的：观察比较前列腺素E1脂微球载体制剂（Lipo PGE1)和丹参对老年人血小板聚集率的影响。方法：将38例老年心、脑血管疾病患，在均衡原则下随机分成两组。一组予前列腺素E1脂微球载体制剂（Lipo PGE1)10μｇ／天，共１４天，另一组予丹针剂12ml/天，共14天，比较两对血小板聚集率的影响。结果：前列腺素E1组降低血小板聚集（P＜0．01），丹参组降低血小板聚集率（P＜0．05）。结论：前列腺素E1脂微球载体制剂（Lipo PGE1)和丹参都能抑制血小板聚集，而Lipo PGE1更有效，无一例发生静脉炎。但从效价比出发，丹参更适合国情。     

异基因外周血造血干细胞移植治疗恶性血液病26例临床观察

目的:观察allo-PBSCT对恶性血液病的临床疗效。方法:采用经G-CSF动员的同胞HLA相合的异基因外周血干细胞移植,预处理方案采用改良的Bu/Cy方案;GVHD的预防采用CsA联合MMF、MTX,部分患者加用ALG;PGE1联合复方丹参预防VOD。结果:输入CD34+细胞数5.988×106/kg受者体重,全部患者均成功植入,中性粒细恢复至0.5×109/L所需天数为11.68d,血小板恢复至20×109/L所需时间为12.57d,接受CD34+细胞数>5×106/kg者与<5×106/kg者,中性粒细胞与血小板恢复时间差异无统计学意义(P>0.01);Ⅰ~ⅢaGVHD发生率为30.77%,cGVHD的发生率为69.23%,HC发生率11.54%,VOD发生率为0;总死亡率为15.38%,600dDFS为58.96%。结论:allo-PBSCT能提供更快的造血功能恢复,aGVHD的发生率无增加,而cGVHD的发生率较高;allo-PBSCT是治疗恶性血液病较好的治疗手段。     

氟达拉滨联合静脉马利兰的预处理方案治疗髓系恶性血液病的临床研究

目的:评价氟达拉滨(Flu)联合静脉马利兰(Bu)的预处理方案在髓系恶性血液病患者异基因造血干细胞移植(allo-HSCT)中的疗效及静脉Bu的最佳剂量。方法:45例接受allo-HSCT的髓系恶性血液病患者,预处理方案主要采用Bu3.2mg·kg-1.d-1×2～4d,Cy40～50mg/kg×2d,Flu30mg.m-2.d-1×3d,Ara-C2g.m-2.d-1×3d,无关供者移植同时加用兔抗人血清免疫球蛋白(ATG)2.5mg/kg×4d。按静脉Bu用量进一步分为2d组17例,3d组18例,4d组10例。结果:预处理过程无严重不良事件发生,无肝静脉闭塞病(VOD)发生,Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)9例(20%),100d移植相关死亡(TRM)1例(2.2%),3年TRM15例(33.3%),3年累计复发3例(6.7%),3年无病生存率(DFS)和3年总体生存率(OS)分别为(60.5±7.5)%和(62.2±7.2)%。与Bu2d组和3d组比较,4d组患者的慢性GVHD的发生率显著增高,TRM有增高趋势;OS显著降低,DFS有降低趋势。结论:Flu联合静脉Bu的预处理方案治疗髓系恶性血液...     

异基因外周血干细胞移植治疗白血病的临床观察

目的:观察同胞供者异基因外周血干细胞移植(allo-PBSCT)治疗白血病的疗效及并发症.方法:分析11例白血病患者行同胞供者HLA相合allo-PBSCT治疗的临床资料.供者干细胞动员用粒细胞集落刺激因子(G-CSF),用CS-3000血细胞分离机采集外周血干细胞.患者用改良马利兰加环磷酰胺(Bu/CY)为预处理方案,用环孢菌素A(CSA)+短程甲氨蝶呤(MTX)+霉酚酸酯(MMF)方案预防移植物抗宿主病(GVHD),用前列腺素E1(凯时)+低分子肝素预防肝静脉闭塞病(HVOD),用美司钠预防出血性膀胱炎(HC).结果:获得单个核细胞数(MNC)的中位数为8.3(4.5～13.0)×108/kg;CD34+细胞计数的中位数为6.2(2.4～12.4)×106/kg.10例患者获得造血重建,白细胞和血小板植活的中位数时间均为15(13 ～ 18)d;1例患者干细胞未植入.并发症:发生感染11例,GVHD 8例,HVOD 3例,HC 1例.中位随访15.5(1 ～39)个月,生存率为63.6％(7例),无病存活率为54.5％(6例);4例死亡.结论:同胞供者allo-PBSCT是治疗白血病一种有效手段,移植相关并发症主要为感染、GVHD、HVOD.     

非清髓性自体外周血造血干细胞移植治疗难治性自身免疫病五年随访

目的 探讨非清髓性自体外周血造血干细胞移植(NAST)治疗难治性自身免疫病(AD)的远期疗效.方法 总结5例接受NAST的AD患者移植后的随访情况.非清髓性预处理方案:移植前2d阿糖胞苷(200mg·kg-1·d-1)及环磷酰胺(40 mg· kg-1·d-1),均为静脉滴注.评价患者移植前后的相关症状体征的改变及远期并发症,流式细胞仪检测免疫功能的变化.结果 5例患者均成功植入.白细胞总数恢复正常的平均时间12d,血小板＞100×109/L的平均时间为10d,血红蛋白＞120 g/L的平均时间为22 d.随访中,NAST后5例患者临床症状和体症明显缓解,淋巴细胞亚群检测显示:CD4+及CD4+/CD8+均恢复正常.1例男性患者移植4年后妻子正常受孕并产下一健康女婴.4例女性均恢复正常工作与生活.结论 与经典的清髓性HSCT治疗AD比较,NAST造血重建快,远期疗效确切.AD患者NAST治疗后生活质量好于清髓性HSCT.     

脂微球前列腺素E_1联合长春西汀治疗椎—基底动脉缺血性眩晕疗效观察

目的观察脂微球前列腺素E_1联合长春西汀治疗椎—基底动脉缺血性眩晕的疗效。方法 66例椎—基底动脉缺血性眩晕患者,随机分为治疗组及对照组,各33例。治疗组予长春西汀20 mg联合脂微球前列腺素E_110μg静滴,1次/d,共用10 d。对照组予丹参30 ml联合脉络宁30 ml静滴,1次/d,共用10 d。全部病例治疗前后均作经颅多普勒(TCD)检查。结果治疗组痊愈28例、好转3例、无效2例,总有效率为94%;对照组分别为19、5、9例和73%。两组总有效率相比P<0.01。结论脂微球前列腺素E_1联合长春西汀治疗椎—基底动脉缺血性眩晕的效果较好。     

Hematopoietic stem cell transplantation with busulfanthiotepa-cyclophosphamide conditioning for pediatric patients with high-risk acute lymphoblastic leukemia]

Twelve children with high-risk acute lymphoblastic leukemia underwent stem cell transplantation (SCT) with a conditioning regimen consisting of busulfan, cyclophosphamide and thiotepa. Eight of them underwent SCT while in complete remission (CR) and the other 4 while not in CR. Three children underwent HLA-matched related bone marrow transplantation (BMT), 7 HLA-matched unrelated BMT, 1 HLA one-locus-mismatched unrelated cord blood cell transplantation, and 1 autologous peripheral blood stem cell transplantation. Grade II-IV acute GVHD was observed in 3 of the 11 allo-SCT cases, while chronic GVHD was seen in 3 of 9 evaluable cases. None of the 12 cases showed thrombotic microangiopathy, and veno-occlusive disease (VOD) was observed in 3. Nine of the patients are alive and disease-free 6-45 months after diagnosis. The event-free survival rate at 3 years was 72.2% for the 12 patients, including 8 of the 9 who received SCT during CR, and 2 of the 4 who did so while not in CR. The other 3 patients died: 2 of disease progression and 1 of VOD with pneumonia. All of those who died had undergone unrelated BMT.     

Retrospective multivariate analysis of hepatic veno-occlusive disease after blood or marrow transplantation: possible beneficial use of low molecular weight heparin

This retrospective cohort study of 462 consecutive adult allogeneic and autologous blood or marrow transplantation (BMT) patients compared the incidence of hepatic veno-occlusive disease (VOD) after BMT with three prophylactic regimens. Patients receiving heparin (Hep), heparin + prostaglandin E1 (Hep + PGE1) or low molecular weight heparin (LMWH) as a prophylactic VOD regimen were compared to a historical cohort receiving no VOD prophylaxis. Of 462 BMT patients, VOD was diagnosed in 22% (31 of 142) of the no prophylaxis group, 11% (11 of 104) of the Hep, 12% (13 of 110) in the Hep + PGE1 and 4% (four of 106) of the LMWH group (P = 0.0002). VOD was the primary cause of death in 20% (12 of 59). By multivariate logistic regression, independent risk factors for developing VOD were: no VOD prophylactic regimen, unrelated allogeneic BMT, Karnofsky performance score (KPS) < 80 and aspartate aminotransferase (AST) > or =50 U/l. There was no increase in the rate of death due to hemorrhagic events or VOD in any prophylaxis group compared to the control group. Prospective randomized trials of Hep vs LMWH vs placebo are warranted to assess the efficacy of heparin compounds in the prevention of VOD.     

Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial.

Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT.     

Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia

Allogeneic stem cell transplantation (SCT) is one of the most expensive medical procedures. However, only a few studies to date have addressed the costs of HLA-identical sibling transplantation and only one study has reported costs of unrelated transplantation. No recent cost analysis with a proper follow-up period and donor identification expenses is available on related or voluntary matched unrelated donor (MUD) SCT for adult AML or ALL. Therefore, we calculated direct medical (hospital) costs based on 97 adults who underwent HLA-identical sibling bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), and patients who received a graft from a MUD between 1994 and 1999. The average costs per transplanted patient were Euro 98,334 (BMT), Euro 151,754 (MUD), and Euro 98,977 (PBSCT), including donor identification expenses, 2 years follow-up and costs of patients who were not transplanted after they had been planned to receive an allograft. The majority of these costs was generated during the hospitalisation for graft infusion. For MUD transplants, nearly one-third of these costs was spent on the search for a suitable donor. For patients who were alive after 2 years, cumulative expenses were calculated to be Euro 103,509 (BMT), Euro 173,587 (MUD), and Euro 105,906 (PBSCT).     

异基因造血干细胞移植治疗白血病76例临床观察

目的观察不同来源的异基因造血干细胞移植治疗白血病的疗效并探讨主要并发症的处理方案。方法对2001年9月至2007年3月第四军医大学西京医院血液科76例白血病患者行异基因造血干细胞移植治疗,其中慢性粒细胞白血病34例,急性髓性白血病24例,急性淋巴细胞白血病15例,T细胞淋巴瘤/白血病3例。人类白细胞抗原(HLA)全相合的同胞供者57例,1个HLA位点不合同胞供者3例,HLA单倍型半相合同胞供者7例,非血缘供者9例。预处理方案采用改良的马利兰联合环磷酰胺(BUCY)或改良的环磷酰胺联合全身放疗及阿糖胞苷或鬼臼乙叉甙(CyTBI Ara-c/VP-16)方案。采用标准的环孢素A(CsA)联合短期甲氨蝶呤(MTX)方案预防移植物抗宿主病(GVHD);无关供者移植加用抗人胸腺细胞球蛋白,单倍型半相合移植同时加用CD25单克隆抗体。结果96.1%(73/76)获得植入。24.7%(18/73)出现急性GVHD,32.9%(24/73)出现慢性GVHD;合并重症肝静脉闭塞病2例;并发纯红细胞性再生障碍性贫血5例。随访3~72个月,现存活56.6%(43/76),43.4%(33/76)在移植后1~36个月时死亡,19例死于白血病复发,14例死于移植相关并发症。结论多种来源的异基因造血干细胞移植是治疗白血病的有效方法,于慢性粒细胞白血病慢性期、急性白血病缓解期移植效果较好,移植前处于高危难治状态的病例复发率仍较高。     

Positive selection for CD34+ reduces the incidence and severity of veno-occlusive disease of the liver after HLA-identical sibling allogeneic peripheral blood stem cell transplantation

OBJECTIVE: T-cell depletion (TCD), primarily developed to prevent graft-vs-host disease (GVHD), might reduce early liver dysfunction after allogeneic hematopoietic stem cell transplantation. However, no comparative studies have been performed to investigate this. We analyzed the influence of selection for CD34(+) cells on the incidence and severity of hepatic veno-occlusive disease (VOD). PATIENTS AND METHODS: Five hundred and one patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from HLA-identical siblings were included in the present study. Two hundred and ninety patients (59%) were grafted with CD34+ positively selected grafts and 211 (41%) with nonmanipulated grafts. Their mean age was 38 years (range 17-63). All patients had hematological malignancies and 96% were conditioned with combinations either of cyclophosphamide plus total-body irradiation or of cyclophosphamide plus busulphan. Most of the patients received GVHD prophylaxis with methotrexate (MTX) or cyclosporin A. RESULTS: Fifty-two patients (10.4%) developed VOD. VOD was more frequent in patients receiving nonmanipulated grafts (16.1% vs 6.2%; p<0.0009), in those with a Karnofsky score less than 90 (17.5% vs 7.8%; p=0.001), and with the use of MTX for GVHD prophylaxis (14.8% vs 7%; p=0.005). In multivariate analyses, only CD34+ positive selection (p=0.0007) and Karnofsky score (p=0.004) emerged as independent risk factors for VOD. The same effect was observed in the subset of patients with severe VOD. CONCLUSION: These findings show that CD34+ selection not only decreases the incidence of GVHD but also prevents VOD after HLA-identical sibling PBSCT.     

Feasibility and safety of peripheral blood stem cell transplantation from unrelated donors: results of a single-center study

We compared the outcomes in patients receiving unrelated peripheral blood stem cell transplants (PBSCT) with those receiving bone marrow transplants (BMT) in a matched pair analysis. Seventy-four patients with hematological malignancies with HLA-matched (77%) and mismatched (23%) donors were analyzed in this study. Thirty-four patients (45%) were considered as high risk patients. Sixty-eight patients received standard conditioning regimens with Bu/Cy or TBI/Cy. Six patients received an intensified conditioning regimen with the addition of etoposide, thiotepa or melphalan. GVHD prophylaxis consisted of prednisolone, cyclosporine and methotrexate. Groups were matched for patient, donor, transplant characteristics and HLA compatibility. Peripheral blood stem cell collection led to the collection of a higher number of CD34+ and CD3+ cells in comparison to bone marrow collection. Leukocyte engraftment in the PBSCT group occurred in 14 days (median; range 6-26 days) and in the BMT group in 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly. The incidence of grades II-lV acute GVHD in the group of HLA-identical patients was 35% in the PBSCT group and 25% in the BMT group (P < 0.33, log-rank). However, there was a significant difference (P < 0.05, log-rank) in incidence and time to onset of acute GVHD II-IV comparing all patients, including the 17 mismatched transplants. Disease-free survival was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days for PBSC and BMT transplants, respectively. In conclusion, our results indicate that allogeneic PBSCT led to significantly faster leukocyte engraftment but is associated with a higher incidence and more rapid onset of severe acute GVHD comparing all patients, including the 17 mismatched transplants. However, the incidence of severe acute GVHD in HLA-identical patients was not different between the PBSCT and BMT groups.     

Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study

We evaluated 40 patients undergoing high-dose chemo/radiotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) (allogeneic (22), autologous (18)) to determine the safety and feasibility of administering low molecular weight heparin (LMWH) as hepatic veno-occlusive disease (VOD) prophylaxis. Patients received a once daily subcutaneous injection of dalteparin 2500 anti-Xa i.u. commencing the day prior to starting HDCT, and continuing until day +30 post HSCT or hospital discharge, whichever came first. Dosage adjustments were made for patients developing renal failure. All bleeding episodes were recorded and graded and VOD was diagnosed and graded according to Seattle criteria. At 100 days of follow-up, the overall survival and probability of regimen-related mortality were 85 and 15%, respectively. Nine patients developed VOD. The probability of developing VOD post allogeneic and autologous HSCT was 28% (95% CI, 6-45) and 17% (95% CI, 0-32), respectively. VOD was graded as moderate (n=8) and severe (n=1). VOD resolved in all cases except for one patient who died secondary to severe VOD and multiorgan failure. Clinically significant bleeding episodes occurred in three patients; 24 patients developed minor bleeding not requiring specific therapy. All bleeding episodes resolved. These results suggest that LMWH for VOD prophylaxis is safe with a low incidence of serious bleeding events. Whether it is superior to unfractionated heparin, however, is unknown and should be addressed within the context of a randomized controlled trial.     

Increase of interleukin-18 serum levels after engraftment correlates with acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation

Purpose Acute graft-versus-host disease (GvHD) is a constant and severe complication after allogeneic stem cell transplantation regularly involving skin, liver, gut, and lungs. The cytokine interleukin-18 (IL-18) has been shown to increase in patients who develop acute GvHD after bone marrow tranplantation (BMT).Materials and methods Here, we measured IL-18 serum levels after peripheral blood stem cell transplantation (PBSCT) at several characteristic time points in 24 patients (median age 46 years). Patients received a median of 7.3×10⁶/kg bodyweight CD34-positive blood stem cells from HLA-matched family donors (n=5), matched unrelated donors (n=18), and one mismatched unrelated donor. GvHD prophylaxis consisted of cyclosporin A alone or combined with methotrexate and/or mycophenolate mofetil.Results In 14 patients we observed no GvHD or only GvHD grade I whereas ten patients developed GvHD grade II–IV post transplant. Low, intermediate, and high levels of serum IL-18 were found in patients after allogeneic PBSCT independently of GvHD after transplantation. In contrast to GvHD arising after BMT, there was no clear correlation between absolute IL-18 serum levels and GvHD grade after PBSCT. However, the individual time course of IL-18 serum level after engraftment correlates with acute GvHD after PBSCT. In detail, an increase of serum IL-18 of at least 1.6-fold after engraftment is associated with acute GvHD II or higher with a sensitivity of three out of four. Using the 1.6 cut-off for IL-18 increase after engraftment, a specificity of up to 100% can be achieved.Conclusion The time course of IL-18 serum levels might be used for GvHD prediction after PBSCT comparable to absolute serum levels after BMT.S. Scholl and H. G. Sayer contributed equally to this work.     

Outcome of transplantation of highly purified peripheral blood CD34+ cells with T-cell add-back compared with unmanipulated bone marrow or peripheral blood stem cells from HLA-identical sibling donors in patients with first chronic phase chronic myeloid leukemia

Outcomes of highly purified CD34(+) peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (CML) (n = 32) were compared with those of PBSCT (n = 19) and of bone marrow transplantation (BMT) (n = 22) in the HLA-compatible sibling donor setting. Median follow-up was 18 months after CD34(+)-PBSCT and unmanipulated PBSCT and 20 months after BMT. CD34(+)-PBSCT was associated with delayed T-cell immune reconstitution at 3 months and 12 months after transplantation compared with PBSCT (P <.001) or BMT (not significant [NS]). The estimated probability of grades II to IV acute graft-versus-host disease (GVHD) was 60% +/- 13% for the PBSCT group, 37% +/- 13% for the BMT group, and only 14% +/- 8% for the CD34(+)-PBSCT group (CD34-PBSCT versus BMT, P <.01; and CD34-PBSCT versus PBSCT, P <.001). The probabilities for molecular relapse were 88% for CD34(+)-PBSCT, 55% after BMT, and 37% after PBSCT (CD34(+)-PBSCT versus PBSCT, P <.03). Cytogenetic relapse probability was 58% after CD34(+)-PBSCT, 42% after BMT, and 28% after PBSCT (NS). After CD34(+)-PBSCT, 26 of 32 patients received a T-cell add-back. Hematologic relapse occurred in 4 of 22 patients after BMT, in 3 of 19 patients after PBSCT, and in only 1 of 32 patients after CD34(+)-PBSCT. The occurrence of a hematologic relapse in patients receiving CD34(+)-PBSC transplants was prevented by donor leukocyte infusions, which were applied at a median of 4 times (range, 1-7 times) with a median T-cell dose of 3.3 x 10(6) x kg/body weight [at a median] beginning at day 120 (range, 60-690 days). The estimated probability of 3-year survival after transplantation was 90% in the CD34(+)-PBSCT group, 68% in the PBSCT group, and 63% in the BMT group (CD34-PBSCT versus BMT, P <.01; and CD34-PBSCT versus PBSCT, P <.03). Transplantation of CD34(+)-PBSCs with T-cell add-back for patients with CML in first chronic phase seems to be safe and is an encouraging alternative transplant procedure to BMT or PBSCT.