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晚期尤因肿瘤的异基因和自体干细胞移植。欧洲多中心研究EICESS两个中心长期随访后的最新情况。德国杜塞尔多夫大学医学中心和奥地利维也纳圣安娜儿童医院的干细胞移植项目。

Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria.

作者信息

Burdach S, van Kaick B, Laws H J, Ahrens S, Haase R, Körholz D, Pape H, Dunst J, Kahn T, Willers R, Engel B, Dirksen U, Kramm C, Nürnberger W, Heyll A, Ladenstein R, Gadner H, Jürgens H, Go el U

机构信息

Division of Pediatric Hematology/Oncology, Children' s Hospital Medical Center, Martin Luther University Halle-Wittenberg, Halle, Germany.

出版信息

Ann Oncol. 2000 Nov;11(11):1451-62. doi: 10.1023/a:1026539908115.

Abstract

BACKGROUND

An update of results from the High Risk Protocol of the Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centers of Düsseldorf and Vienna. In order to evaluate a possible therapeutic benefit after allogeneic SCT in patients with advanced Ewing tumors (AET), we compared outcome after autologous and allogeneic stem-cell transplantation (SCT).

PATIENTS AND METHODS

We analyzed 36 patients treated with the myeloablative Hyper-ME protocol (hyperfractionated total body irradiation, melphalan, etoposide +/- carboplatin) between November 1986 and December 1994. Minimal follow-up for all patients was five years. All patients underwent remission induction chemotherapy and local treatment before myeloablative therapy. Seventeen of thirty-six patients had multifocal primary Ewing's tumor, eighteen of thirty-six had early, multiple or multifocal relapse, one of thirty-six patients had unifocal late relapse. Twenty-six of thirty-six were treated with autologous and ten of thirty-six with allogeneic hematopoietic stem cells. We analyzed the following risk factors, that could possibly influence the event-free survival (EFS): number of involved bones, degree of remission at time of SCT, type of graft, indication for SCT, bone marrow infiltration, bone with concomitant lung disease, age at time of diagnosis, pelvic involvement, involved compartment radiation, histopathological diagnosis.

RESULTS

EFS for the 36 patients was 0.24 (0.21) +/- 0.07. Eighteen of thirty-six patients suffered relapse or died of disease, nine of thirty-six died of treatment related toxicity (DOC). Nine of thirty-six patients are alive in CR. Age > or = 17 years at initial diagnosis (P < 0.005) significantly deteriorated outcome. According to the type of graft, EFS was 0.25 +/- 0.08 after autologous and 0.20 +/- 0.13 after allogeneic SCT. Incidence of DOC was more than twice as high after allogeneic (40%) compared to autologous (19%) SCT, even though the difference did not reach significance (P = 0.08, Fisher's exact test).

CONCLUSIONS

Because of the rather short observation period. secondary malignant neoplasms (SMN) may complicate the future clinical course of some of our patients who are currently viewed as event-free survivors. EFS in AET is not improved by allogeneic SCT due to a higher complication rate. The patient group was to small to analyze for a possible graft-versus-tumor effect.

摘要

背景

对在杜塞尔多夫和维也纳的儿科干细胞移植中心开展的Meta-EICESS研究高风险方案的结果进行更新。为了评估晚期尤因肿瘤(AET)患者接受异基因造血干细胞移植(SCT)后可能的治疗益处,我们比较了自体和异基因干细胞移植后的结局。

患者和方法

我们分析了1986年11月至1994年12月期间接受清髓性Hyper-ME方案(超分割全身照射、美法仑、依托泊苷+/-卡铂)治疗的36例患者。所有患者的最短随访时间为5年。所有患者在清髓性治疗前均接受了缓解诱导化疗和局部治疗。36例患者中有17例有多灶性原发性尤因肿瘤,36例中有18例有早期、多发或多灶性复发,36例中有1例有单灶性晚期复发。36例中有26例接受了自体造血干细胞治疗,36例中有10例接受了异基因造血干细胞治疗。我们分析了以下可能影响无事件生存期(EFS)的危险因素:受累骨的数量、SCT时的缓解程度、移植物类型、SCT的指征、骨髓浸润、伴有肺部疾病的骨、诊断时的年龄、盆腔受累情况、受累区域放疗、组织病理学诊断。

结果

36例患者的EFS为0.24(0.21)±0.07。36例患者中有18例复发或死于疾病,36例中有9例死于治疗相关毒性(DOC)。36例患者中有9例在完全缓解(CR)状态下存活。初始诊断时年龄≥17岁(P<0.005)显著恶化结局。根据移植物类型,自体SCT后的EFS为0.25±0.08,异基因SCT后的EFS为0.20±0.13。异基因SCT后的DOC发生率(40%)是自体SCT(19%)的两倍多,尽管差异未达到显著性(P=0.08,Fisher精确检验)。

结论

由于观察期较短,继发性恶性肿瘤(SMN)可能会使我们目前被视为无事件生存者的部分患者未来的临床病程复杂化。异基因SCT由于并发症发生率较高,并未改善AET患者的EFS。患者组规模太小,无法分析可能的移植物抗肿瘤效应。

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