Fröhlich B, Ahrens S, Burdach S, Klingebiel T, Ladenstein R, Paulussen M, Zoubek A, Jürgens H
Klinik für Pädiatrische Hämatologie und Onkologie, Westfälische Wilhelms-Universität, Münster.
Klin Padiatr. 1999 Jul-Aug;211(4):284-90. doi: 10.1055/s-2008-1043801.
Patients (pts) with primary metastatic Ewing tumours (ET) have a poor prognosis for event free survival (EFS) compared to pts with localised disease. Following relapse the prognosis is extremely poor. Therefore these primary metastatic and relapsed pts were piloted for high dose therapy (HDT) for the last years.
Between April 1984 and May 1997, 131 ET pts who underwent HDT were registered in the German CESS/EICESS office: 79 pts with primary metastases and 52 pts with relapsed tumours. After induction therapy, consisting of chemotherapy and local therapy, pts received high dose regimens, mainly based on melphalan and/or etoposide (92%). Stem cell rescue was applied from allogeneic bone marrow (n = 13), autologous bone marrow (n = 17), or peripheral blood stem cells (n = 95). The date of analysis was September 1st, 1998. Outcome was calculated by Kaplan-Meier-analyses.
The median time under study since high dose therapy was 3.7 years. 35/131 pts (26.7%) were in continuous complete remission, 80/131 pts (61.1%) had relapsed or progressed, 11/131 pts (8.4%) died of complications and 5/131 pts (3.8%) presented with secondary malignancies. For the total group of primary metastatic pts, EFS five years after diagnosis was 19% for pts with HDT and 27% for those without (p = 0.9209). The subgroup of pts with primary lung and bone metastases seemed to benefit from HDT (EFS five years after diagnosis: 34% versus 5%, p = 0.0001). Outcome of pts with an early ET relapse (< 2 years) was also improved by HDT (EFS four years after relapse: 17% versus 2%, p = 0.0001).
The total group of primary metastatic ET pts showed no obvious benefit from HDT, based on melphalan and/or etoposide. Pts with metastases to multiple organ systems, and early relapse seemed to benefit from HDT. The value of HDT should be assessed in prospective clinical trials.
与局限性原发性尤因肿瘤（ET）患者相比，原发性转移性ET患者的无事件生存期（EFS）预后较差。复发后的预后极差。因此，在过去几年中对这些原发性转移性和复发性患者进行了高剂量治疗（HDT）的试点。
1984年4月至1997年5月期间，131例接受HDT的ET患者在德国CESS/EICESS办公室登记：79例原发性转移患者和52例复发性肿瘤患者。在由化疗和局部治疗组成的诱导治疗后，患者接受主要基于美法仑和/或依托泊苷的高剂量方案（92%）。采用异基因骨髓（n = 13）、自体骨髓（n = 17）或外周血干细胞（n = 95）进行干细胞救援。分析日期为1998年9月1日。通过Kaplan-Meier分析计算结果。
自高剂量治疗以来的中位研究时间为3.7年。131例患者中有35例（26.7%）持续完全缓解，80例（61.1%）复发或进展，11例（8.4%）死于并发症，5例（3.8%）出现继发性恶性肿瘤。对于原发性转移性患者的总体组，诊断后5年的EFS，接受HDT的患者为19%，未接受HDT的患者为27%（p = 0.9209）。原发性肺和骨转移患者亚组似乎从HDT中获益（诊断后5年的EFS：34%对5%，p = 0.0001）。HDT也改善了早期ET复发（<2年）患者的预后（复发后4年的EFS：17%对2%，p = 0.0001）。
基于美法仑和/或依托泊苷的HDT对原发性转移性ET患者总体组未显示出明显益处。多器官系统转移和早期复发的患者似乎从HDT中获益。HDT的价值应在前瞻性临床试验中评估。
