Laws H J, Burdach S, van Kaick B, Engel B, Dirksen U, Körholz D, Pape H, Kahn T, Merck H, Schmitz M, Heyll A, Dockhorn-Dworniczak B, Jürgens H, Göbel U
Department of Pediatric Hematology and Oncology, Heinrich Heine University Medical Center Düsseldorf.
Strahlenther Onkol. 1999 Oct;175(10):488-94. doi: 10.1007/s000660050059.
The prognosis of Ewing's tumor patients has been improved gradually through cooperative therapy studies, so that meanwhile 55 to 65% of the patients survive relapse-free in the long term. Patients with multifocal primary, early or multiply-relapsed Ewing's tumors have a dismal prognosis. Megatherapy with subsequent stem cell transplantation seems to improve outcome in this patient cohort. Feasibility of this intense megatherapy regimen is crucially dependent on collaboration and multidisciplinary coordination of radiologists, radiotherapists, surgeons and oncologists.
Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (> 200 ml) were excised, as well as lung metastases which could still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity of early regenerating NK-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol.
Of 25 patients treated with megatherapy, 10 patients are still alive with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15 +/- 6 days down to 9 +/- 2 days through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multi-organ failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy.
The complex diagnostic and therapeutic strategy renders and EFS of 34% for a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject.
通过合作治疗研究，尤因肉瘤患者的预后已逐渐得到改善，目前有55%至65%的患者能长期无复发存活。多灶性原发性、早期或多次复发的尤因肉瘤患者预后不佳。大剂量化疗联合后续干细胞移植似乎能改善这一患者群体的预后。这种强化大剂量化疗方案的可行性关键取决于放射科医生、放疗科医生、外科医生和肿瘤内科医生的协作及多学科协调。
自1988年以来，25例患者接受了由美法仑、依托泊苷和全身照射组成的大剂量化疗，随后进行干细胞移植。所有患者均接受6个疗程的诱导治疗。在第四个治疗阶段之前，对初诊时体积较大（>200 ml）的肿瘤以及在第三个化疗阶段后仍能检测到的肺转移灶进行切除。在第五和第六个化疗阶段，患者对所有浸润部位进行局部照射。大剂量治疗后持续的免疫抑制可能会增加复发率。为提高早期再生自然杀伤细胞的增殖和细胞毒活性，大剂量化疗后采用全身IL-2治疗的过继性免疫治疗是治疗方案的一部分。
在接受大剂量化疗的25例患者中，10例患者仍然存活，大剂量化疗后的随访时间为6个月至9年。通过使用粒细胞集落刺激因子（G-CSF）和CD34+选择的干细胞，造血干细胞植入时间从15±6天缩短至9±2天。同时，红细胞和血小板替代时间也缩短了。常见的并发症是粘膜炎和感染。1例患者在发生败血症和多器官功能衰竭后死亡，另1例患者在大剂量化疗4.5年后发生骨髓增生异常综合征。然而，复发仍然是主要的死亡原因。由于25例患者中有21例接受了过继性免疫治疗，因此无法评估IL-2对无事件生存期的影响。
对于预后不佳的患者群体而言, 这种复杂的诊断和治疗策略使无事件生存期达到了34%。为明确大剂量化疗在晚期尤因肉瘤患者中的疗效，需要一种标准化的治疗策略，以便积累足够数量的患者进行该领域的大型合作研究。
