美国西雅图儿童医院Julie R. Park小组探讨了串联自体干细胞移植与单次移植对高危神经母细胞瘤患者无事件生存率的影响。 这一研究成果发表在2019年8月27日出版的国际学术期刊《美国医学会杂志》上。

2007年11月至2012年2月，美国、加拿大、瑞士、澳大利亚和新西兰的142个儿童肿瘤组中心对652名30岁及以下的高危神经母细胞瘤患者进行了一项随机临床试验。其中297名患者没有进行随机分组。在355名随机分组的患者中，平均年龄为36.1个月，女性占42.8%，随机接受串联移植联合噻替帕/环磷酰胺随后给予减量的卡铂/依托泊苷/美法仑（176例）或单次移植联合卡铂/依托泊苷/美法仑（179例），最终297名患者（83.7%）完成研究，21名患者（5.9%）在治疗后失访。

随机分组后，串联移植组的3年无事件生存率为61.6%，单次移植组为48.4%，差异具有统计学意义。181例无事件患者的中位随访持续时间为5.6年。移植后最常见的毒副作用为粘膜毒性和传染性，串联移植组中两者的发生率分别为11.7%和17.9%，单次移植组分别为15.4%和18.3%。

在30岁及以下的高危神经母细胞瘤患者中，串联移植的无事件生存率显著优于单次移植。 然而，由于随机化率较低，该研究结果可能并不适用所有高危神经母细胞瘤患者。

研究人员表示，高剂量化疗联合自体干细胞移植以及随后的抗神经节苷脂抗体免疫治疗，是高危神经母细胞瘤患者的标准治疗方案，但患者生存率仍较低。

附：英文原文

Title: Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma

Author: Julie R. Park, Susan G. Kreissman, Wendy B. London, Arlene Naranjo, Susan Lerner Cohn, Michael D. Hogarty, Sheena C. Tenney, Daphne Haas-Kogan, Peter John Shaw, Jacqueline M. Kraveka, Stephen S. Roberts, James Duncan Geiger, John J. Doski, Stephan D. Voss, MD, John M. Maris, Stephan A. Grupp, Lisa Diller

Issue&Volume: August 27, 2019, Vol 322, No. 8

Abstract:

Importance  Induction chemotherapy followed by high-dose therapy with autologous stem cell transplant and subsequent antidisialoganglioside antibody immunotherapy is standard of care for patients with high-risk neuroblastoma, but survival rate among these patients remains low.

Objective  To determine if tandem autologous transplant improves event-free survival (EFS) compared with single transplant.

Design, Setting, and Participants  Patients were enrolled in this randomized clinical trial from November 2007 to February 2012 at 142 Children’s Oncology Group centers in the United States, Canada, Switzerland, Australia, and New Zealand. A total of 652 eligible patients aged 30 years or younger with protocol-defined high-risk neuroblastoma were enrolled and 355 were randomized. The final date of follow-up was June 29, 2017, and the data analyses cut-off date was June 30, 2017.

Interventions  Patients were randomized to receive tandem transplant with thiotepa/cyclophosphamide followed by dose-reduced carboplatin/etoposide/melphalan (n = 176) or single transplant with carboplatin/etoposide/melphalan (n = 179).

Main Outcomes and Measures  The primary outcome was EFS from randomization to the occurrence of the first event (relapse, progression, secondary malignancy, or death from any cause). The study was designed to test the 1-sided hypothesis of superiority of tandem transplant compared with single transplant.

Results  Among the 652 eligible patients enrolled, 297 did not undergo randomization because they were nonrandomly assigned (n = 27), ineligible for randomization (n = 62), had no therapy (n = 1), or because of physician/parent preference (n = 207). Among 355 patients randomized (median diagnosis age, 36.1 months; 152 [42.8%] female), 297 patients (83.7%) completed the study and 21 (5.9%) were lost to follow-up after completing protocol therapy. Three-year EFS from the time of randomization was 61.6% (95% CI, 54.3%-68.9%) in the tandem transplant group and 48.4% (95% CI, 41.0%-55.7%) in the single transplant group (1-sided log-rank P=.006). The median (range) duration of follow-up after randomization for 181 patients without an event was 5.6 (0.6-8.9) years. The most common significant toxicities following tandem vs single transplant were mucosal (11.7% vs 15.4%) and infectious (17.9% vs 18.3%).

Conclusions and Relevance  Among patients aged 30 years or younger with high-risk neuroblastoma, tandem transplant resulted in a significantly better EFS than single transplant. However, because of the low randomization rate, the findings may not be representative of all patients with high-risk neuroblastoma.

DOI: 10.1001/jama.2019.11642

Source: https://jamanetwork.com/journals/jama/article-abstract/2748795