Transplant and Nontransplant Salvage Therapy in Pediatric Relapsed or Refractory Hodgkin Lymphoma: The EuroNet-PHL-R1 Phase 3 Nonrandomized Clinical Trial.

Background

To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.

研究是否可以在再诱导化疗前后通过预挽救风险因素和氟脱氧葡萄糖-18（FDG）正电子发射断层扫描（PET）反应来指导高剂量化疗/自体干细胞移植（HDCT/aSCT）或无移植巩固治疗（放射治疗）的升级或降级，以最小化毒性效应，同时保持高治愈率。

DESIGN, SETTING, AND PARTICIPANTS: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013.

EuroNet-PHL-R1 是一项非随机临床试验，招募了 2007 年 1 月至 2013 年 1 月期间在欧洲 13 个国家的 68 个地点中年龄小于 18 岁的初发复发/难治性 cHL 患者。

Data were analyzed between September 2022 and July 2024.

数据在 2022 年 9 月至 2024 年 7 月期间进行了分析。

intervention

Reinduction chemotherapy consisted of alternating IEP (ifosfamide, etoposide, prednisolone) and ABVD (adriamycin, bleomycin, vinblastine, dacarbazine).

再诱导化疗包括交替使用IEP（异环磷酰胺、依托泊苷、泼尼松）和ABVD（阿霉素、博莱霉素、长春碱、达卡巴嗪）。

Patients with low-risk disease (late relapse after 2 cycles of first-line chemotherapy and any relapse with an adequate response after 1 IEP/ABVD defined as complete metabolic response on FDG-PET and at least 50% volume reduction) received a second IEP/ABVD cycle and radiotherapy (RT) to all sites involved at relapse.

低风险疾病患者（在首次化疗两个周期后晚期复发，以及在1个IEP/ABVD周期后任何复发且有充分反应，定义为FDG-PET上的完全代谢反应和至少50%的体积减少）接受了第二个IEP/ABVD周期和复发时涉及的所有部位的放射治疗（RT）。

Patients with high-risk disease (all primary progressions and relapses with inadequate response after 1 IEP/ABVD cycle) received a second IEP/ABVD cycle plus HDCT/aSCT with or without RT.

高风险疾病患者（所有一线治疗/ABVD方案一个周期后仍进展或复发且反应不足的患者）接受了第二轮IEP/ABVD治疗加上高剂量化疗/自体干细胞移植（HDCT/aSCT），可能伴有放疗（RT）。

main_outcomes_and_measures

The primary end point was 5-year event-free survival. Secondary end points were overall survival(OS) and progression-free survival(PFS).

主要终点是5年无事件生存率。次要终点包括总生存（OS）和无进展生存（PFS）。

PFS was identical to event-free survival because no secondary cancers were observed.

由于未观察到继发性癌症，无进展生存期（PFS）与无事件生存期相同。

PFS data alone are presented for simplicity.

为了简化，仅呈现了无进展生存期（PFS）数据。

Results

Of 118 patients analyzed, 58 (49.2%) were female, and the median (IQR) age was 16.3 (14.5-17.6) years.

在分析的118名患者中，58名（49.2%）为女性，中位年龄（四分位数间距）为16.3（14.5-17.6）岁。

The median (IQR) follow-up was 67.5 (58.5-77.0) months.

中位随访时间（四分位数间距）为67.5（58.5-77.0）个月。

The overall 5-year PFS was 71.3% (95% CI, 63.5%-80.1%), and OS was 82.7% (95% CI, 75.8%-90.1%).

五年总无进展生存期（PFS）为71.3%（95%置信区间，63.5%-80.1%），总生存（OS）为82.7%（95%置信区间，75.8%-90.1%）。

For patients in the low-risk group (n = 59), 41 received nontransplant salvage with a 5-year PFS of 89.7% (95% CI, 80.7%-99.8%) and OS of 97.4% (95% CI, 92.6%-100%).

低风险组患者（n = 59）中，41人接受了非移植挽救治疗，其五年无进展生存期（PFS）为89.7%（95%置信区间，80.7%-99.8%），总生存（OS）为97.4%（95%置信区间，92.6%-100%）。

In contrast, 18 received HDCT/aSCT off protocol, with a 5-year PFS of 88.9% (95% CI, 75.5%-100%) and OS of 100%.

相比之下，18名患者在非方案指导下接受了高剂量化疗/自体干细胞移植（HDCT/aSCT），5年无进展生存（PFS）为88.9%（95%置信区间，75.5%-100%），总生存（OS）为100%。

All 59 patients with high-risk disease received HDCT/aSCT (and 23 received post-HDCT/aSCT RT) with a 5-year PFS of 53.3% (95% CI, 41.8%-67.9%) and OS of 66.5% (95% CI, 54.9%-80.5%).

所有59名高风险疾病的患者均接受了高剂量化疗/自体干细胞移植（HDCT/aSCT）（其中23名患者接受了HDCT/aSCT后的放疗），5年无进展生存（PFS）为53.3%（95%置信区间，41.8%-67.9%），总生存（OS）为66.5%（95%置信区间，54.9%-80.5%）。

conclusion_and_relevance

In this nonrandomized clinical trial, FDG-PET response-guided salvage in relapsed cHL may identify patients in whom transplant-free salvage achieves excellent outcomes.

在这项非随机临床试验中，通过FDG-PET反应指导的复发性经典霍奇金淋巴瘤（cHL）的挽救治疗可能识别出那些无需移植即可获得极佳结果的患者。

HDCT/aSCT may be reserved for primary progression and relapsed cHL with inadequate response.

对于原发进展和对挽救治疗反应不足的复发性cHL患者，高剂量化疗联合自体干细胞移植（HDCT/aSCT）可能被保留作为治疗选择。

trial_registration

ClinicalTrials.gov Identifier: NCT00433459.

临床试验注册号：NCT00433459。