Background

Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database.

Methods

We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995–2004, and 2005–18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997.

Findings

Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4–91·1) for 62 pregnant patients and 88·3% (81·6–92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84–3·87; p=0·130; 5-year overall survival was 97·3% (82·3–99·6) and 98·4% (93·6–99·6; HR 1·63, 0·35–7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8–98·7) versus 74·0% (60·9–83·3); HR 0·36, 95% CI 0·04–2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5–99·1; HR cannot be estimated; p=0·146).

Interpretation

Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth.

Funding

European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.

中文翻译：

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妊娠期间诊断为霍奇金淋巴瘤的患者的产科和产妇预后：一项多中心，回顾性队列研究

背景

妊娠期间诊断为霍奇金淋巴瘤后母亲和儿童的结局调查不足，尚未广泛报道对该病的产前管理。这项研究的目的是评估在国际癌症，不育和怀孕网络（INCIP）数据库中注册的，在妊娠期间诊断出的霍奇金淋巴瘤患者的产科结局，产前管理和孕产妇存活率。

方法

我们进行了一项多中心，回顾性队列研究，包括1969年1月1日至2018年8月1日之间134位诊断为霍奇金淋巴瘤的孕妇的肿瘤和产科数据。从INCIP数据库收集的数据来自比利时，捷克共和国的17个学术中心，丹麦，希腊，以色列，意大利，墨西哥，荷兰，俄罗斯，英国和美国。我们分析了三个时期（1995年之前，1995–2004年和2005-18年之前）的患者管理。将接受产前化疗的患者的产科结局（出生体重，产科或新生儿并发症以及进入新生儿重症监护病房[NICU]）与未接受产前治疗的患者进行比较。通过对孕妇进行诊断时的疾病分期来评估孕产妇的无进展生存期和总生存期，并将其与从三个三级中心的数据库中选择的霍奇金淋巴瘤的非妊娠患者的结局进行比较，并根据分期和预后评分进行匹配。自1997年1月1日以来，所有纳入生存分析的患者均接受标准的阿霉素，博来霉素，长春碱和达卡巴宗（ABVD）治疗。

发现

在怀孕期间被诊断出霍奇金淋巴瘤的134名孕妇中。72例（54％）患者开始了产前化疗，56例（42％）在怀孕期间未接受治疗，6例（4％）仅接受了放射治疗。多年来，在怀孕期间越来越多地开始化学疗法。在接受化学疗法的新生儿（69名中的15 [22％]）和未接受化学疗法的新生儿（42中的6 [16％]； p = 0·455）之间，胎龄小的新生儿的发生率没有差异。两组之间NICU的入院率也没有差异（19 [29％]接受过产前化疗与12 [35％]未接受过产前化疗）。与未暴露的新生儿相比，出生前接受化疗的新生儿的出生体重百分比更低（p = 0·035）。接受产前治疗的患者的产科并发症要比没有接受产前治疗的患者多（p = 0·005），最常见的并发症是早产（9例[12％] vs 3例[7％]）和胎膜早破（4例[5]） ％]与0）。对于孕产妇生存分析，我们比较了77名孕妇和211名未怀孕，匹配的对照。早期霍奇金淋巴瘤患者的5年无进展生存率分别为62例妊娠患者和82·3％（81·6–92·7）的82·6％（95％CI 67·4–91·1）。 142位对照者（危险比[HR] 1·80，95％CI 0·84-3·87； p = 0·130； 5年总生存率为97·3％（82·3-99·6）， 98·4％（93·6-99·6; HR 1·63，0·35-7·65; p = 0·534）。患有晚期疾病的患者（15例孕妇和69例非孕妇对照） ），五年无进展生存率分别为90·9％（95％CI 50·8–98·7）和74·0％（60·9–83·3）； HR 0·36，95％CI 0 ·04-2·90； p = 0·334。5年总生存率为100％（无事件发生）和96·2％（95％CI 85·5-99·1；无法估计HR； p = 0·146）。

解释

与接受妊娠前未开始治疗的霍奇金淋巴瘤患者相比，接受产前治疗的患者发生早产收缩或胎膜早破的可能性更高。霍奇金淋巴瘤的孕妇和非孕妇的孕产妇生存率无差异，这表明某些患者可以考虑进行产前化疗或推迟至产后治疗，并定期进行产科随访以保障胎儿的生长。

资金

欧洲研究委员会，法兰德斯研究基金会和捷克共和国查尔斯大学卫生部。