采用PET适应性方案治疗的晚期霍奇金淋巴瘤患者性腺功能恢复情况：一项随机III期试验（AHL2011）的前瞻性分析
Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011).
作者信息
Demeestere Isabelle, Racape Judith, Dechene Julie, Dupuis Jehan, Morschhauser Franck, De Wilde Virginie, Lazarovici Julien, Ghesquieres Hervé, Touati Mohamed, Sibon David, Alexis Magda, Gac Anne-Claire, Moatti Hannah, Virelizier Emmanuelle, Maisonneuve Hervé, Pranger Delphine, Houot Roch, Fornecker Luc-Matthieu, Tempescul Adrian, André Marc, Casasnovas René-Olivier
机构信息
Research Laboratory on Human Reproduction and Fertility Clinic, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Research Center in Epidemiology, Biostatistics and Clinical Research, School of Public Health, and Biomedical Research Department, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium.
出版信息
J Clin Oncol. 2021 Oct 10;39(29):3251-3260. doi: 10.1200/JCO.21.00068. Epub 2021 Jun 22.
PURPOSE
The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) in early responders on the basis of a positron emission tomography (PET)-driven strategy was safe and minimized toxicity compared with standard 6 BEACOPP cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old.
METHODS
Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up.
RESULTS
A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPP group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; = .004).
CONCLUSION
Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
目的
前瞻性随机AHL2011试验表明，对于基于正电子发射断层扫描（PET）驱动策略的早期缓解者，在接受两个周期的博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、丙卡巴肼和泼尼松（BEACOPP）方案治疗后，使用多柔比星、博来霉素、长春碱和达卡巴嗪方案（ABVD）是安全的，且与标准的6个周期BEACOPP相比，毒性最小。这项子研究调查了该策略对45岁以下患者性腺功能和生育能力的益处。
方法
通过检测女性血清中的促卵泡激素（FSH）、雌二醇和抗苗勒管激素来评估卵巢功能，通过精液分析、FSH和睾酮水平来评估男性在基线、治疗结束时以及5年随访期间的睾丸功能。
结果
共纳入了2011年5月19日至2014年4月29日期间入组的145名女性和424名男性。在PET驱动组中，治疗后卵巢早衰（FSH>24 IU/L）和卵巢储备功能低下（抗苗勒管激素<0.5 ng/mL）的风险降低（优势比[OR]分别为0.20；95%置信区间[CI]为0.08至0.50；P =.001和OR为0.15；95% CI为0.04至0.56，P =.005）。这两个参数均与年龄和烷化剂剂量相关。然而，在妊娠率方面未观察到显著差异。与标准BEACOPP组相比，PET驱动组的男性在治疗后精子参数的恢复率更高，严重睾丸损伤的风险更低（OR为0.26；95% CI为0.13至0.5；P<.0001），且实现妊娠的可能性更高（OR为3.7；95% CI为1.4至9.3；P =.004）。
结论
虽然两种治疗方法均影响卵巢储备和精子发生，但PET驱动策略降低了晚期霍奇金淋巴瘤患者性腺功能障碍和不孕的风险。
Zotero 插件