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霍奇金淋巴瘤或非霍奇金淋巴瘤及其治疗对精子非整倍体的影响:法国CECOS网络的一项前瞻性研究。

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network.

作者信息

Martinez Guillaume, Walschaerts Marie, Le Mitouard Marine, Borye Remi, Thomas Claire, Auger Jacques, Berthaut Isabelle, Brugnon Florence, Daudin Myriam, Moinard Nathalie, Ravel Célia, Saias Jacqueline, Szerman Ethel, Rives Nathalie, Hennebicq Sylviane, Bujan Louis

机构信息

Université Grenoble-Alpes, Institut National de la Santé et de la recherche Médicale (INSERM) U-1029, Grenoble, France; Laboratoire d'Aide à la Procréation-CECOS, Centre Hospitalier Universitaire (CHU) de Grenoble, Grenoble, France.

Université de Toulouse III; Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France.

出版信息

Fertil Steril. 2017 Feb;107(2):341-350.e5. doi: 10.1016/j.fertnstert.2016.10.001. Epub 2016 Oct 31.

Abstract

OBJECTIVE

To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments.

DESIGN

Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months.

SETTING

University hospitals.

PATIENT(S): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied.

INTERVENTION(S): Semen analyses and aneuploidy study by FISH were performed at each time point.

MAIN OUTCOME MEASURE(S): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment.

RESULT(S): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment.

CONCLUSION(S): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

摘要

目的

评估霍奇金淋巴瘤(HL)和非霍奇金淋巴瘤(NHL)患者治疗前后的精子生成及非整倍体情况。

设计

对淋巴瘤患者进行多中心、前瞻性纵向研究,在治疗前及治疗后3、6、12和24个月进行分析。

地点

大学医院。

患者

45例HL患者和13例NHL患者在治疗前后接受了调查。治疗方案分为两组:含或不含(±)放疗的阿霉素、博来霉素、长春花碱、达卡巴嗪(ABVD)方案,以及环磷酰胺、阿霉素、长春新碱、泼尼松(CHOP)/氮芥、长春新碱、丙卡巴肼、泼尼松 - 阿霉素、博来霉素、长春花碱(MOPP - ABV)方案。还对29名健康男性组成的对照组进行了研究。

干预措施

在每个时间点进行精液分析和荧光原位杂交(FISH)非整倍体研究。

主要观察指标

比较治疗前后精子的平均特征及精子非整倍体率的百分比。

结果

治疗前,HL和NHL男性的精液特征改变,精子非整倍体率(中位数0.76[四分位间距0.56 - 0.64])高于对照组(0.54[0.46 - 0.74])。治疗后,接受ABVD±放疗或CHOP/MOPP - ABV治疗后3个月和6个月精子生成显著降低。接受ABVD±放疗后,仅在3个月时非整倍体率显著升高,1年或2年后获得的值低于治疗前值。相比之下,在CHOP/MOPP - ABV治疗组中,精液特征和非整倍体率直到治疗后2年才恢复到正常水平。

结论

淋巴瘤本身在治疗前对精子非整倍体频率有影响。此外,淋巴瘤治疗对精子染色体有有害影响,这与治疗类型及治疗后的时间有关。关于淋巴瘤及其治疗引起的短暂但显著的精子非整倍体情况,对患者进行咨询至关重要。

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