Parenthood in Long-Term Survivors After CHOEP Treatment for Aggressive Lymphoma Is Not Significantly Impaired in Comparison to the General Population. Results From the Mabthera International Trial (MInT) and the DSHNHL NHLB1 Study

A growing number of patients with aggressive lymphoma experience long term survival after front-line treatment and survivorship issues have been increasingly addressed in recent years. Within treatment-induced sequelae, gonadal failure represents a major late-effect of chemotherapy. With respect to hematologic malignancies the majority of data on fertility effects pertains to Hodgkin Lymphoma treatment regimens whereas information on gonadal toxicity of non-Hodgkin Lymphoma treatments is limited. While CHOP as the standard treatment for aggressive lymphoma is supposed to be associated with only temporary side-effects on fertility in both sexes, nothing is known about the fertility effect of a moderate intensification of CHOP by adding etoposide in frequently used regimens such as CHOEP or dose-adjusted EPOCH.

Our study assessed fertility aspects in young patients with aggressive lymphoma who enjoy ongoing first remission after treatment in the Mabthera International Trial or the German DSHNHL NHLB1 study between 1995 and 2003. Long term survivors of both prospective studies were contacted and invited to answer a questionnaire. Patients who received radiotherapy to the gonadal area as part of their primary treatment as well as those who received chemotherapy for secondary neoplasia were excluded from the analysis. Data on parenthood obtained in the subgroup of patients who received 6 complete cycles (R)-CHOEP (total cyclophosphamide and etoposide dose 4,500 mg/m² and 1,800 mg/m², respectively) is reported here.

Altogether 66 (31 female, 35 male) patients agreed to participate in the survey. Median age at treatment was 32.5 years (range: 18 – 40) and at time of data collection 44 years (range: 28 – 55), respectively, with a median follow-up after treatment completion of 11 years (range: 7 – 17). While 31 (46.9%) patients already had children before treatment (18 female – 58.1%, 13 male – 37.1%), 35 (53.0%) expressed a clear desire for children after treatment (14 female – 45.2%, 21 male – 60.0%). Ten of these 35 patients did not try to achieve pregnancy, with lack of partner being the main reason. Of the remaining 25 patients (12 female, 13 male) who tried to achieve pregnancy, 18 (9 female – 75%, 9 male – 69%) were finally successful. Apart from 2 deliberate abortions all pregnancies were uncomplicated and resulted in 25 live births. No major health problems were reported in the children. The interval between completion of treatment and birth of first child after treatment ranged from 21 to 146 months (median 58 months) in female patients and from 25 months to 106 months (median 60.5 months) in male patients. Patients not achieving pregnancy tended to be older then patients who successfully achieved pregnancy (median age 30 versus 25 in female patients and 34.5 versus 28 years in male patients). Not achieving parenthood after treatment was associated with emotional stress in 3 of 3 female patients but only in 1 of 4 male patients. Fourteen patients chose cryopreservation of sperm before treatment but none of them utilized preserved sperm for reproductive purposes. Cryopreservation techniques were not used in female patients. Only one female patient received a GnRH analogue in parallel to chemotherapy and gave birth to two children after treatment.

Comparison of the presented patient data with the German general population (The German Socio-Economic Panel, 2011) revealed only non-significant differences in the overall percentage of childless women (16.1% in the study population versus 26.0% in the general population, p=0.15) and men (45.7% versus 33.8%, p=0.07). Total fertility rate in female study patients (1.45) paralleled that in the general population (around 1.4 between 1980 and 2010).

Parenthood after treatment with CHOP plus etoposide seems not to be significantly impaired in comparison to the general population. Most patients who had attempted post-treatment parenthood were successful. The small percentage of patients not achieving pregnancy despite a clear desire for parenthood after treatment is in line with previous reports on the fertility effects of CHOP. However, all patients of reproductive age should be offered counselling with regard to the impact of planned therapy on their fertility.

No relevant conflicts of interest to declare.