Parenthood in long‐term survivors after CHOP with or without etoposide treatment for aggressive lymphoma

We read with great interest the report of Greaves et al (2013) regarding patient-perceived fertility and sexual function in long-term survivors of haematological malignancy. The authors describe a lower cumulative fertility rate in female patients than in the matched general population as well as a negative impact of cancer on sexual function. We agree with their conclusion that all patients should be advised of the potential late effects of treatment on fertility. However, as different treatment regimens are associated with varying degrees of gonadal toxicity, the patient should be informed of the risks that are related to the specific regimen (Loren et al, 2013). To complement the report of Greaves et al (2013), we would like to share our results of a retrospective analysis on the side effects on fertility in patients with aggressive non-Hodgkin lymphoma (NHL) who received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone) as primary therapy. Only a few studies have been performed on the adverse effects of chemotherapy for aggressive NHL on fertility (Grigg, 2004; Leader et al, 2011), most of which included small numbers of patients, employed heterogeneous chemotherapy regimens or covered short follow-up periods. Whereas CHOP as a standard regimen for aggressive lymphoma is supposed to be associated with only temporary side-effects on fertility, nothing is known about the effect of intensification of CHOP, e.g. by adding etoposide in regimens such as CHOEP (Pfreundschuh et al, 2004) or dose-adjusted EPOCH (Wilson et al, 2002), or of dose-dense chemotherapy. Our study assessed fertility aspects in young patients who were in continuous first remission after treatment in two large prospective multicentre trials, the Mabthera International Trial (Pfreundschuh et al, 2006), and the German High-Grade Non-Hodgkin’s Lymphoma Study Group NHLB1 study (Pfreundschuh et al, 2004), between 1995 and 2003. We focused on parenthood to assess fertility in our patient group, as infertility is defined as the inability of a couple to conceive. Surrogate indicators, such as regular menstruation cycles or hormone levels alone could provide only incomplete information. Long-term survivors of both studies were invited to respond to a questionnaire approved by the local ethics committee. Informed consent was obtained from all responders. Patients who received radiotherapy to the gonadal area as part of their primary treatment were excluded from the analysis. A total of 101 patients (median age at treatment initiation 32 years, median follow-up after treatment completion 12 years) agreed to participate in the survey [response rate of 53 1%; comparable to the report of Greaves et al (2013)]. Within the respondents (46 female, 55 male), 48 patients already had children before lymphoma treatment (Table I). Forty-nine patients expressed an explicit wish to have children after treatment (17 female, 32 male). Thirteen of these 49 patients made no active attempt to reproduce despite their wish to have children, with lack of appropriate partner (six patients) and fear of lymphoma relapse (three patients) being the main reasons. Of the remaining 36 patients (13 female, 23 male) who made active attempts to reproduce, 26 (10 female, 16 male) achieved their goals, all without use of assisted reproduction technology. Apart from three deliberate abortions, all pregnancies were uncomplicated and resulted in a total of 40 live births. The results in the subgroup of patients who received CHOEP instead of CHOP were similar to those in the whole study group. In detail, 36 (15 female, 21 male) of 67 (32 female, 35 male) patients treated with CHOEP expressed a wish to reproduce after chemotherapy. Of these, 25 (12 female, 13 male) actively attempted to reproduce and 19 (10 female, nine male) finally succeeded, resulting in 25 live births overall. Within the subgroup of patients who were treated with a 2-week regimen, three of three female and six of eight male patients with a desire for parenthood were successful. Comparison of patient data with the German general population [The German Socio-Economic Panel Study (Schmitt, 2005)] revealed no difference in the overall percentage of childless women (21 7%) in the study population versus comparable age-groups of the general population [20 8%, binomial test, 95% confidence interval (CI), 0 109–0 364; P = 0 8563]. The percentage of childless male study patients (41 8%) tended to be higher than that of childless men in the general population (32 6%). This statistically insignificant difference (95% CI, 0 287–0 559; P =