In young females with lymphoma, the impact of immunochemotherapy on fertility status has been poorly studied. Primary mediastinal B-cell lymphoma (PMBL) predominantly affects young females and is highly curable with the dose-adjusted EPOCH-rituximab (DA-EPOCH-R) regimen (Dunleavy et al., NEJM 2013:368;1408). We therefore identified this group of PMBL patients as an excellent population to study fertility status and evaluated the impact of DA-EPOCH-R on gonadal function of females aged 50 years or less.
A questionnaire was first mailed to 27 patients, and this was followed by a semi-structured phone interview to obtain information on patients' medical and gynecologic/obstetric histories before PMBL diagnosis, during treatment and after its completion. Serum estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were analyzed before commencing chemotherapy, following 5-6 cycles of DA-EPOCH-R, and 10-18 months after treatment completion.
All patients included in the study completed 6-8 cycles of DA-EPOCH-R and were in complete remission from PMBL at a median follow-up of 63 months. Median age at diagnosis was 30.5 years (r 21-50). Twenty-three patients participated in the questionnaire. Prior to chemotherapy, twenty of twenty-three were menstruating, three patients were not. Of the twenty menstruating patients treated with DA-EPOCH-R three were unsure of their menstrual histories during chemotherapy, fourteen (70%) developed amenorrhea and three (15%), all younger than 25 years, continued to menstruate. After completion of chemotherapy, fifteen of the twenty patients (75%) had menstrual periods. All were 35 years or younger. Five patients (25%) remained amenorrheic following completion of chemotherapy, however one had a hysterectomy shortly after treatment completion. To date six of twenty (30%) patients have conceived naturally and delivered healthy children with nine not yet desiring motherhood.
On laboratory evaluations performed before treatment, after 5-6 cycles of DA-EPOCH-R and 10-18 months after completion of chemotherapy, median serum LH levels were 2.5, 33.4 and 4.6 U/L respectively, median FSH values at the same time points were 3.6, 69.5 and 8 U/L, while median E2 levels were 24.4, <5 and 16.7 pg/mL, time courses consistent with transient ovarian damage from chemotherapy, but with recovery at a median follow-up of 12 months. Eight patients, who were 40 years or older were treated with DA-EPOCH-R. The median endocrine laboratory parameters of six of these patients, who had clinically normal ovarian function prior to treatment were examined at the indicated time points and were as follows: LH: 2.6, 36.4, 26.7 U/L; FSH: 6.4, 102.8, 83.9 U/L; E2: 68.8, <5, <5 pg/mL, a pattern consistent with premature menopause.
Fertility appears to be preserved in female PMBL patients receiving DA-EPOCH-R, particularly in those less than 40 years old. The risk of premature menopause seems to be confined to patients over 40 years of age. Further analysis of ovarian reserve in patient younger than 40 years, measuring Anti-Muellerian hormone and inhibin-B pre- and post-treatment, is ongoing.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.