Younger lymphoma patients may be less susceptible to chemo-induced ovarian toxicity
Chemotherapy may be less damaging to fertility of female lymphoma patients who are of a younger age than those who are older, even in the case of an alkylating regimen, suggests a study presented at ESHRE 2018.
The monocentric observational study prospectively recruited 122 patients (aged 15–35 years) with non-Hogkin or Hogkin lymphoma before chemotherapy initiation. Based on their chemotherapy regimen, patients were categorized as being treated by either a non-alkylating (n=67) or an alkylating protocol (n=55). [ESHRE 2018, abstract P-516]
Fertility status was monitored through variations in levels of anti-Müllerian hormone (AMH), an indicator of the depletion and recovery of growing follicle in women treated by chemotherapy. Longitudinal variations of AMH may reflect ovarian toxicity of a chemotherapy regimen, and participants were measured on AMH levels at baseline (AMH0), 15 days after starting chemotherapy (AMH1), 15 days before the final cycle (AMH2), and at every 3-month interval for 24 months following the end of chemotherapy.
In general, ovarian recovery was complete and fast in patients treated with non-alkylating regimen while none of the patients who received alkylating regimen recovered to their initial pretreatment AMH value.
When the analyses were stratified by age group, ovarian recovery was fast and complete following non-alkylating treatment but progressive and partial with alkylating treatment in adolescent and young adult (AYA) patients (defined as age group 15–24 years).
Although serum AMH levels at all time points after a non-alkylating protocol were different from baseline, only AMH+12 and AMH+24 were significantly different when compared with AMH2 (p<0.0001).
Among non-AYA patients (aged 25–35 years), AMH levels also recovered more progressively in the non-alkylating group than the alkylating group; although the recovery was overall slower when compared with AYA patients on non-alkylating regimen.
After an alkylating regimen, serum AMH levels in non-AYA patients remained low and did not rise to levels that are statistically different from AMH2.
The detrimental effects of an alkylating protocol on fertility were observed not only in non-AYA patients, but also in AYA patients, whereby both groups never recovered their AMH levels to those prior to treatment — unlike patients treated with a non-alkylating regimen. Nonetheless, AYA patients on alkylating regimen still showed AMH levels that were higher than their non-AYA counterparts during the recovery phase.
“These results allow for the first time the development of evidence-based strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients,” said lead author Dr J. Bertrand-Delepine from Hopital Jeanne de Flandre in Lille, France.
Previously, age, chemotherapy type, and pretreatment AMH levels have been shown to predict ovarian recovery, but the findings were mainly demonstrated in breast cancer patients who were older than subjects in the current study.
Nonetheless, the researchers cautioned that the disparity in chemotherapy protocols among different groups, in particular the longer chemotherapy duration with alkylating protocol vs non-alkylating protocol, should be noted as a limitation.