Fertility status among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: results of the 58 Late Adverse Effects study

Abstract

STUDY QUESTION What are the fertility outcomes of male and female childhood acute lymphoblastic leukaemia (ALL) long-term survivors? SUMMARY ANSWER We observed similar fertility outcomes in both male and female childhood ALL survivors compared with the general population, with the exception of a higher proportion of miscarriages among partners of male survivors. WHAT IS KNOWN ALREADY Survival after childhood ALL is currently >90% and fertility impairments are among the main concerns of the long-term survivors. Few studies have focused on the fertility issues within this selected population and the existing data are difficult to interpret due to the different treatment regimens received by the patients, the small sample sizes and the unavailability of control data in many studies. STUDY DESIGN, SIZE, DURATION Childhood ALL patients enrolled in European Organisation for Research and Treatment of Cancer (EORTC) studies between 1971 and 1998 in France and Belgium, <18 years old at diagnosis and alive and ≥18 years at follow-up were eligible. Among 1418 eligible survivors, 507 (35.8%) participated (277 females, 230 males). Controls from the general population matched one to one by age, province, level of urbanization and sex could be identified for 503 survivors. PARTICIPANTS/MATERIALS, SETTING, METHODS Survivors and controls were invited to fill out a questionnaire including information about their menstrual cycles (for females), intention to have children, having children, use of medical help to become pregnant and occurrence of negative pregnancy outcomes (birth defect, miscarriage, medical abortion or stillbirth). The results were analysed separately for females and males. The association between age at diagnosis and fertility outcomes, adjusted by age at follow-up, study and country were investigated using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE The median time since diagnosis was 20.1 years and the median age at follow-up was 25 years. There were 144 survivors (97 females, 47 males) who wanted to have children. Among these, craniospinal radiotheraphy (CRT) and haematopoietic stem cell transplantation (HSCT) were administered to 18% and 4%, respectively. Of these who tried to have children, 75% of females and 69% of males succeeded, compared with 72% and 61% of the controls, respectively. These differences were not statistically significant (P = 0.73 for females and P = 0.50 for males). Overall, fertility outcomes were comparable between survivors and controls, except that a higher proportion of miscarriages occurred in partners of male survivors (28.1% versus 5.9%, P = 0.021). Among female survivors, an older age at diagnosis (10–17 years) was associated with a greater risk of pregnancy problems (adjusted OR 5.61, P = 0.046). LIMITATIONS, REASONS FOR CAUTION The interpretation of the incidence of miscarriage among the partners of male survivors is limited by the lack of data regarding the males’ partners and by a possibly higher tendency to recall and disclose fertility issues among male survivors compared with male controls. WIDER IMPLICATIONS OF THE FINDINGS Fertility outcomes were similar in childhood ALL survivors and controls, and the low proportion of patients treated with CRT or HSCT might explain this. Further studies should confirm the higher proportion of miscarriages in partners of male survivors. STUDY FUNDING/COMPETING INTEREST(S) This publication was supported by donations from the Fonds Cancer (FOCA) from Belgium and the KU Leuven from Belgium. G.R. has been awarded a fellowship by the EORTC Cancer Research Fund (ECRF). C.P. has been awarded a fellowship by Fonds Cancer (FOCA) from Belgium and the Kinderkankerfonds from Belgium (a non-profit childhood cancer foundation under Belgian law). No competing interests were declared. TRIAL REGISTRATION NUMBER NCT01298388 (clinicaltrials.gov).

Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies

“…A total of 1418 childhood ALL survivors were eligible in the 58LAE project, among whom 507 answered to the socio-economic questionnaire and were eligible for the QoL evaluation (see earlier publication [ 30 ]). Among them, 183 responded (36.1%) and 3 additional patients provided QoL data but no socio-economic data, leading to a total of 186 respondents (109 females and 77 males).…”

“…Adult survivors (≥18 years) who were diagnosed with ALL during childhood (<18 years at diagnosis) and registered in the European Organisation for Research and Treatment of Cancer (EORTC) Children Leukaemia Group (CLG) trials 58741 (1971–1978), 58831/2 (1983–1989) and 58881 (1989–1998) were eligible. Details regarding the risk-group stratification and the treatment protocols were described earlier [ 30 , 31 ] and provided in Figure S1 . Follow-up data, including QoL data, were collected from 24 institutions (10 in Belgium and 14 in France).…”

Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies

“…In this section, we provide details on definitions (i.e., CNS involvement), treatments (i.e., CRT, hematopoietic stem cell transplantation [HSCT] and high-dose cytarabine [HD Cytarabine]) and risk group (very high-risk [VHR] in study 58881) considered for the study of association with neurotoxicity (Table 1 ). Other details regarding studies 58741, 58831/2 and 58881 are reported in Supplementary Table S1) [ 15 ].…”

Methods for preserving fertility in childhood cancer patients

“…Как противоопухолевая терапия, так и основное заболевание пациента могут привести к репродуктивной дисфункции и в дальнейшем к бесплодию. Противоопухолевое лечение может иметь как немедленные, так и отсроченные неблагоприятные последствия для репродуктивного здоровья [3]. По данным научных исследований, у взрослых пациентов, перенесших краниальную лучевую терапию и химиотерапию в связи с лечением лейкоза в детском возрасте, выявлены значительные нарушения фертильности и снижение частоты наступления беременности [4,5].…”