Effects of treatments on gonadal function in long‐term survivors of pediatric hematologic malignancies: A cohort study

Abstract

Background: Potentially gonadotoxic protocols are currently used for the treatment of childhood hematologic malignancies. This study aims to evaluate the prevalence of gonadal dysfunction and the most important associated risk factors in a cohort of hematologic malignancy survivors. Procedure: We considered all patients referred to our long-term follow-up clinic for childhood cancer survivors, between November 2001 and December 2017. Inclusion criteria were: (a) previous diagnosis of hematologic malignancy; (b) age at hematologic malignancy diagnosis < 18 years; (c) at least five years after the end of anticancer treatments; (d) at least one evaluation of gonadal function after the 18th birthday. Patients diagnosed before January 1, 1990, were excluded. Results: Three hundred twenty-seven survivors (males = 196) were included. Isolated spermatogenesis damage was found in 58/196 (29.6%) of males, whereas 18/196 (9.2%) had Leydig cell failure. In females, 35/131 (26.7%) experienced premature ovarian insufficiency. In both sexes, abdominopelvic irradiation and hematopoietic stem cell transplantation were strongly associated with the risk of gonadal dysfunction. For every 1000 mg/m 2 increase in cyclophosphamide-equivalent dose exposure, the risk of spermatogenesis damage increased 1.52-fold and that of Leydig cell failure increased 1.34-fold, whereas the risk of premature ovarian insufficiency increased 1.80-fold. About 30% of those males who developed Leydig cell failure did so more than five years after the end of treatments. Conclusions: Gonadal dysfunction is still a significant late effect of therapies for pediatric hematologic malignancies. In males, the reevaluation of Leydig cell function may be useful even several years after the exposure to gonadotoxic treatments.

Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma: a review

“…The number of female survivors with POI was reported in seven of the included studies (1516 patients) ( Table II and Supplementary Fig. S1 ) ( Green et al , 1981 ; Sklar et al , 2006 ; Zaletel et al , 2010 ; van der Kaaij et al , 2012b ; Swerdlow et al , 2014 ; Levine et al , 2018 ; Felicetti et al , 2020 ). The percentage of female HL survivors with signs of POI ranged from 6% to 34% (median 9%) and was especially high in patients receiving radiotherapy and BEAM (i.e.…”

“…Among the eligible studies, the reported percentage of patients with elevated FSH ranged from 0% to 100% (median 51.5%). Nine studies used the generally accepted cutoff value of 10 IU/L to determine high FSH serum level, indicating damage to spermatogenesis ( Sherins et al , 1978 ; Hassel et al , 1991 ; Heikens et al , 1996 ; Mackie et al , 1996 ; Müller et al ., 1996 ; van den Berg et al , 2004 ; Servitzoglou et al ., 2015 ; Brignardello et al , 2016 ; Felicetti et al , 2020 ). The other studies used higher cutoff values (i.e.…”

In vitro maturation of immature oocytes for fertility preservation in cancer patients compared to control patients with fertility problems in an in vitro fertilization program

“… 2 In long-term female survivors of pediatric hema tologic malignancies 26.7% experienced premature ovarian insufficiency and face infertility after cancer treatment. 3 The situation is similar with other cancers; cancer therapy is the cause of premature ovarian failure in 25% of women with this diagnosis. 4 Therefore, it is very important to consider the preservation of female fertility before oncotherapy.…”

Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation

“…Infertility is another well-recognized side effect of HSCT [ 69 , 70 , 71 , 72 ], since the seminiferous tubules in males and the ovaries in females are highly sensitive to the detrimental effects of alkylating agents and RT [ 73 , 74 , 75 ]. Patients exposed to TBI show a significant risk of cataracts [ 76 ] and of skeletal alteration [ 77 ], involving also dental and/or craniofacial skeletal structures, with a clear relation to the age at treatment [ 78 ].…”