Challenges and Unmet Oncofertility Needs in Hematopoietic Stem Transplant Recipients in a Middle-Income Nation

Abstract

Lack of fertility assessment (FA) and counsel (FC) has a negative impact on quality of life in cancer survivors. Cryopreservation (CP) offers a possibility of future progeny in both males and females. Hematopoietic stem cell transplant (HSCT) recipients are a high-risk group, whose increased risk of relapse limits time off of therapy for CP. Our aim was to evaluate trends in pre and post-HSCT gonadal dysfunction (GD) in HSCT recipients in a referral center in Latin America.This is a retrospective single-center study that included patients who underwent HSCT at our institution from June 2000 to May 2018, whose baseline diagnosis was established at <45 years of age.Inclusion criteria were met by 213 patients. Median age at diagnosis was 26 years and 64.8% were male. 70.4% were of low socioeconomic (SE) status (monthly income <180 USD). Baseline diagnosis was hematologic in 84%. In 81.2% of patients, systemic cytotoxic therapy was required, with a median time to initiation of one day. Gonadal toxicity risk profile (GTP) of therapy was intermediate/high in 26.6% (Figure 1).Median age at HSCT was 29 years. HSCT was autologous in 54.9%. Median time from diagnosis to HSCT was 15 months and was 3 months from last therapy to HSCT. Conditioning regimen was myeloablative (MA) in 87.1% (Figure 1).Full pre-HSCT biochemical FA was available in 71.8% of patients (n=153) being consistent with GD in 22.9% (n=35). Female gender was associated with pre-HSCT GD (p<0.001), despite males receiving regimens of higher GTP (p<0.001). FC was performed in 55.4% (n=118) of patients, more so in women than men (p<0.001). Only 3.3% (n=7) of the cohort completed CP (Figure 2).At 6 months post-HSCT 193 patients were evaluable. Only 47.7% (n=92) had full FA. GD was present in 47.8% (n=44) and was related to female gender (p=0.03). Within females increased median concentration of FSH (p<0.001) and LH (p<0.001), lower median concentration of estradiol (p=0.005), and an association of GD with MA regimens (p=0.002) were observed. In males only FSH median concentration (p=0.002) was altered and GD was related to germ cell tumor (GCT) diagnosis (p=0.019) (Figure 2/3).Despite the young age of our cohort few patients received FC. CP was almost null due to SE constrains, accessibility, and limited therapy-free time. Only 1 of every 4 patients had biochemical evidence suggestive of GD pre-HSCT. Greater care must be taken to allocate intervals for CP while weighing risk of relapse.Factors related to GD were female gender, MA regimens in females, and GCT in males; possibly evidencing the role of the blood-testis barrier in decreasing intragonadal drug concentrations.The reduced proportion of post-HSCT FA evidences lack of awareness among clinicians.Our results show the great need of multidisciplinary approaches in HSCT recipients and resource-stratified guidelines to select those with the greatest potential to benefit from a fertility perspective. Lack of fertility assessment (FA) and counsel (FC) has a negative impact on quality of life in cancer survivors. Cryopreservation (CP) offers a possibility of future progeny in both males and females. Hematopoietic stem cell transplant (HSCT) recipients are a high-risk group, whose increased risk of relapse limits time off of therapy for CP. Our aim was to evaluate trends in pre and post-HSCT gonadal dysfunction (GD) in HSCT recipients in a referral center in Latin America. This is a retrospective single-center study that included patients who underwent HSCT at our institution from June 2000 to May 2018, whose baseline diagnosis was established at <45 years of age. Inclusion criteria were met by 213 patients. Median age at diagnosis was 26 years and 64.8% were male. 70.4% were of low socioeconomic (SE) status (monthly income <180 USD). Baseline diagnosis was hematologic in 84%. In 81.2% of patients, systemic cytotoxic therapy was required, with a median time to initiation of one day. Gonadal toxicity risk profile (GTP) of therapy was intermediate/high in 26.6% (Figure 1). Median age at HSCT was 29 years. HSCT was autologous in 54.9%. Median time from diagnosis to HSCT was 15 months and was 3 months from last therapy to HSCT. Conditioning regimen was myeloablative (MA) in 87.1% (Figure 1). Full pre-HSCT biochemical FA was available in 71.8% of patients (n=153) being consistent with GD in 22.9% (n=35). Female gender was associated with pre-HSCT GD (p<0.001), despite males receiving regimens of higher GTP (p<0.001). FC was performed in 55.4% (n=118) of patients, more so in women than men (p<0.001). Only 3.3% (n=7) of the cohort completed CP (Figure 2). At 6 months post-HSCT 193 patients were evaluable. Only 47.7% (n=92) had full FA. GD was present in 47.8% (n=44) and was related to female gender (p=0.03). Within females increased median concentration of FSH (p<0.001) and LH (p<0.001), lower median concentration of estradiol (p=0.005), and an association of GD with MA regimens (p=0.002) were observed. In males only FSH median concentration (p=0.002) was altered and GD was related to germ cell tumor (GCT) diagnosis (p=0.019) (Figure 2/3). Despite the young age of our cohort few patients received FC. CP was almost null due to SE constrains, accessibility, and limited therapy-free time. Only 1 of every 4 patients had biochemical evidence suggestive of GD pre-HSCT. Greater care must be taken to allocate intervals for CP while weighing risk of relapse. Factors related to GD were female gender, MA regimens in females, and GCT in males; possibly evidencing the role of the blood-testis barrier in decreasing intragonadal drug concentrations. The reduced proportion of post-HSCT FA evidences lack of awareness among clinicians. Our results show the great need of multidisciplinary approaches in HSCT recipients and resource-stratified guidelines to select those with the greatest potential to benefit from a fertility perspective. Figures 1, Figure 2, Figure 3.Figure 2Fertility & Gonadal Dysfunction Evaluation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Factors affecting gonadal dysfunction.View Large Image Figure ViewerDownload Hi-res image Download (PPT)