Potential gonadotoxicity of treatment in relation to quality of life and mental well-being of male survivors of childhood acute lymphoblastic leukemia

Gunn, Mirja Erika; Lähteenmäki, Päivi; Puukko-Viertomies, Leena-Riitta; Henriksson, Markus; Heikkinen, Risto; Jahnukainen, Kirsi

doi:10.1007/s11764-013-0285-7

Cited by 17 publications

(43 citation statements)

References 25 publications

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“…We previously reported a negative association between gonadotoxic ALL therapy, testicular irradiation and cyclophosphamide treatment, with FSH levels, testosterone levels, semen quality, fertility, and mental health in this patient cohort. 2,14 More specifically, men who had received testicular irradiation were sterile and needed testosterone substitution. 2 An important observation is that the late effects of gonadotoxic cancer therapy extend beyond fertility issues to the quality of orgasms and the perceived quality of sexual relations.…”

Section: Discussionmentioning

confidence: 99%

“…In total, 52 men (69%) agreed to participate in a larger study of male ALL survivors that assessed reproductive and bone health, related parameters, and overall well being at adult ages, as previously described. 2,13,14 The participants underwent a physical examination and an interview, provided blood and semen samples, and completed questionnaires. One survivor did not attend the examinations but completed the questionnaires.…”

Section: Participantsmentioning

confidence: 99%

“…Cutoff scores on the BDI-21 did not indicate a significant difference in depressive symptoms between survivors and the control group. 14 …”

Section: Participantsmentioning

confidence: 99%

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Sexual function in male long‐term survivors of childhood acute lymphoblastic leukemia

Haavisto

Henriksson

Heikkinen

et al. 2016

Cancer

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BACKGROUND: Infertility, poor semen quality, and gonadal dysfunction are well recognized long-term sequelae in male survivors of childhood acute lymphoblastic leukemia (ALL). However, few studies have investigated adult sexual functioning in these survivors. METHODS: The authors studied 52 male survivors of childhood ALL at a median age of 28.5 years (range, 25-38 years) 10 years after diagnosis. In addition, 56 men without a history of cancer were recruited for an age-matched control group. The participants completed the Derogatis Interview for Sexual Functioning self-report. To analyze predictive factors for sexual dysfunction, variables assessing sociodemographic background, antileukemia treatment, testicular size, laboratory variables from current serum and semen samples, self-reported depressive symptoms, and self-reported physical functioning were included in multiple regression analyses. RESULTS: ALL survivors had significantly poorer sexual functioning, as measured by the Derogatis Interview for Sexual Functioning self-report, compared with the control group. Survivors had a similar frequency of sexual fantasies, autoerotic acts, and full erection during these activities as the control group, but they had less frequent sexual activity with a sexual partner, poorer self-rated orgasms, and lower satisfaction with their sex life. Predictive factors for poorer sexual functioning were depressive symptoms, the absence of a relationship, and, to a lesser extent, testicular size as an indication of gonadal damage from childhood antileukemia therapy. Older survivors experienced a deeper decline in sexual functioning compared with men in the control group. CONCLUSIONS: Decline in sexual functioning at an early adult age can be regarded as 1 of the late effects of childhood cancer. Monitoring these survivors' sexual health is indicated. Cancer 2016;122:2268-76. V C 2016 American Cancer Society.KEYWORDS: childhood leukemia, late effects, long-term survivors, predictive factors, sexual function. INTRODUCTIONLong-term male survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for impaired fertility, poor semen quality, and gonadal dysfunction because of gonadotoxic treatments, such as testicular irradiation and high cumulative doses of cyclophosphamide, used as part of their antileukemia therapy.1-4 The use of prophylactic cranial irradiation as a part of ALL therapy is associated with a risk of anterior pituitary dysfunction. Gonadotropin deficiency is associated with cranial irradiation at doses of >22 grays (Gy). If untreated, it is known to cause increased risk of abdominal obesity, hypertension, dyslipidemia, low bone mineral density, low energy expenditure, and slow walking.5 During the latest decades, cranial irradiation has largely been omitted from the treatment of ALL, 6 and alkylating agents have decreasingly been used. To a certain extent, this has reduced the risks among leukemia survivors. However, few studies have paid attention to adult sexual functioning and its determinants among long...

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Section: Discussionmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

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Sexual function in male long‐term survivors of childhood acute lymphoblastic leukemia

Haavisto

Henriksson

Heikkinen

et al. 2016

Cancer

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“…Adult male long-term (>10 years) ALL survivors who were born in 1980 or earlier and had been treated at the Children's Hospital, Helsinki University Central Hospital, in 1970-1998 were identified through hospital records and invited to participate in a study assessing reproductive and bone health, related parameters as well as overall wellbeing, and marital, educational and employment status at adult age, as described earlier [18,19,20]. Of the total patient population (n = 164), 75 male long-term survivors were identified and contacted.…”

Section: Methodsmentioning

confidence: 99%

Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia

Jahnukainen¹,

Heikkinen²,

Henriksson³

et al. 2015

Horm Res Paediatr

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Background: We evaluated the body composition and its association with hypogonadism in adult male long-term acute lymphoblastic leukemia (ALL) survivors. Methods: The cohort included 49 long-term male ALL survivors and 55 age-matched healthy controls. Fat and lean mass was assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for adipokines and testicular endocrine markers. Results: As compared with controls, the ALL survivors (median age 29 years, range 25-38), assessed 10-28 years after ALL diagnosis, had higher percentages of body (p < 0.05) and trunk fat mass (p < 0.05), and a lower body lean mass (p < 0.001). Survivors had significantly higher levels of leptin and adiponectin and lower levels of insulin-like growth factor-binding protein 3. Body fat mass and percent fat mass correlated with serum leptin and sex hormone-binding globulin (SHBG) levels. Altogether, 15% of the ALL survivors and 9% of age-matched controls were obese (BMI ≥30). Obese survivors more often had hypogonadism, had received testicular irradiation, and needed testosterone replacement therapy compared to nonobese survivors. Conclusion: At young adulthood, long-term male ALL survivors have significantly increased body adiposity despite normal weight and BMI. Potential indicators of increased adiposity included high leptin and low SHBG levels. Serum testicular endocrine markers did not correlate with body adiposity.

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“…30–33 In light of an anticipated growing number of survivors of ITR and ALL relapse in general, consideration of significant late effects potentially impacting quality of life should be considered seriously in the decision regarding treatment. 34,35 …”

Section: Introductionmentioning

confidence: 99%

Isolated late testicular relapse of B‐cell acute lymphoblastic leukemia treated with intensive systemic chemotherapy and response‐based testicular radiation: A Children's Oncology Group study

Barredo

Hastings²,

et al. 2017

Pediatric Blood & Cancer

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Background The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5-year overall survival (OS). This study aimed to improve outcome in patients with ITR of B-cell ALL (B-ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long-term sequelae by limiting use of testicular radiation. Procedure Forty patients in first ITR of B-ALL were enrolled. Induction (dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy) was preceded by one dose of high-dose methotrexate (MTX, 5 g/m2). Following induction, 25 of 26 patients who had persistent testicular enlargement underwent testicular biopsy. Eleven had biopsy-proven disease and received bilateral testicular radiation (24 Gy), whereas twenty-nine did not. Results Overall 5-year event-free survival (EFS)/OS was 65.0 ± 8.8%/73.1 ± 8.3%, with 5-year EFS 62.1±11.0% vs. 72.7±14.4% for patients who did not receive radiation therapy (XRT) (n=29) compared with those who did (n = 11), respectively (P = 0.64). There were six second bone marrow relapses and six second ITRs. The proportion of second relapses was similar in the patients that received testicular radiation and those who did not. However, the 5-year OS was similar for patients who did not receive XRT (72.6 ± 10.2%) compared with those who did (72.7 ± 14.4%) (P = 0.85). Conclusions A 5-year OS rate of 73.1 ± 8.3% was obtained in children with first ITR of B-ALL occurring after 18 months of CR1 (length of first clinical remission) using intensive chemotherapy and limiting testicular radiation.

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Potential gonadotoxicity of treatment in relation to quality of life and mental well-being of male survivors of childhood acute lymphoblastic leukemia

Abstract: In general, more attention should be paid for physical functioning of childhood ALL survivors. Increased focus should also be on QOL and mental well-being of survivors with more gonadotoxic treatment modalities and those whose diagnosis was made in their adolescence.

Cited by 17 publications

References 25 publications

Sexual function in male long‐term survivors of childhood acute lymphoblastic leukemia

Sexual function in male long‐term survivors of childhood acute lymphoblastic leukemia

Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia

Isolated late testicular relapse of B‐cell acute lymphoblastic leukemia treated with intensive systemic chemotherapy and response‐based testicular radiation: A Children's Oncology Group study

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